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T OXICOLOGIC PATHOLOGY , vol 29, no 6, pp 639– 652, 2001 Copyright C 2001 by the Society of Toxicologic Pathology Laboratory Animal & Molecular Pathology REVIEW ARTICLE Compendium of Chemical Carcinogens by Target Organ: Results of Chronic Bioassays in Rats, Mice, Hamsters, Dogs, and Monkeys LOIS SWIRSKY GOLD, 1,2 NEELA B. MANLEY, 1 THOMAS H. SLONE, 1 AND JERROLD M. WARD 3 1 Division of Biochemistry and Molecular Biology, University of California, Berkeley, California 94720-320 2 2 Life Sciences Division, Mail Stop: 946, Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, California 94720, and 3 Veterinary and Tumor Pathology Section, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201 ABSTRACT A compendium of carcinogenesi s bioassay results organized by target organ is presented for 738 chemicals that are carcinogenic in chronic-exposure , long-term bioassays in at least 1 species. This compendium is based primarily on experiments in rats or mice; results in hamsters, monkeys , and dogs are also reported. The compendium can be used to identify chemicals that induce tumors at particular sites and to determine whether target sites are the same for chemicals positive in more than 1 species. The source of information is the Carcinogenic Potency Database (CPDB), which includes results of 6073 experiments on 1458 chemicals (positive or negative for carcinogenicity) that have been reported in Technical Reports of the National Cancer Institute/National Toxicology Program or in papers in the general published literature. The published CPDB includes detailed analyses of each test and citations. The CPDB is publicly available in several formats (http://potency.berkeley.edu). Chemical carcinogens are reported for 35 different target organs in rats or mice. Target organs in humans are also summarized for 82 agents that have been evaluated as human carcinogens at a particular target site by the International Agency for Research on Cancer (IARC). Comparisons are provided of target organs for mutagens versus nonmutagens and rats versus mice. Keywords. Human carcinogen; tumor site; animal cancer test; Carcinogenic Potency Database; species comparisons ; mutagenicity; monkeys. INTRODUCTION For many research issues in carcinogenesis, it is valuable to have quick access to a list of chemicals that have been found in chronic bioassays to induce tumors at each target site in various species. Researchers interested in carcinogenesis in a particular target organ, for example, or epidemiologists inter- ested in a particular cancer in humans, can use such results to compare species or seek clues in animal models. Comparison of target sites in several species is possible for work on in- terspecies extrapolation. Investigations of chemical structure or mechanism of carcinogenesis at a speci c target site can identify chemicals that induce tumors in that organ. This paper presents a compendium of results of chronic, long-term cancer tests that is organized by the target or- gan of carcinogenesis (Table 1). Results are presented for 738 chemicals that have been evaluated by the published author of experimental data as carcinogenic in at least one experiment in the Carcinogenic Potency Database (CPDB) (2, 3, 6), http://potency.berkeley.edu/database.html. Results are organized by each of 35 target sites and within each Address correspondenc e to: Lois Swirsky Gold, Mail Stop 946, E. O. Lawrence Berkeley National Laboratory, Berkeley, California 94720. Fax: (510) 547-7073. E-mail: [email protected] site by the chemicals that induce tumors in each species. The compendium includes results of chronic bioassays in rats, mice, hamsters, monkeys, and dogs. Comparative tox- icological analyses are facilitated by indicating whether a chemical that is positive at a given site in the rat has been tested in the mouse, whether results are also positive in the mouse, and whether the target organs are the same in the 2 species. By cross-referencing a chemical of interest to the published plots of the CPDB (2, 3, 6), details of each experiment can be obtained, including the number of ex- periments and strains tested as well as the following details on each experiment: citation of the original published paper, strain and sex of test animal, route of chemical administra- tion, dose rate, tumor types, tumor incidence, the tumorigenic potency (TD 50 ), statistical signi cance, and author’s opinion. Target organs in humans are also summarized for 82 agents that have been evaluated as human carcinogens at a particular target site by the International Agency for Research on Cancer (IARC) (10, 15, 16). Comparisons of target organs for muta- gens versus nonmutagens, and for rats versus mice are also provided. METHODS The CPDB (2, 3, 6), a systematic and unifying analysis of chronic, long-term animal cancer tests, is the source of 639 0192-6233/01$3.00 $0.00

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Page 1: Compendium of Chemical Carcinogens by Target Organ - Toxnet

TOXICOLOGIC PATHOLOGY vol 29 no 6 pp 639ndash652 2001Copyright C 2001 by the Society of Toxicologic Pathology

Laboratory Animal amp Molecular Pathology

REVIEW ARTICLE

Compendium of Chemical Carcinogens by Target OrganResults of Chronic Bioassays in Rats Mice Hamsters Dogs and Monkeys

LOIS SWIRSKY GOLD12 NEELA B MANLEY1 THOMAS H SLONE1 AND JERROLD M WARD3

1Division of Biochemistry and Molecular Biology University of California Berkeley California 94720-32022Life Sciences Division Mail Stop 946 Ernest Orlando Lawrence Berkeley National Laboratory Berkeley California 94720 and

3Veterinary and Tumor Pathology Section Center for Cancer Research National Cancer Institute Frederick MD 21702-1201

ABSTRACT

A compendium of carcinogenesi s bioassay results organized by target organ is presented for 738 chemicals that are carcinogenic in chronic-exposure long-term bioassays in at least 1 species This compendium is based primarily on experiments in rats or mice results in hamsters monkeys and dogsare also reported The compendium can be used to identify chemicals that induce tumors at particular sites and to determine whether target sites arethe same for chemicals positive in more than 1 species The source of information is the Carcinogenic Potency Database (CPDB) which includesresults of 6073 experiments on 1458 chemicals (positive or negative for carcinogenicity) that have been reported in Technical Reports of the NationalCancer InstituteNational Toxicology Program or in papers in the general published literature The published CPDB includes detailed analyses of eachtest and citations The CPDB is publicly available in several formats (httppotencyberkeleyedu) Chemical carcinogens are reported for 35 differenttarget organs in rats or mice Target organs in humans are also summarized for 82 agents that have been evaluated as human carcinogens at a particulartarget site by the International Agency for Research on Cancer (IARC) Comparisons are provided of target organs for mutagens versus nonmutagensand rats versus mice

Keywords Human carcinogen tumor site animal cancer test Carcinogenic Potency Database species comparisons mutagenicity monkeys

INTRODUCTION

For many research issues in carcinogenesis it is valuableto have quick access to a list of chemicals that have been foundin chronic bioassays to induce tumors at each target site invarious species Researchers interested in carcinogenesis in aparticular target organ for example or epidemiologists inter-ested in a particular cancer in humans can use such results tocompare species or seek clues in animal models Comparisonof target sites in several species is possible for work on in-terspecies extrapolation Investigations of chemical structureor mechanism of carcinogenesis at a speci c target site canidentify chemicals that induce tumors in that organ

This paper presents a compendium of results of chroniclong-term cancer tests that is organized by the target or-gan of carcinogenesis (Table 1) Results are presented for738 chemicals that have been evaluated by the publishedauthor of experimental data as carcinogenic in at least oneexperiment in the Carcinogenic Potency Database (CPDB)(2 3 6) httppotencyberkeleyedudatabasehtml Resultsare organized by each of 35 target sites and within each

Address correspondenc e to Lois Swirsky Gold Mail Stop 946 E OLawrence Berkeley National Laboratory Berkeley California 94720 Fax(510) 547-7073 E-mail loispotencyberkeleyedu

site by the chemicals that induce tumors in each speciesThe compendium includes results of chronic bioassays inrats mice hamsters monkeys and dogs Comparative tox-icological analyses are facilitated by indicating whether achemical that is positive at a given site in the rat has beentested in the mouse whether results are also positive inthe mouse and whether the target organs are the same inthe 2 species By cross-referencing a chemical of interest tothe published plots of the CPDB (2 3 6) details of eachexperiment can be obtained including the number of ex-periments and strains tested as well as the following detailson each experiment citation of the original published paperstrain and sex of test animal route of chemical administra-tion dose rate tumor types tumor incidence the tumorigenicpotency (TD50) statistical signi cance and authorrsquos opinionTarget organs in humans are also summarized for 82 agentsthat have been evaluated as human carcinogens at a particulartarget site by the International Agency for Research on Cancer(IARC) (10 15 16) Comparisons of target organs for muta-gens versus nonmutagens and for rats versus mice are alsoprovided

METHODS

The CPDB (2 3 6) a systematic and unifying analysisof chronic long-term animal cancer tests is the source of

639 0192-623301$300 $000

640 GOLD ET AL TOXICOLOGIC PATHOLOGY

results included in the compendium (Table 1) The CPDBincludes 1381 papers published in the general literaturethrough 1996 and 430 Technical Reports of the NationalCancer InstituteNational Toxicology Program (NCINTP)published through 1998 Results are reported for 6073 ex-periments on 1458 chemicals of which 738 induce tumorsin 1 or more experiments

A word of caution is necessary about the limitations ofthe CPDB Only long-term experiments meeting a set of cri-teria designed to measure tumorigenic dose-rate (TD50) areincluded therefore the CPDB does not cover all cancer testsAdditionally for the identi cation of target sites for the com-pendium we do not personally evaluate whether a compoundinduced tumors at a given site rather the opinion of the pub-lished author is used For published opinions that are notclear even after personal communication with the publishedauthor the site is not considered a target and is not reportedin the compendium

Results of all NCINTP Technical Reports are included inthe CPDB except a few for which no whole body exposure inmgkgday could be calculated because the test agent was aparticulate or the route of administration was dermal (12 13)[httpntp-serverniehsnihgov] In the compendium a siteis classi ed as a target in an NCINTP bioassay if the eval-uation in the Technical Report was ldquocarcinogenicrdquo ldquoclearrdquoor ldquosomerdquo evidence of carcinogenic activity Sites that wereevaluated as ldquoequivocalrdquo are not included (9)

In the general literature experimental designs as well asthe authorsrsquo choice of information to report are quite diverseand bioassays have been included only if they meet all of thefollowing conditions

1 Animals on test were mammals2 Administration was begun early in life (100 days of age

or less for rats mice and hamsters)3 Route of administration was diet water gavage inhala-

tion intravenous or intraperitoneal injection (ie wherethe whole body was more likely to have been exposedrather than only a speci c site as with subcutaneous in-jection or skin painting)

4 Test agent was administered alone rather than in combi-nation with other chemicals

5 Exposure was chronic with not more than 7 days betweenadministrations

6 Duration of exposure was at least one fourth the standardlife span for that species For rodents the standard lifespan is 2 years

7 Duration of experiment was at least half the standard lifespan for that species

8 Research design included a concurrent control group9 Research design included at least 5 animals per group

10 Surgical intervention was not performed11 Pathology data were reported for the number of animals

with tumors rather than the total number of tumors12 Results reported were original data rather than sec-

ondary analyses of experiments already reported by otherauthors

More details on inclusion criteria can be found in Goldand coworkers (6) and httppotencyberkeleyedutextmethodshtml

Because we have adhered strictly to the standard inclu-sion criteria bioassays of particulate or brous matters arenot in the compendium eg asbestos cigarette smoke anddusts There are no studies using a single administration ofthe test agent no experiments by skin painting subcutaneousinjection or in utero exposure and no cocarcinogenesis ex-periments For a series of NCI long-term studies in monkeyssome of the inclusion rules have been relaxed details arereported in Appendix 1 of Gold et al 1999 (2)

There is great diversity in results for different chemicalsin the CPDB eg in the number of times a chemical has beentested among the 1148 chemicals tested in rats 25 haveonly 1 test in the CPDB and 50 have 2 tests however25 chemicals have 10 or more tests For the 938 chemicalstested in mice the parallel numbers are 11 with 1 test 57with 2 tests and 15 chemicals with more than 10 tests Ofthe 738 carcinogens reported here 54 (397738) have beentested in more than 1 species In the compendium (Table 1)a target site is identi ed by a positive result in any one ex-periment in the species thus different target sites may beidenti ed from the same or different experiments Chemi-cals that are tested more often have a greater chance of nd-ing multiple target sites Results on chemicals that have notbeen evaluated as carcinogenic are ignored in the target or-gan compendium (Table 1) however detailed results of thoseexperiments are reported in the plot of the CPDB (2 3 6)httppotencyberkeleyedu

Guide to the Compendium of Target Organs for 738Carcinogens

Table 1 reports results on 738 chemicals in the CPDB thatinduce tumors in at least 1 of 35 target organs in rats micehamsters monkeys or dogs The table is organized alpha-betically by target site and within each site by species andchemical Our previously unpublished analyses of experi-mental results that will be published in a forthcoming plot ofthe CPDB are included (3)

To facilitate use of the compendium the features aredescribed below using the example of adrenal gland whichis the rst of 35 target sites in Table 1 Under adrenal gland1 chemical is listed in hamsters 8 in mice and 16 in ratsIf a chemical name is followed by a superscript (either yor z) this indicates that the CPDB includes test results inboth rats and mice for example under adrenal gland in rats2-mercaptobenzothiazole but not isomazole has a super-script Because isomazole has no superscript it only hastests in the CPDB in the species reported in this case ratsThe superscript y for 2-mercaptobenzothiazole indicatesthat the chemical has been tested in both rats and mice butinduced tumors only in the reported species in this case ratsThe superscript z for 12-dibromo-3-chloropropane (DBCP)indicates that DBCP is carcinogenic at some target site inboth rats and mice Although the superscript z does not indi-cate whether DBCP induced tumors at the same target site inboth rats and mice this can easily be determined by lookingat mice under adrenal gland for the chemical name DBCPBecause it is not there DBCP induced tumors in mice only atsites other than the adrenal gland In contrastpentachloroanisole z induced adrenal tumors in both speciesbeacuse it is listed under that site for both species Bycomparing the chemicals with superscripts listed under each

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Adr

enal

glan

dH

amst

er1

Ure

than

ez

Mou

se8

Car

bon

tetr

achl

orid

ez F

uran

z 4

4-M

ethy

lene

dian

iline

2H

Clz

Pen

tach

loro

anis

olez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y

23

45

6-P

enta

chlo

roph

enol

tec

hnic

algr

adez

p-R

osan

ilin

eH

Clz

11

2-T

rich

loro

etha

ney

Rat

16B

rom

oeth

anez

4-C

hlor

o-m

-phe

nyle

nedi

amin

ez C

obal

tsul

fate

hept

ahyd

rate

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

Die

thyl

stilb

estr

olz

Eth

ylal

coho

ly In

dolid

anI

som

azol

e2-

Mer

capt

oben

zoth

iazo

ley

Mir

exz

Pen

tach

loro

anis

olez

Phe

nolp

htha

lein

z 1

2-Pr

opyl

ene

oxid

ez C

Ip

igm

entr

ed3z

Res

erpi

nez

Ret

inol

acet

ate

Bon

eR

at5

Acr

onyc

ine

De

azac

ort

NN

-Dim

ethy

lani

liney

1-( 2

-Hyd

roxy

ethy

l)-1

-nit

roso

urea

z o-

Tolu

idin

eH

Clz

Clit

oral

pre

putia

lM

ouse

11A

ceta

ldeh

yde

met

hylf

orm

ylhy

draz

one

Ben

zene

z 1

3-B

utad

iene

z N

-n-B

utyl

-N-f

orm

ylhy

draz

ine

Dim

ethy

lvin

ylch

lori

dez

N-E

thyl

-N-f

orm

ylhy

draz

ine

glan

dH

exan

alm

ethy

lfor

myl

hydr

azon

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eP

enta

nalm

ethy

lfor

myl

hydr

azon

eN

-N-P

ropy

l-N

-for

myl

hydr

azin

eT

hio-

tepa

z

Rat

21A

cryl

amid

eC

Id

irec

tblu

e15

24

-Dia

min

oani

sole

sulf

atez

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

Glu

-P-1

z G

lu-P

-2z

Gly

cido

lz IQ

z Is

opho

rone

y M

eIQ

xz 2-

Mer

capt

oben

zoth

iazo

ley

Nal

idix

icac

idy

15-

Nap

htha

lene

diam

inez

5-N

itro-

o-a

nisi

dine

z 5-

Nit

roac

enap

hthe

nez

p-N

itro

benz

oic

acid

y 1-

Nitr

opyr

ene

CI

aci

dre

d11

41

23-

Tri

chlo

ropr

opan

ez T

rp-P

-2ac

etat

ez

Ear

Zym

balrsquos

glan

dM

ouse

3B

enze

nez

Chl

orop

rene

z C

upfe

rron

z

Rat

41A

cryl

onit

rile

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

Azo

xym

etha

neB

enze

nez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

irec

tblu

e15

N-n

-But

yl-N

-nitr

osou

rea

Chl

oram

buci

lz C

upfe

rron

z N

-1-D

iace

tam

ido

uore

ne2

4-D

iam

inoa

niso

lesu

lfat

ez 3

3-D

ichl

orob

enzi

dine

25

-Dim

etho

xy-4

-am

inos

tilb

enez

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

N-(

2-Fl

uore

nyl)

-22

2-t

riu

oroa

ceta

mid

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

Hyd

razo

benz

enez

IQz

IQH

Cl

MeI

Qxz

2-M

etho

xy-3

-am

inod

iben

zofu

ran

8-M

etho

xyps

oral

enN

-(N

-Met

hyl-

N-n

itro

soca

rbam

oyl)

-l-o

rnit

hine

44

-Met

hyle

ne-

bis(

2-ch

loro

anili

ne)

5-N

itro-

o-an

isid

inez

5-N

itroa

cena

phth

enez

N-(

9-O

xo-2

-uo

reny

l)ac

etam

ide

Phen

acet

inz

Pre

dnim

usti

neC

Ia

cid

red

114

p-R

osan

iline

HC

lz T

hio-

tepa

z 4

4-T

hiod

iani

line

z b

-Thi

ogua

nine

deox

yrib

osid

e1

23-

Tri

chlo

ropr

opan

ez V

inyl

chlo

ride

z V

inyl

uor

idez

Eso

phag

usH

amst

er2

AF-

2z N

-Nitr

oso-

N-m

ethy

lure

than

eM

ouse

8B

enzo

( a) p

yren

ez 1

2-D

ibro

moe

than

ez N

-Eth

yl-N

-nit

ro-N

-nit

roso

guan

idin

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

3-( 5

-Nit

ro-2

-fur

yl) -

imid

azo(

12-

a) p

yrid

inez

Nitr

osod

ibut

ylam

inez

N-N

itros

ohex

amet

hyle

neim

ine

Vin

ylac

etat

ez

Mon

key

1N

-Nitr

oso-

N-m

ethy

lure

az

Rat

362

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

N-n

-But

yl-N

-nitr

osou

rea

Dih

ydro

safr

olez

Dim

ethy

lvin

ylch

lori

dez

Din

itro

soho

mop

iper

azin

eZ

-Eth

yl-O

NN

-azo

xyet

hane

N-M

ethy

l-N

-nitr

o-N

-nit

roso

guan

idin

ez 3-

( 5-N

itro

-2-f

uryl

) -im

idaz

o(1

2-a

) pyr

idin

ez N

-Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-hy

drox

ypro

pyla

min

eN

itro

so-2

3-d

ihyd

roxy

prop

yl-2

-oxo

prop

ylam

ine

N-N

itro

so-(

2-hy

drox

ypro

pyl)

-(2-

hydr

oxye

thyl

) am

ine

N-N

itros

o-N

-met

hyl-

4-u

oroa

nilin

eN

itros

o-N

-met

hyl-

N-(

2-ph

enyl

) eth

ylam

ine

Nitr

oso-

12

36-

tetr

ahyd

ropy

ridi

neN

-Nit

roso

( 22

2-t

riu

oroe

thyl

) eth

ylam

ine

N-N

itros

oall

yl-2

3-d

ihyd

roxy

prop

ylam

ine

N-N

itro

soal

lyl-

2-hy

drox

ypro

pyla

min

eN

-Nit

roso

ally

l-2-

oxop

ropy

lam

ine

Nitr

osoa

myl

uret

han

Nitr

osoa

naba

sine

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

ipro

pyla

min

eN

itro

soet

hylu

reth

ane

Nit

roso

hept

amet

hyle

neim

ine

N-N

itro

som

ethy

l-2

3-di

hydr

oxyp

ropy

lam

ine

N-N

itros

omet

hyl-

2-hy

drox

ypro

pyla

min

eN

-Nit

roso

met

hyl(

2-ox

opro

pyl)

amin

e2-

Nitr

osom

ethy

lam

inop

yrid

ine

Nit

roso

met

hyla

nili

neN

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oson

orni

cotin

e-1-

N-o

xide

N-N

itro

sopi

peri

dine

z N

-Nit

roso

thia

ldin

eN

-Nit

roso

thio

mor

phol

ine

Gal

lbla

dder

Ham

ster

1N

-Met

hyl-

N-f

orm

ylhy

draz

ine

Mou

se4

N-E

thyl

-N-f

orm

ylhy

draz

ine

N-M

ethy

l-N

-for

myl

hydr

azin

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eN

-N-P

ropy

l-N

-for

myl

hydr

azin

eM

onke

y1

Aa

toxi

nB

y 1H

arde

rian

glan

dM

ouse

19B

enze

nez

Ben

zidi

ne2

HC

l2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

13-

But

adie

nez

Cap

tafo

lz C

hlor

opre

nez

Cup

ferr

onz

Dic

hlor

oace

tyle

nez

Eth

ylen

eox

idez

Gen

tian

viol

etG

lyci

dolz

Iodi

nate

dgl

ycer

olz

Isop

rene

N-M

ethy

lola

cryl

amid

ey N

itro

met

hane

z 4

4-O

xydi

anil

inez

12

3-T

rich

loro

prop

anez

24

6-T

rini

tro-

13-

dim

ethy

l-5-

tert

-but

ylbe

nzen

eV

inyl

uor

idez

Hem

atop

oiet

icM

ouse

53A

ceta

mid

ez A

at

oxin

cru

dez

Ally

liso

vale

rate

z tr

ans-

5-A

min

o-3[

2-( 5

-nitr

o-2-

fury

l)vi

nyl] -

12

4-ox

adia

zole

2-A

min

o-4-

( p-n

itro

phen

yl) t

hiaz

ole

syst

em2-

Am

inoa

nthr

aqui

none

z 5-

Aza

cyti

dine

z A

zath

iopr

ine

Ben

zene

z 1

4-B

enzo

quin

one

Ben

zotr

ichl

orid

eB

enzo

ylhy

draz

ine

13-

But

adie

nez

12-

di-n

-But

ylhy

draz

ine

2HC

lC

apta

folz

Chl

oram

buci

lz C

hlor

inat

edpa

raf

ns( C

234

3ch

lori

ne)y

Cyc

loph

osph

amid

ez D

acar

bazi

nez

DD

Tz

Dib

rom

odul

cito

lz D

ibro

mom

anni

tolz

Est

radi

olm

usta

rdy

Eth

ylen

eox

idez

5-Fl

uoro

urac

ily Fo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

entia

nvi

olet

Hex

anam

idey

2-H

ydra

zino

-4-(

p-am

inop

heny

l)th

iazo

lez

2-H

ydra

zino

-4-

( p-n

itro

phen

yl) t

hiaz

olez

1-( 2

-Hyd

roxy

ethy

l)-1

-nit

roso

urea

z IC

RF

-159

z Is

opho

spha

mid

ez Is

opre

neM

eIQ

xz M

elph

alan

z 1-

Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

mM

ethy

lmet

hane

sulf

onat

e4

4-M

ethy

lene

dian

ilin

e2H

Clz

Met

roni

dazo

lez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hene

ster

inz

Phe

nolp

htha

lein

z Ph

IPH

Clz

Phor

bol

Proc

arba

zine

HC

lz S

trob

ane

Tetr

auo

roet

hyle

nez

Thi

o-te

paz

p-To

lylu

reay

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez U

reth

anez

CI

vat

yello

w4y

( Con

tinue

don

next

page

)

641

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Mon

key

1P

roca

rbaz

ine

HC

lz

Rat

56A

llyl

isov

aler

atez

1-A

myl

-1-n

itros

oure

aA

traz

iney

Ben

zidi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

CI

dir

ectb

lue

15

N-n

-But

yl-N

-nitr

osou

rea

Cad

miu

mch

lori

deC

hlor

ambu

cilz

Cyc

loph

osph

amid

ez D

acar

bazi

nez

13-

Dib

utyl

-1-n

itro

sour

eaD

ichl

oroa

cety

lene

z 3

3-D

ichl

orob

enzi

dine

Dic

hlor

vosz

Dim

etho

xane

33

-Dim

etho

xybe

nzid

ine-

44

-dii

socy

anat

ey 3

3-D

imet

hoxy

benz

idin

e2H

Cl

Dim

ethy

lmor

phol

inop

hosp

hora

mid

atey

2-( 2

2-D

imet

hylh

ydra

zino

) -4-

( 5-n

itro-

2-fu

ryl)

thia

zole

Eth

ylen

eox

idez

Form

alde

hyde

z Fo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z F

uran

z G

lyci

dolz

FD

ampC

gree

nno

1y

FDamp

Cgr

een

no2

y H

emat

oxyl

in2

-Hyd

razi

no-4

-(p-

amin

ophe

nyl)

thia

zole

z H

ydro

quin

onez

1-( 2

-Hyd

roxy

ethy

l)-1

-nit

roso

urea

z Io

dina

ted

glyc

erol

z L

asio

carp

ine

2-M

erca

ptob

enzo

thia

zole

y M

etep

aM

ethy

lter

t-bu

tyle

ther

z M

irex

z l-

5-M

orph

olin

omet

hyl-

3-[(

5-ni

trof

urfu

ryli

dene

) am

ino]

-2-o

xazo

lidi

none

H

Cl

Nit

rite

sod

ium

y N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez o-

Nit

roan

isol

ez 1-

[(5-

Nitr

ofur

fury

liden

e)am

ino]

-2-i

mid

azol

idin

one

1-N

itro

pyre

neN

itros

o-N

-met

hyl-

N-(

2-ph

enyl

) eth

ylam

ine

N-N

itros

odie

than

olam

ine

PhIP

HC

lz P

roca

rbaz

ine

HC

lz P

ropa

nesu

ltone

N-P

ropy

l-N

-nit

roso

urea

FD

ampC

red

no2

FD

ampC

red

no4

y Te

trac

hlor

oeth

ylen

ez Te

tra

uoro

ethy

lene

z T

hio-

tepa

z 2

46-

Tri

chlo

roph

enol

z T

rp-P

-2ac

etat

ez

Kid

ney

Ham

ster

1B

rom

ate

pota

ssiu

mz

Mou

se26

o-B

enzy

l-p-

chlo

roph

enol

y 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z B

rom

odic

hlor

omet

hane

z 1

3-B

utad

iene

z 1

2-di

-n-B

utyl

hydr

azin

e2H

Cl

Caf

feic

acid

z C

hlor

ofor

mz

Chl

orop

rene

z D

amin

ozid

ez 2

4-D

iam

inop

heno

l2H

Cly

Dic

hlor

oace

tyle

nez

24-

Din

itrot

olue

ne( c

onta

inin

g1

0-1

52

6-di

nitr

otol

uene

)zH

ydro

quin

onez

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z 3-

Hyd

roxy

-p-b

utyr

ophe

neti

dide

L

ead

acet

ate

basi

cz M

ercu

rym

ethy

lchl

orid

eN

itril

otri

acet

icac

idz

Och

rato

xin

Az

Phe

nace

tinz

CI

pig

men

tred

3z St

rept

ozot

ocin

z T

ris(

2-ch

loro

ethy

l)ph

osph

atez

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez V

inyl

iden

ech

lori

dey

Mon

key

1C

ycas

inan

dm

ethy

lazo

xym

etha

nola

ceta

teR

at86

A

atox

inB

1y 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 1-

Am

ino-

2-m

ethy

lant

hraq

uino

nez

2-A

min

o-5-

( 5-n

itro-

2-fu

ryl)

-13

4-o

xadi

azol

e2-

Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

e2-

Am

ino-

4-ni

trop

heno

ly 2-

Am

ino-

5-ni

trot

hiaz

oley

o-A

nisi

dine

HC

lz A

rist

oloc

hic

acid

so

dium

salt

( 77

AA

I21

A

AII

) A

zoxy

met

hane

Bar

bita

lso

dium

Ben

zofu

ranz

Bro

mat

epo

tass

ium

z B

rom

odic

hlor

omet

hane

z te

rt-B

utyl

alco

holz

Caf

feic

acid

z C

apta

folz

Cap

tanz

Chl

orin

ated

para

fns

( C12

60

chlo

rine

)zC

hlor

ofor

mz

3-( p

-Chl

orop

heny

l)-1

1-d

imet

hylu

reay

Chl

orop

rene

z C

hlor

otha

loni

ly C

inna

myl

anth

rani

late

z C

itrin

inC

oum

arin

z D

ichl

oroa

cety

lene

z 1

4-D

ichl

orob

enze

nez

Die

thyl

acet

amid

e3

4-D

ihyd

roco

umar

inz

Dim

etho

xane

Dim

ethy

lmet

hylp

hosp

hona

tey

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

N-4

-(4

-Flu

orob

iphe

nyl)

acet

amid

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lyci

neH

exac

hlor

obut

adie

ne

Hex

achl

oroe

than

ez H

exam

ethy

lmel

amin

e2-

Hyd

razi

no-4

-(5-

nitr

o-2-

fury

l)th

iazo

lez

Hyd

roqu

inon

ez 1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

Isop

horo

ney

Lea

dac

etat

ey L

ead

acet

ate

basi

cz d-

Lim

onen

ey 2-

Met

hoxy

-3-a

min

odib

enzo

fura

n8-

Met

hoxy

psor

alen

Z-M

ethy

l-O

NN

-azo

xyet

hane

Met

hylt

ert-

buty

leth

erz

N-(

N-M

ethy

l-N

-nit

roso

carb

amoy

l)-l

-orn

ithi

nea

-Met

hylb

enzy

lalc

ohol

y M

irex

z l-

5-M

orph

olin

omet

hyl-

3-[(

5-ni

trof

urfu

rylid

ene)

amin

o]-2

-oxa

zolid

inon

eH

Cl

Nit

rilo

tria

ceti

cac

idz

Nit

rilo

tria

cetic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

3-( 5

-Nitr

o-2-

fury

l)-i

mid

azo(

12-

a) p

yrid

inez

N-[

3-( 5

-Nitr

o-2-

fury

l)-1

24

-oxa

diaz

ole-

5-yl

] -m

ethy

l]ac

etam

ide

N-[

5-( 5

-Nitr

o-2-

fury

l)-1

34

-thi

adia

zol-

2-yl

] ace

tam

idez

o-N

itro

anis

olez

Nitr

oben

zene

z 2-

Nit

ro

uore

ne

1-[(

5-N

itrof

urfu

rylid

ene)

amin

o]hy

dant

oinz

1-N

itro

so-1

-hyd

roxy

ethy

l-3-

chlo

roet

hylu

rea

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

imet

hyla

min

ez N

-Nit

roso

pyrr

olid

inez

Och

rato

xin

Az

CI

aci

dor

ange

3y N

-Oxy

diet

hyle

neth

ioca

rbam

yl-N

-oxy

diet

hyle

nesu

lfen

amid

eP

hena

cetin

z Ph

enaz

one

Phen

olph

thal

einz

Phen

ylbu

tazo

nez

o-Ph

enyl

phen

ate

sodi

umy

Que

rcet

iny

Salic

ylaz

osul

fapy

ridi

nez

Str

epto

zoto

cinz

Tetr

achl

oroe

thyl

enez

Tetr

auo

roet

hyle

nez

Tetr

ahyd

rofu

ranz

12

3-T

rich

loro

prop

anez

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylch

lori

dez

Lar

gein

test

ine

Ham

ster

51

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

Hyd

razi

nez

Met

hylh

ydra

zine

Ure

than

ezM

ouse

1C

apsa

icin

Rat

32A

at

oxin

B1y

1-A

llyl

-1-n

itros

oure

a1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z A

myl

opec

tin

sulf

ate

Azo

xym

etha

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

te

chni

calg

rade

z C

Id

irec

tblu

e15

Bro

mod

ichl

orom

etha

nez

N-N

-But

yl-n

-nitr

osou

rea

Car

rage

enan

aci

d-de

grad

edC

hrys

azin

z D

extr

ansu

lfat

eso

dium

( DS-

M-1

) 3

3-D

imet

hoxy

benz

idin

e2H

Cl

33

-Dim

ethy

lben

zidi

ne2

HC

lz Z

-Eth

yl-O

NN

-azo

xym

etha

ne1

-Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

Glu

-P-1

z G

lu-P

-2z

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

IQz

o-N

itro

anis

olez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

Phe

nazo

pyri

dine

HC

lz P

hIP

HC

lz C

Ia

cid

red

114

44

-Thi

odia

nilin

ez T

ribr

omom

etha

ney

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez

Liv

erD

og2

33

-Dic

hlor

oben

zidi

ne4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line

)H

amst

er16

2-A

cety

lam

ino

uore

nez

pp

-DD

Ey

12-

Dim

ethy

lhyd

razi

ne2

HC

lH

exac

hlor

oben

zene

z H

ydra

zine

sulf

atez

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z N

-Met

hyl-

N-f

orm

ylhy

draz

ine

Met

hylh

ydra

zine

Met

hyln

itros

amin

o-N

N-d

imet

hyle

thyl

amin

eN

-Nitr

oso-

13-

oxaz

olid

ine

Nit

roso

-2-o

xopr

opyl

etha

nola

min

eN

-Nitr

osoa

llyl-

2-ox

opro

pyla

min

eN

-Nit

roso

azet

idin

eN

-Nit

roso

mor

phol

ine

N-N

itros

opip

erid

inez

N-N

itros

opyr

rolid

inez

Mou

se23

1A

-a-C

Ace

tam

inop

henz

2-A

cety

lam

ino

uore

nez

Aci

uor

fen

Ald

rinz

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

min

o-2-

met

hyla

nthr

aqui

none

z 2-

Am

inoa

nthr

aqui

none

z 4-

Am

inod

iphe

nyl

2-A

min

odip

heny

lene

oxid

e3-

Am

inot

riaz

olez

Ara

mite

z A

rocl

or12

54y

Aur

amin

e-O

z B

enzi

dine

2H

Cl

Ben

zofu

ranz

Ben

zyla

ceta

tey

3-B

enzy

lsyd

none

-4-a

ceta

mid

ez B

is( 2

-chl

oro-

1-m

ethy

leth

yl) e

ther

tec

hnic

algr

adey

Bis

-2-c

hlor

oeth

ylet

her

Bis

-2-h

ydro

xyet

hyld

ithio

carb

amic

acid

pot

assi

umC

Id

irec

tbla

ck38

CI

dir

ectb

lue

218z

HC

blue

no1

z H

Cbl

ueno

1( p

uri

ed)

Bro

mod

ichl

orom

etha

nez

13-

But

adie

nez

But

ylat

edhy

drox

ytol

uene

y 1

1-di

-n-B

utyl

hydr

azin

eC

apta

folz

Car

bazo

le

Car

bon

tetr

achl

orid

ez C

hlor

alhy

drat

eC

hlor

ambe

ny C

hlor

dane

tec

hnic

algr

adey

Chl

oren

dic

acid

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

1-

Chl

oro-

2-ni

trob

enze

ney

1-C

hlor

o-4-

nitr

oben

zene

y 4-

Chl

oro-

m-p

heny

lene

diam

inez

4-C

hlor

o-o-

phen

ylen

edia

min

ez 5-

Chl

oro-

o-to

luid

iney

642

[ 4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

] ace

ticac

idz

4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

( N-b

-hyd

roxy

ethy

l)ac

etam

idez

Chl

oroa

ceta

ldeh

yde

p-C

hlor

oani

line

HC

lz C

hlor

oben

zila

tey

Chl

orod

ibro

mom

etha

ney

Chl

orof

orm

z C

hlor

opre

nez

Chr

ysaz

inz

CI-

924

Cin

nam

ylan

thra

nila

tez

Cip

ro

brat

ez C

lobu

zari

ty C

ompo

und

LY17

1883

Cou

mar

inz

p-C

resi

dine

z C

upfe

rron

z C

ycla

mat

eso

dium

y C

yclo

chlo

roti

neC

ypro

tero

neac

etat

ep

p-D

DD

y p

p-D

DE

y D

DT

z D

ialla

te2

4-D

iam

inot

olue

nez

24-

Dia

min

otol

uene

2H

Clz

35-

Dic

hlor

o-( N

-11

-dim

ethy

l-2-

prop

ynyl

) ben

zam

ide

26-

Dic

hlor

o-p-

phen

ylen

edia

min

ey D

ichl

oroa

cetic

acid

z 1

4-D

ichl

orob

enze

nez

12-

Dic

hlor

opro

pane

y D

icof

oly

Die

ldri

nz D

ifta

lone

34

-Dih

ydro

coum

arin

z D

ihyd

rosa

frol

ez 2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 1

1-D

imet

hylh

ydra

zine

y 1

4-D

ioxa

nez

55-

Dip

heny

lhyd

anto

iny

Dip

yron

ey D

oxyl

amin

esu

ccin

atez

Est

rago

led

l-E

thio

nine

z o-

Eth

oxyb

enza

mid

eN

-Eth

yl-N

-for

myl

hydr

azin

eE

thyl

ene

imin

eE

thyl

ene

thio

urea

z 2-

Eth

ylhe

xano

ly di

( 2-E

thyl

hexy

l)ad

ipat

ey di

( 2-E

thyl

hexy

l)ph

thal

atez

4-F

luor

o-4-

amin

odip

heny

lF

uran

z Fu

rfur

alz

Gen

tian

viol

etG

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

Gri

seof

ulvi

nH

CD

Dm

ixtu

rez

Hep

tach

lory

Hex

achl

orob

enze

nez

a-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

z b

-12

34

56

-Hex

achl

oroc

yclo

hexa

nec

-12

34

56

-Hex

achl

oroc

yclo

hexa

ney

Hex

achl

oroc

yclo

hexa

ne

tech

nica

lgra

deH

exac

hlor

oeth

anez

Hex

anal

met

hylf

orm

ylhy

draz

one

Hyd

razi

nesu

lfat

ez H

ydra

zobe

nzen

ez H

ydro

quin

onez

N-H

ydro

xy-2

-ac

etyl

amin

ouo

rene

z 1

-Hyd

roxy

estr

agol

e2-

Hyd

roxy

ethy

lhyd

razi

ne1

-Hyd

roxy

safr

olez

IQz

Ison

iazi

dz Is

opre

neK

epon

ez L

eupe

ptin

Lov

asta

tinL

uteo

skyr

inM

alon

alde

hyde

sod

ium

saltz

MeA

-a-C

acet

atez

MeI

QM

eIQ

xz M

ethi

dath

ion

3-M

etho

xy-4

-am

inoa

zobe

nzen

eM

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z N

-Met

hyl-

N-f

orm

ylhy

draz

ine

3-M

ethy

lbut

anal

met

hylf

orm

ylhy

draz

one

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nili

ne)

2HC

ly M

ethy

lene

chlo

ride

z 4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Met

hylh

ydra

zine

N-M

ethy

lola

cryl

amid

ey M

ethy

lphe

nida

teH

Cly

Mic

hler

rsquoske

tone

z M

irex

z 1

5-N

apht

hale

nedi

amin

ez 2-

Nap

hthy

lam

inez

Nit

hiaz

idez

3-N

itro-

p-ac

etop

hene

tidey

5-N

itro-

o-an

isid

inez

2-N

itro

-p-p

heny

lene

diam

iney

5-N

itro

-o-t

olui

dine

y 5-

Nitr

oace

naph

then

ez o-

Nitr

oani

sole

z N

itrob

enze

nez

6-N

itrob

enzi

mid

azol

ey N

itro

fenz

Nit

rom

etha

nez

Nitr

osod

ibut

ylam

inez

N-N

itros

odim

ethy

lam

inez

p-N

itros

odip

heny

lam

inez

N-N

itro

sohe

xam

ethy

lene

imin

eN

-Nit

roso

pipe

ridi

nez

Non

abro

mob

iphe

nyl

Och

rato

xin

Az

Oxa

zepa

my

44

-Oxy

dian

iline

z Pe

ntac

hlor

oeth

aney

Pent

achl

oron

itrob

enze

ney

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y 2

34

56-

Pen

tach

loro

phen

olt

echn

ical

grad

ez P

enta

nalm

ethy

lfor

myl

hydr

azon

eP

hena

zopy

ridi

neH

Clz

Phe

noba

rbit

aly

Phen

obar

bita

lso

dium

z Ph

enyl

buta

zone

z o-

Phen

ylen

edia

min

e2H

Clz

Pipe

rony

l-bu

toxi

dez

Pipe

rony

lsul

foxi

dey

Poly

brom

inat

edbi

phen

ylm

ixtu

rez

Prob

enec

idy

N-N

-Pro

pyl-

N-f

orm

ylhy

draz

ine

Damp

Cre

dno

5z

Rif

ampi

ciny

Rip

azep

amy

p-R

osan

iline

HC

lz S

afro

lez

Sali

cyla

zosu

lfap

yrid

inez

Sel

eniu

mdi

ethy

ldith

ioca

rbam

ate

Sel

eniu

msu

lde

z S

trob

ane

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

11

12-

Tetr

achl

oroe

than

ey 1

12

2-Te

trac

hlor

oeth

aney

Tetr

achl

oroe

thyl

enez

Tetr

achl

orvi

npho

sy Te

tra

uoro

-m-p

heny

lene

diam

ine

2HC

ly Te

tra

uoro

ethy

lene

z Te

trah

ydro

fura

nz T

hioa

ceta

mid

ez 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

m-T

olui

dine

HC

ly o-

Tolu

idin

eH

Clz

p-To

luid

ine

HC

ly To

xaph

eney

T-2

toxi

nT

riam

tere

ney

Tri

chlo

roac

etic

acid

y 2

46-

Tri

chlo

roan

iline

y 1

12-

Tri

chlo

roet

hane

y T

rich

loro

ethy

lene

z T

rich

loro

ethy

lene

( wit

hout

epic

hlor

ohyd

rin)

y 2

46-

Tri

chlo

roph

enol

z 1

23-

Tri

chlo

ropr

opan

ez T

ri

ural

int

echn

ical

grad

ey 2

45-

Tri

met

hyla

nili

nez

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nilin

eH

Clz

24

6-T

rini

tro-

13-

dim

ethy

l-5-

tert

-but

ylbe

nzen

eT

ris(

2-ch

loro

ethy

l)ph

osph

atez

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez T

ris(

2-et

hylh

exyl

) pho

spha

tey

Trp

-P-1

acet

atez

Trp

-P-2

acet

atez

Ure

than

ez V

inyl

carb

amat

eV

inyl

uo

ride

z 2

5-X

ylid

ine

HC

lz C

Id

ispe

rse

yell

ow3z

Zea

rale

none

y

Mon

key

8A

ato

xin

B1y

Cyc

asin

and

met

hyla

zoxy

met

hano

lace

tate

IQ

z N

-Nitr

osod

ieth

ylam

ine

N-N

itro

sodi

prop

ylam

ine

N-N

itro

sopi

peri

dine

z S

teri

gmat

ocys

tinz

Ure

than

ez

Rat

206

Ace

tam

idez

Ace

tam

inop

henz

Ace

toxi

me

2-A

cety

lam

ino

uore

nez

A

atox

icol

A

atox

inB

y 1A

at

oxin

cru

dez

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

min

o-2-

met

hyla

nthr

aqui

none

z 2-

Am

inoa

nthr

aqui

none

z o-

Am

inoa

zoto

luen

ey 11

-Am

inou

ndec

anoi

cac

idy

Ara

mit

ez A

rocl

or12

60A

uram

ine-

Oz

Azo

xym

etha

neB

emit

radi

ne

Ben

zidi

ne3

-Ben

zyls

ydno

ne-4

-ace

tam

idez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

CI

dir

ectb

lue

15

Bro

mod

ichl

orom

etha

nez

Bud

eson

ide

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Chl

oren

dic

acid

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 2-

Chl

oro-

5-( 3

5-d

imet

hylp

iper

idin

osul

phon

yl) b

enzo

icac

id[

4-C

hlor

o-6-

( 23

-xy

lidi

no) -

2-py

rim

idin

ylth

io] a

ceti

cac

idz

4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

( N-b

-hyd

roxy

ethy

l)ac

etam

idez

Chl

orob

enze

ney

Chl

orof

orm

z 3-

( p-C

hlor

ophe

nyl)

-11

-dim

ethy

lure

ay C

ipro

bra

tez

Cliv

orin

eC

lob

rate

y C

loph

enA

30C

oum

arin

z p-

Cre

sidi

nez

Cro

tona

ldeh

yde

Cup

ferr

onz

Cyc

lope

ntan

one

oxim

eD

DT

z D

ecab

rom

odip

heny

loxi

dey

Deh

ydro

epia

ndro

ster

one

Deh

ydro

epia

ndro

ster

one

acet

ate

24-

Dia

min

otol

uene

z 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ibro

moe

than

ez D

ichl

oroa

ceti

cac

idz

Dic

hlor

oace

tyle

nez

NN

-Die

thyl

-4-(

4-[

pyri

dyl-

1-o

xide

] azo

) ani

line

Die

thyl

stil

best

rolz

Dim

etho

xane

3

3-D

imet

hoxy

benz

idin

e2H

Cl

56-

Dim

etho

xyst

erig

mat

ocys

tinN

N-D

imet

hyl-

4-am

inoa

zobe

nzen

e6-

Dim

ethy

lam

ino-

44-

diph

enyl

-3-h

epta

nola

ceta

teH

Cly

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hyln

itram

ine

Din

itros

ohom

opip

eraz

ine

26-

Din

itro

tolu

ene

24-

Din

itrot

olue

ne( c

onta

inin

g1

0-1

52

6-di

nitr

otol

uene

)z

Din

itrot

olue

net

echn

ical

grad

e( 2

4( 7

7) -

and

26

( 19

) -)

14-

Dio

xane

z D

ipen

tyln

itro

sam

ine

Dox

ylam

ine

succ

inat

ez E

thin

yles

trad

iol

Eth

ioni

ne

dl-E

thio

nine

z 4-

Eth

oxy-

phen

ylur

eaE

thyl

alco

holy

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neE

thyl

ene

thio

urea

z di

( 2-E

thyl

hexy

l)ph

thal

atez

Flu

cona

zole

y N

-(2-

Flu

oren

yl) -

22

2-tr

iuo

roac

etam

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

Fum

onis

inB

1F

uran

z Fu

rfur

alz

Glu

-P-1

z G

lu-P

-2z

FDamp

Cgr

een

no1

y H

CD

Dm

ixtu

rez

Hex

achl

orob

enze

nez

a-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

z H

ydra

zine

z H

ydra

zine

sulf

atez

Hyd

razo

benz

enez

Hyd

roch

loro

uor

ocar

bon

123

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z 1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-nitr

oso-

3-ch

loro

ethy

lure

a1

-Hyd

roxy

safr

olez

IQz

IQH

Cl

Ison

iazi

dz K

epon

ez L

asio

carp

ine

MeA

-a-C

acet

atez

MeI

Qxz

Met

hapy

rile

neH

Cl

Z-M

ethy

l-O

NN

-azo

xyet

hane

Met

hylc

arba

mat

ey M

ethy

lclo

fena

pate

z 3

-Met

hyl-

4-di

met

hyla

min

oazo

benz

ene

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

4-( 4

-N-M

ethy

l-N

-nit

rosa

min

osty

ryl)

quin

olin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line

) 4

4-M

ethy

lene

dian

ilin

e2H

Clz

4-( M

ethy

lnit

rosa

min

o)-1

-(3-

pyri

dyl)

-1-(

buta

none

) M

etro

nida

zole

z M

ichl

errsquos

keto

nez

Mir

exz

Mon

ocro

tali

neN

afen

opin

Nit

rite

sod

ium

y N

itrob

enze

nez

2-N

itro

buta

ne2

-Nit

ro

uore

ne3

-Nit

rope

ntan

eN

-Nitr

oso-

bis-

( 44

4-t

ri

uoro

-N-b

utyl

) am

ine

1-N

itros

o-5

6-di

hydr

oura

cil

N-N

itro

so-2

3-d

ihyd

roxy

prop

ylet

hano

lam

ine

1-N

itros

o-1-

hydr

oxye

thyl

-3-c

hlor

oeth

ylur

ea1

-Nitr

oso-

1-( 2

-hyd

roxy

prop

yl) -

3-ch

loro

ethy

lure

aN

-Nitr

oso-

( 2-h

ydro

xypr

opyl

) -( 2

-hyd

roxy

ethy

l)am

ine

N-N

itros

o-N

-met

hyl-

N-d

odec

ylam

ine

Nit

roso

-N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

e

( Con

tinue

don

next

page

)

643

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

N-N

itro

so-N

-met

hyld

ecyl

amin

e3-

Nit

roso

-2-o

xazo

lidin

one

Nit

roso

-2-o

xopr

opyl

etha

nola

min

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osoa

llyl

etha

nola

min

eN

-Nit

roso

bis(

2-ox

opro

pyl)

amin

eN

itro

sodi

buty

lam

inez

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

imet

hyla

min

ez p-

Nitr

osod

iphe

nyla

min

ez N

-Nit

roso

dipr

opyl

amin

eN

itros

odod

ecam

ethy

lene

imin

eN

-Nit

roso

ephe

drin

eN

itro

soet

hylm

ethy

lam

ine

Nitr

osoh

epta

met

hyle

neim

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

met

hyl-

( 2-h

ydro

xyet

hyl)

amin

eN

-Nitr

osom

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

-Nitr

osom

ethy

l(2-

oxop

ropy

l)am

ine

N-N

itro

som

ethy

l-( 2

-tos

ylox

yeth

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eN

-Nit

roso

mor

phol

ine

N-N

itros

opip

erid

inez

N-N

itro

sopy

rrol

idin

ez N

-Nit

roso

thia

ldin

eo-

Nit

roso

tolu

ene

Nor

lest

rinz

N-(

9-O

xo-2

-uo

reny

l)ac

etam

ide

44

-Oxy

dian

iline

z 2

34

56-

Pent

achl

orop

heno

lte

chni

calg

rade

z P

etas

iten

ine

Phe

noba

rbit

als

odiu

mz

1-P

heny

lazo

-2-n

apht

holy

o-P

heny

lene

diam

ine

2HC

lz P

iper

onyl

buto

xide

z P

olyb

rom

inat

edbi

phen

ylm

ixtu

rez

Pre

dnis

olon

eP

yril

amin

em

alea

tey

CI

aci

dre

d11

4C

Ip

igm

entr

ed3z

Damp

Cre

dno

5z

Damp

Cre

dno

9y

FD

ampC

red

no1

p-

Ros

anili

neH

Clz

Saf

role

z Se

leni

umsu

lde

z Se

nkir

kine

Ste

rigm

atoc

ystin

z S

ymph

ytin

eTa

mox

ifen

citr

atez

Telo

neII

tec

hnic

algr

adez

33

44

-Te

traa

min

obip

heny

l4H

Clz

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

auo

roet

hyle

nez

Thi

oace

tam

idez

44

-Thi

odia

nilin

ez To

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

Tri

amci

nolo

neac

eton

ide

24

5-T

rim

ethy

lani

line

z 2

45-

Tri

met

hyla

nili

neH

Clz

24

6-T

rim

ethy

lani

line

HC

lz T

rini

trog

lyce

rin

Trp

-P-1

acet

atez

Trp

-P-2

acet

atez

Vin

ylac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

CI

dis

pers

eye

llow

3z

Tre

esh

rew

1A

ato

xin

B1y

Lun

gH

amst

er3

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

1-N

itro

so-3

45

-tri

met

hylp

iper

azin

eM

ouse

116

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-is

onic

otin

oylh

ydra

zine

A

llyl

hydr

azin

eH

Cl

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

Are

coli

neH

Cl

5-A

zacy

tidi

nez

Ben

zene

z B

enzo

fura

nz B

enzo

tric

hlor

ide

Ben

zoyl

hydr

azin

eB

enzy

lhyd

razi

ne2

HC

l2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 2-c

hlor

o-1-

met

hyle

thyl

) eth

er

tech

nica

lgra

dey

Bis

-(ch

loro

met

hyl)

ethe

rz 1

3-B

utad

iene

z N

-n-B

utyl

-N-f

orm

ylhy

draz

ine

But

ylat

edhy

drox

ytol

uene

y 1

1-di

-n-B

utyl

hydr

azin

en-

But

ylhy

draz

ine

HC

l1

2-di

-N-B

utyl

hydr

azin

e2H

Cl

Caf

feic

acid

z C

arba

myl

hydr

azin

eH

Cl

1-C

arba

myl

-2-p

heny

lhyd

razi

neC

hlor

ambu

cilz

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z C

oum

arin

z C

yclo

phos

pham

idez

Dac

arba

zine

z D

amin

ozid

ez p

p-D

DD

y D

DT

z 1

1-D

iall

ylhy

draz

ine

12-

Dia

llyl

hydr

azin

e2H

Cl

Dib

enz(

ah)

anth

race

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

Dib

rom

odul

cito

lz 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

12-

Dic

hlor

oeth

anez

12-

Dif

orm

ylhy

draz

ine

Dih

ydro

safr

olez

25-

Dim

etho

xy-4

-am

inos

tilbe

nez

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

a-E

cdys

one

Est

radi

olm

usta

rdy

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylen

eim

ine

Eth

ylen

eox

idez

Eth

ylhy

draz

ine

HC

l5-

Flu

orou

raci

ly Fo

rmyl

hydr

azin

eG

lyci

dolz

c-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

y H

exan

alm

ethy

lfor

myl

hydr

azon

eH

ydra

zine

z H

ydra

zine

sulf

atez

IQz

Isob

utyl

nitr

itez

Ison

iazi

dz Is

onic

otin

icac

idva

nilly

liden

ehyd

razi

de

Isop

rene

Lov

asta

tinM

eIQ

xz M

elph

alan

z 1-

Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m

N-M

ethy

l-N

-for

myl

hydr

azin

eM

ethy

lmet

hane

sulf

onat

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eM

ethy

lene

chlo

ride

z M

ethy

lhyd

razi

ne

Met

hylh

ydra

zine

sulf

ate

( N-6

) -( M

ethy

lnit

roso

) ade

nine

(N

-6) -

( Met

hyln

itro

so) a

deno

sine

N-M

ethy

lola

cryl

amid

ey M

etro

nida

zole

z M

olyb

denu

mtr

ioxi

dey

Mon

oace

tylh

ydra

zine

Nap

htha

lene

15

-Nap

htha

lene

diam

inez

Nic

otin

icac

idhy

draz

ide

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez 3-

Nitr

o-3-

hexe

nez

Nit

robe

nzen

ez N

itrom

etha

nez

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

dim

ethy

lam

inez

N-N

itros

ohex

amet

hyle

neim

ine

N-N

itro

sopi

peri

dine

z O

zone

y Pe

ntan

alm

ethy

lfor

myl

hydr

azon

en-

Pen

tylh

ydra

zine

HC

lPh

enes

teri

nz Ph

enyl

ethy

lhyd

razi

nesu

lfat

eP

roca

rbaz

ine

HC

lz N

-N-P

ropy

l-N

-for

myl

hydr

azin

eP

ropy

lhyd

razi

neH

Cl

Sel

eniu

msu

lde

z S

trep

tozo

toci

nz Su

lfal

late

z Te

lone

IIt

echn

ical

grad

ez 3

34

4-T

etra

amin

obip

heny

l4H

Clz

Tetr

anitr

omet

hane

z T-

2to

xin

Tri

chlo

roet

hyle

nez

Tri

ura

lint

echn

ical

grad

ey 2

45-

Tri

met

hyla

nilin

eH

Clz

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez U

reth

anez

Vin

ylch

lori

dez

Vin

ylu

orid

ez V

inyl

iden

ech

lori

dey

24-

Xyl

idin

eH

Cly

Mon

key

1U

reth

anez

Rat

551-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro

-2-f

uryl

) -1

34-

oxad

iazo

le2

-Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-5-

nitr

othi

azol

ey 1-

Am

yl-1

-nitr

osou

rea

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is-(

chlo

rom

ethy

l)et

herz

HC

blue

no1

z B

rom

oeth

anez

N-n

-But

yl-N

-nit

roso

urea

Cad

miu

mch

lori

deC

adm

ium

sulp

hate

( 11

) 1-

Chl

oroe

thyl

nitr

oso-

3-( 2

-hyd

roxy

prop

yl) u

rea

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z 1

2-D

ibro

moe

than

ez D

imet

hylh

ydro

gen

phos

phit

ey tr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-

[ 2-(

5-ni

tro-

2-fu

ryl)

viny

l] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

12-

Epo

xybu

tane

y 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

Hyd

razi

nez

Hyd

razi

nesu

lfat

ez 1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

Isob

utyl

nitr

itez

Ison

iazi

dz 4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4-

( Met

hyln

itros

amin

o)-1

-(3-

pyri

dyl)

-1-b

utan

ol4

-(M

ethy

lnit

rosa

min

o)-1

-(3-

pyri

dyl)

-1-(

buta

none

) N

-[ 3

-(5-

Nitr

o-2-

fury

l)-

12

4-ox

adia

zole

-5-y

l] -m

ethy

lace

tam

ide

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

3-N

itro-

3-he

xene

z 5-

Nitr

oace

naph

then

ez N

-Nit

roso

-bis

-(4

44-

tri

uoro

-N-b

utyl

) am

ine

N-N

itros

o-N

-met

hyl-

N-d

odec

ylam

ine

N-N

itros

o-N

-met

hyl-

N-t

etra

decy

lam

ine

N-N

itro

so-N

-met

hyld

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

lure

az N

-Nitr

osob

is( 2

-hyd

roxy

prop

yl)

amin

eN

-Nitr

osob

is-2

3-d

ihyd

roxy

prop

ylam

ine

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itros

odim

ethy

lam

inez

N-N

itro

soep

hedr

ine

Nitr

osoe

thyl

met

hyla

min

eN

-Nit

roso

met

hyl

N-N

itro

som

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eC

Ia

cid

red

114

Sod

ium

dich

rom

ate

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

anit

rom

etha

nez

24

5-T

rim

ethy

lani

line

z 2

46-

Tri

met

hyla

nili

neH

Clz

Vin

ylch

lori

dez

Mam

mar

ygl

and

Dog

1Ly

nest

reno

lH

amst

er1

Vin

ylch

lori

dez

Mou

se24

5-A

zacy

tidin

ez B

enze

nez

CI

dir

ectb

lack

381

3-B

utad

iene

z C

alci

fero

lC

hlor

opre

nez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Die

thyl

stilb

estr

olz

a-E

cdys

one

Est

radi

olE

thyl

ene

oxid

ez F

uros

emid

ey G

lyci

dolz

Gri

seof

ulvi

nIs

onia

zidz

Ison

icot

inic

acid

vani

llylid

eneh

ydra

zide

( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Nitr

oben

zene

z R

eser

pine

z Su

lfal

late

z V

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y

644

Rat

102

4-A

cety

lam

inob

iphe

nyl

2-A

cety

lam

ino

uore

nez

Acr

onyc

ine

Acr

ylam

ide

Acr

ylon

itri

leA

F-2

z 1-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro-

2-fu

ryl)

-13

4-

oxad

iazo

le2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

e2-

Am

ino-

5-ni

trot

hiaz

oley

4-A

min

odip

heny

lHC

l1-

Am

yl-1

-nit

roso

urea

Atr

azin

ey B

emit

radi

ne

Ben

zidi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

4-B

is( 2

-hyd

roxy

ethy

l)am

ino-

2-( 5

-nit

ro-2

-thi

enyl

) qui

nazo

line

13-

But

adie

nez

N-n

-But

yl-N

-nitr

osou

rea

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Car

boxy

met

hyln

itros

oure

aC

hlor

ambu

cilz

Chl

orop

rene

z C

ytem

bena

y D

acar

bazi

nez

N-1

-Dia

ceta

mid

ouo

rene

46

-Dia

min

o-2-

( 5-n

itro-

2-fu

ryl)

-S-t

riaz

ine

24-

Dia

min

oani

sole

sulf

atez

24-

Dia

min

otol

uene

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dib

rom

oman

nito

lz 1

3-D

ibut

yl-1

-nit

roso

urea

33

-Dic

hlor

oben

zidi

ne1

2-D

ichl

oroe

than

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

12-

Dim

ethy

l-5-

nitr

oim

idaz

ole

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lam

inoe

thyl

nitr

osoe

thyl

urea

nitr

ite

salt

33

-Dim

ethy

lben

zidi

ne2

HC

lz 2-

( 22

-Dim

ethy

lhyd

razi

no) -

4-( 5

-nitr

o-2-

fury

l)th

iazo

le

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

24-

Dio

xane

z 1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

6-di

nitr

otol

uene

)zN

-(2-

Fluo

reny

l)-2

22

-tri

uo

roac

etam

ide

Form

icac

id2-

( 4-m

ethy

l-2-

thia

zoly

l)hy

draz

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-

thia

zoly

l] hyd

razi

dez

Gly

cido

lz H

exam

ethy

lmel

amin

eN

-Hex

ylni

tros

oure

a2-

Hyd

razi

no-4

-(p-

amin

ophe

nyl)

thia

zole

z 2-

Hyd

razi

no-4

-( 5

-nit

ro-2

-fur

yl) t

hiaz

olez

2-H

ydra

zino

-4-(

p-ni

trop

heny

l)th

iazo

lez

Hyd

razo

benz

enez

1-( 2

-Hyd

roxy

ethy

l)-3

-[( 5

-nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

e1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

1-(

2-H

ydro

xyet

hyl)

-1-n

itros

oure

az In

dom

etha

cin

IQz

IQH

Cl

Ison

iazi

dz 2-

Met

hoxy

-3-a

min

odib

enzo

fura

n4-

Met

hyl-

1-[(

5-ni

trof

urfu

rylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

-(N

-Met

hyl-

N-n

itro

soca

rbam

oyl)

-l-o

rnit

hine

3-M

ethy

lcho

lant

hren

e4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line)

Met

hyle

nech

lori

dez

Met

roni

dazo

lez

l-5-

Mor

phol

inom

ethy

l-3-

[(5-

nitr

ofur

fury

lide

ne) a

min

o]-

2-ox

azol

idin

one

HC

lN

ithia

zide

z 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

3-( 5

-Nitr

o-2-

fury

l)-i

mid

azo(

12-

a)

pyri

dine

z 4-

( 5-N

itro-

2-fu

ryl)

thia

zole

N

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

ide

NN

-[6-

( 5-N

itro

-2-f

uryl

) -S-

tria

zine

-24

-diy

l] bis

acet

amid

e5-

Nitr

oace

naph

then

ez 1-

[(5-

Nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

itrom

etha

nez

1-N

itrop

yren

eN

orle

stri

nz O

chra

toxi

nA

z N

-(9-

Oxo

-2-

uore

nyl)

acet

amid

ePh

enac

etin

z Ph

enes

teri

nz Ph

IPH

Clz

Proc

arba

zine

HC

lz Pr

opan

esu

lton

e1

2-Pr

opyl

ene

oxid

ez St

yren

ey Su

lfal

late

z 4

4-S

ulfo

nylb

isac

etan

ilid

eTo

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uor

o-N

-[4-

( 5-n

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

idez

Trp

-P-2

acet

atez

Vin

ylch

lori

dez

FD

ampC

viol

etno

1y

Mes

ovar

ium

Rat

2Sa

lbut

amol

Ter

buta

line

Myo

card

ium

Mou

se2

Est

radi

olm

usta

rdy

Phen

este

rinz

Nas

alca

vity

bB

ush

baby

1N

-Nitr

osod

ieth

ylam

ine

Ham

ster

11A

ceta

ldeh

yde

Dia

llyln

itros

amin

eD

imet

hylc

arba

myl

chlo

ride

Hyd

razi

nez

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osom

ethy

l-2

3-di

hydr

oxyp

ropy

lam

ine

N-N

itros

omor

phol

ine

N-N

itros

onor

nico

tine

N-N

itros

opip

erid

inez

Mou

se6

Ally

lgly

cidy

leth

ery

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 1

2-D

ibro

moe

than

ez Fo

rmal

dehy

dez

N-N

itro

sohe

xam

ethy

lene

imin

e1

2-Pr

opyl

ene

oxid

ez

Rat

43A

ceta

ldeh

yde

Acr

ylon

itril

e1-

Azo

xypr

opan

eB

enze

nez

Bis

-(ch

loro

met

hyl)

ethe

rz p-

Cre

sidi

nez

Dia

llyln

itros

amin

e1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dim

ethy

lnitr

amin

eD

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

e1

4-D

ioxa

nez

12-

Epo

xybu

tane

y Z

-Eth

yl-O

NN

-azo

xyet

hane

E

thyl

benz

ene

Eth

ylni

tros

ocya

nam

ide

Form

alde

hyde

z H

exam

ethy

lpho

spho

ram

ide

Hyd

razi

nez

N-N

itro

so-N

-met

hyld

ecyl

amin

edi

( N-N

itro

so) -

perh

ydro

pyri

mid

ine

N-N

itros

o(2

22-

tri

uoro

ethy

l)et

hyla

min

e1-

Nitr

oso-

34

5-tr

imet

hylp

iper

azin

eN

-Nitr

osoa

llyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyle

than

olam

ine

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

dipr

opyl

amin

eN

itros

oeth

ylm

ethy

lam

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nitr

osom

ethy

l-( 2

-hyd

roxy

ethy

l)am

ine

N-N

itro

som

ethy

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

norn

icot

ine-

1-N

-oxi

de

N-N

itro

sopi

peri

dine

z P

hena

cetin

z Ph

enyl

glyc

idyl

ethe

r1

2-Pr

opyl

ene

oxid

ez V

inyl

acet

atez

Vin

ylch

lori

dez

Ner

vous

Mou

se3

13-

But

adie

nez

N-N

itros

odim

ethy

lam

inez

Pro

carb

azin

eH

Clz

syst

emR

at21

Acr

ylam

ide

Acr

ylon

itril

eB

rom

oeth

anez

Chl

oram

buci

lz 1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

eC

yclo

phos

pham

idez

1-E

thyl

-1-n

itros

oure

aE

thyl

eneo

xide

z 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

eaG

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

R(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

S(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

M

ethy

lnit

ram

ine

N-N

itros

o-N

-met

hylu

reaz

N-N

itros

odie

than

olam

ine

1-P

heny

l-3

3-di

met

hyltr

iaze

neP

roca

rbaz

ine

HC

lz P

ropa

nesu

ltone

Vin

ylch

lori

dez

Ora

lcav

ityc

Ham

ster

4A

ceta

ldeh

yde

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itros

omor

phol

ine

N-N

itro

sopi

peri

dine

z

Mou

se3

N-N

itros

ohex

amet

hyle

neim

ine

12

3-T

rich

loro

prop

anez

Vin

ylac

etat

ez

Rat

32A

cryl

amid

eA

cryl

onitr

ile

Ben

zene

z 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

CI

dir

ectb

lue

15C

Id

irec

tblu

e21

8z C

hlor

opre

nez

3-D

iazo

tyra

min

eH

Cl

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

eG

lyci

dolz

IQz

MeA

-a-C

acet

atez

N-N

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

hydr

oxyp

ropy

lam

ine

Nit

roso

-23

-dih

ydro

xypr

opyl

-2-

oxop

ropy

lam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

itro

soam

ylur

etha

nN

-Nitr

osod

ieth

ylam

ine

Nit

roso

ethy

lure

than

N

itros

ohep

tam

ethy

lene

imin

e1-

Nitr

osoh

ydan

toin

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

thia

ldin

eN

-Nitr

osot

hiom

orph

olin

eC

Ia

cid

red

114

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tolu

eney

12

3-T

rich

loro

prop

anez

Xyl

ene

mix

ture

( m-x

ylen

eo-

xyle

nep

-xyl

ene)

Ova

ryM

ouse

10B

enze

nez

13-

But

adie

nez

Die

thyl

stil

best

rolz

N-M

ethy

lola

cryl

amid

ey 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

5-N

itroa

cena

phth

enez

1-[(

5-N

itro

furf

uryl

iden

e)am

ino]

hyda

ntoi

nz P

heno

lpht

hale

inz

Tam

oxif

enci

trat

ez 4-

Vin

ylcy

cloh

exen

ePa

ncre

asH

amst

er3

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

itro

so-2

6-d

imet

hylm

orph

olin

eN

itro

so-2

-oxo

prop

ylet

hano

lam

ine

Mon

key

1U

reth

anez

Rat

222-

Am

ino-

5-ni

trop

heno

ly 1-

( Am

inom

ethy

l)cy

cloh

exan

eace

ticac

idA

zase

rine

But

ylbe

nzyl

phth

alat

ey C

hlor

endi

cac

idz

Cin

nam

ylan

thra

nila

tez

Clo

bra

tey

Dic

hlor

vosz

Eth

ylal

coho

ly H

ydro

chlo

ro

uoro

carb

on12

3IQ

HC

lM

alon

alde

hyde

sod

ium

saltz

MeA

-a-C

acet

atez

2-M

erca

ptob

enzo

thia

zole

y M

ethy

lclo

fena

pate

z N

-(N

-Met

hyl-

N-n

itros

ocar

bam

oyl)

-l-o

rnit

hine

4-(

Met

hyln

itro

sam

ino)

-1-(

3-py

ridy

l)-1

-but

anol

4-(

Met

hyln

itros

amin

o)-1

-( 3

-pyr

idyl

) -1-

( but

anon

e)N

afen

opin

Nitr

ofen

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)z1

23

-Tri

chlo

ropr

opan

ez

Peri

tone

alM

ouse

8B

is-1

2-(

chlo

rom

etho

xy) e

than

eB

is-1

4-(

chlo

rom

etho

xy) -

p-xy

lene

Bis

-(ch

loro

met

hyl)

ethe

rz C

hlor

opre

nez

tran

s-1

4-D

ichl

orob

uten

e-2

cavi

tyD

imet

hylc

arba

myl

chlo

ride

Phe

noxy

benz

amin

eH

Clz

Tri

s-1

23-

( chl

orom

etho

xy) p

ropa

neR

at22

Acr

onyc

ine

Acr

ylam

ide

Act

inom

ycin

DA

nili

neH

Cly

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

rom

ate

pota

ssiu

mz

Chl

oroz

otoc

in

Cyt

embe

nay

Dap

sone

y 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

4-D

ioxa

nez

Eth

ylen

eox

idez

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz M

elph

alan

z N

-Met

hyl-

N4

-din

itros

oani

line

Mit

omyc

in-C

N-N

itro

so-2

24

-tri

met

hyl-

12-

dihy

droq

uino

line

poly

mer

Ph

enox

yben

zam

ine

HC

lz o-

Tolu

idin

eH

Clz

( Con

tinue

don

next

page

)

645

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Pitu

itar

ygl

and

Mou

se8

Die

thyl

stil

best

rolz

Eno

vid

Eth

ylen

eth

iour

eaz

Iodi

nate

dgl

ycer

olz

Isop

rene

Nor

lest

rinz

Pro

pylt

hiou

raci

lz Z

eara

leno

ney

Rat

73-

Am

inot

riaz

olez

12-

Dib

rom

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylal

coho

ly 2-

Mer

capt

oben

zoth

iazo

ley

Met

roni

dazo

lez

Nor

lest

rinz

Pros

tate

Rat

4C

adm

ium

chlo

ride

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

PhIP

HC

lz

Skin

Ham

ster

2U

reth

anez

Vin

ylch

lori

dez

Mou

se5

5-A

zacy

tidin

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Chl

orop

rene

z G

lyci

dolz

Thi

o-te

paz

Rat

332-

Ace

tyla

min

ouo

rene

z 3-

Am

ino-

9-et

hylc

arba

zole

mix

ture

z 1-

Azo

xypr

opan

e2-

Azo

xypr

opan

eB

enze

nez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

ol

tech

nica

lgra

dez

CI

dir

ectb

lue

15C

arbo

xym

ethy

lnitr

osou

rea

24-

Dia

min

oani

sole

sulf

atez

Dib

rom

odul

cito

lz D

ibro

mom

anni

tolz

Dim

etho

xane

2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

Dim

ethy

lvin

ylch

lori

dez

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

26-

dini

trot

olue

ne)z

1-E

thyl

nitr

oso-

3-( 2

-hyd

roxy

ethy

l)-u

rea

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz 1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

IQ

z L

asio

carp

ine

MeI

Qxz

N-(

N-M

ethy

l-N

-nitr

osoc

arba

moy

l)-l

-orn

ithi

ne

5-N

itro-

o-an

isid

inez

CI

aci

dre

d11

4p-

Ros

anili

neH

Clz

Thi

o-te

paz

Thi

oure

ay V

inyl

chlo

ride

z F

Damp

Cvi

olet

no1

y

Smal

lint

esti

neM

ouse

6C

apta

folz

Cap

tanz

N-E

thyl

-N-n

itro

-N-n

itro

sogu

anid

ine

Hyd

roge

npe

roxi

deN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-(

Tri

chlo

rom

ethy

lthi

o)ph

thal

imid

eM

onke

y1

Ure

than

ez

Rat

29A

cryl

onitr

ile

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is( 2

3-d

ibro

mop

ropy

l)ph

osph

ate

mag

nesi

umsa

lt4

-Bis

( 2-h

ydro

xyet

hyl)

amin

o-2-

( 5-n

itro

-2-t

hien

yl) q

uina

zolin

eC

Id

irec

tblu

e15

Car

boxy

met

hyln

itros

oure

a1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

e2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro

-2-f

uryl

)py

rim

idin

etr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-[

2-( 5

-nit

ro-2

-fur

yl) v

inyl

] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

Z-E

thyl

-ON

N-a

zoxy

met

hane

1-E

thyl

-1-n

itros

oure

aFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lu-P

-1z

Glu

-P-2

z IQ

z L

asio

carp

ine

N-M

ethy

l-N

-nitr

o-N

-nitr

osog

uani

dine

z N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez N

-Nitr

oso-

N-i

sobu

tylu

rea

3-N

itro

so-2

-oxa

zoli

dino

neN

itro

soet

hylu

reth

ane

PhI

PH

Clz

Pro

pane

sulto

neQ

uerc

etin

y C

Ia

cid

red

114

Trp

-P-2

acet

atez

Sple

enR

at7

Ani

line

HC

ly A

zobe

nzen

ey p-

Chl

oroa

nili

neH

Clz

Dap

sone

y o-

Nitr

osot

olue

neD

ampC

red

no9

y o-

Tolu

idin

eH

Clz

Stom

ach

Ham

ster

18A

F-2z

14-

Din

itros

o-2

6-di

met

hylp

iper

azin

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z H

ydra

zine

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] a

ceta

mid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

N-N

itro

so-2

3-d

ihyd

roxy

prop

yl-2

-hyd

roxy

prop

ylam

ine

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

-Nitr

oso-

ethy

l-2-

oxop

ropy

lure

aN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

itros

o-5-

met

hylo

xazo

lidon

eN

-Nit

roso

-N-m

ethy

lure

than

N-N

itros

o-1

3-ox

azol

idin

eN

-Nit

roso

-2-p

heny

leth

ylur

ea1

-Nit

roso

-34

5-t

rim

ethy

lpip

eraz

ine

Ure

than

ez V

inyl

chlo

ride

z

Mou

se63

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eA

ciu

orfe

nA

F-2

z 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

tran

s-5-

Am

ino-

3[2-

( 5-n

itro-

2-fu

ryl)

viny

l] -1

24-

oxad

iazo

leA

reco

line

HC

lB

enza

ldeh

ydey

Ben

zofu

ranz

Ben

zotr

ichl

orid

eB

enzy

lace

tate

y B

enzy

lchl

orid

ey B

rom

oeth

anol

13

-But

adie

nez

But

ylat

edhy

drox

yani

sole

z 1

1-di

-N-B

utyl

hydr

azin

eC

affe

icac

idz

Cap

tafo

lz C

arba

zole

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z3

-(C

hlor

omet

hyl)

pyri

dine

HC

lz C

hlor

opre

nez

2-C

hlor

opro

pana

l1-

Chl

orop

rope

neC

ypro

tero

neac

etat

e1

1-D

ially

lhyd

razi

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dic

hlor

vosz

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez D

imet

hylv

inyl

chlo

ride

z D

init

roso

pipe

razi

neE

stra

diol

mus

tard

y E

thyl

acry

late

z Fo

rmic

acid

2-[ 4

-( 5

-nit

ro-2

-fur

yl) -

2-th

iazo

lyl] h

ydra

zide

z G

lyci

dolz

2-H

ydra

zino

-4-(

5-ni

tro-

2-fu

ryl)

thia

zole

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

ICI

1628

46z

IQz

Isop

rene

Lov

asta

tin

MeI

Q1

-Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m3

-(5-

Nitr

o-2-

fury

l)-

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] f

orm

amid

ez N

-Nit

roso

-N

-met

hylu

reaz

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

hexa

met

hyle

neim

ine

N-N

itros

opip

erid

inez

b-P

ropi

olac

tone

z Se

sam

olz

Sty

rene

oxid

ez Te

lone

IIt

echn

ical

grad

ez N

-(T

rich

loro

met

hylth

io) p

htha

limid

e1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uo

ro-N

-[4-

( 5-n

itro

-2-f

uryl

) -2-

thia

zoly

l]ac

etam

idez

Tri

ur

alin

tec

hnic

algr

adey

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylac

etat

ez

Rat

85A

ceto

ne[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zone

1-A

ceto

xysa

frol

ey A

cryl

onitr

ile

1-A

llyl

-1-n

itro

sour

ea2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-ox

adia

zole

2-

Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-4-

( 5-n

itro

-2-f

uryl

) thi

azol

ez 1-

Am

yl-1

-nit

roso

urea

Ari

stol

ochi

cac

id

sodi

umsa

lt( 7

7A

AI

21

AA

II)

Ben

zene

z B

enzo

( a) p

yren

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

BL

-634

1H

Cl

N-n

-But

yl-N

-nitr

osou

rea

But

ylat

edhy

drox

yani

sole

z b

-But

yrol

acto

neC

affe

icac

idz

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z4

-Chl

oro-

o-ph

enyl

ened

iam

inez

Chl

oro

uoro

met

hane

3-

( Chl

orom

ethy

l)py

ridi

neH

Clz

Cip

rob

rate

z C

upfe

rron

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez 2

5-D

imet

hoxy

-4-a

min

osti

lben

ez D

imet

hylh

ydro

gen

phos

phit

ey 4

6-D

imet

hyl-

2-( 5

-nit

ro-2

-fu

ryl)

pyri

mid

ine

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lvin

ylch

lori

dez

Epi

chlo

rohy

drin

y E

thyl

acry

late

z E

thyl

ene

oxid

ez 2-

Flu

oroe

thyl

-nitr

osou

rea

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-

nitr

osou

reaz

1-( 3

-Hyd

roxy

prop

yl) -

1-ni

tros

oure

a1

-Hyd

roxy

safr

olez

ICI

1628

46z

Lox

tidin

eL

upit

idin

e3H

Cl

Mer

curi

cch

lori

dey

3-M

etho

xyca

tech

ol4

-Met

hoxy

phen

olN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-M

ethy

l-N

-nit

roso

benz

amid

e4-

Met

hylc

atec

hol

Met

hyln

itro

socy

anam

ide

3-( 5

-Nit

ro-2

-fur

yl) -

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

4-( 5

-Nit

ro-2

-fur

yl) t

hiaz

ole

2-N

itro

uo

rene

8-N

itro

quin

olin

eN

itro

so-B

aygo

nN

-Nit

roso

-23

-dih

ydro

xypr

opyl

-2-h

ydro

xypr

opyl

amin

eN

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

oxop

ropy

lam

ine

1-N

itro

so-3

5-d

imet

hyl-

4-be

nzoy

lpip

eraz

ine

N-N

itro

so-N

-met

hyl-

N-d

odec

ylam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itro

so-N

-met

hylu

reaz

Nit

roso

-12

36

-tet

rahy

drop

yrid

ine

N-N

itro

sobe

nzth

iazu

ron

Nitr

osod

ibut

ylam

inez

N-N

itros

odie

thyl

amin

eN

-Nit

roso

ephe

drin

eN

itros

oeth

ylur

etha

nO

mep

razo

ley

Phen

acet

inz

Piv

alol

acto

ney

b-P

ropi

olac

tone

z N

-Pro

pyl-

N-n

itro

-N-n

itro

sogu

anid

ine

12-

Pro

pyle

neox

idez

Ses

amol

z St

yren

eox

idez

Sulf

alla

tez

Telo

neII

tec

hnic

algr

adez

12

3-T

rich

loro

prop

anez

24

6-T

rim

ethy

lani

line

HC

lz

646

Subc

utan

eous

Mou

se4

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

2-D

ibro

moe

than

ez N

2-c

-Glu

tam

yl-p

-hyd

razi

nobe

nzoi

cac

idG

lyci

dolz

tissu

eR

at13

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ichl

oroe

than

ez D

imet

hoxa

ne1

4-D

ioxa

nez

MeA

-a-C

acet

atez

44

-Met

hyle

ne-b

is( 2

-met

hyla

nili

ne)

o-N

itro

soto

luen

ep-

Ros

anili

neH

Clz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 2

45-

Tri

met

hyla

nilin

eH

Clz

25-

Xyl

idin

eH

Clz

Test

isM

ouse

4D

ieth

ylst

ilbe

stro

lz Fi

nast

erid

eR

eser

pine

z Ta

mox

ifen

citr

atez

Rat

185-

Aza

cytid

inez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

3-B

utad

iene

z N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

Cad

miu

mch

lori

de

2-C

hlor

o-1

11-

tri

uoro

etha

ne1

1-D

ichl

oro-

1-u

oroe

than

eH

ydro

chlo

rou

oroc

arbo

n12

3M

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z M

etro

nida

zole

z N

-Nit

roso

dim

ethy

lam

inez

Oxo

linic

acid

y SD

Z20

0-11

01

11

2-Te

tra

uoro

etha

ney

Tri

chlo

roet

hyle

nez

Tri

nitr

ogly

ceri

nV

inyl

chlo

ride

z

Thy

roid

glan

dH

amst

er4

Hex

achl

orob

enze

nez

Hyd

razi

nez

Met

hylt

hiou

raci

lU

reth

anez

Mou

se18

3-A

min

o-4-

etho

xyac

etan

ilide

y H

Cbl

ueno

1z

tert

-But

ylal

coho

lz C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

24

-Dia

min

oani

sole

sulf

atez

Die

thyl

stil

best

rolz

Dox

ylam

ine

succ

inat

ez E

thio

nam

idey

Eth

ylen

eth

iour

eaz

44

-Met

hyle

nedi

anil

ine

2HC

lz 1

5-N

apht

hale

nedi

amin

ez N

itrob

enze

nez

Oxa

zepa

my

44

-Oxy

dian

iline

z C

Ip

igm

entr

ed3z

Sulf

amet

hazi

ne2

37

8-T

etra

chlo

rodi

benz

o-p-

diox

inz

44

-Thi

odia

nilin

ez

Rat

33A

cryl

amid

e3-

Am

inot

riaz

olez

o-A

nisi

dine

HC

lz B

emit

radi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

Chl

orop

rene

z 2

4-D

iam

inoa

niso

lesu

lfat

ez N

N-D

ieth

ylth

iour

eay

1-E

thyl

-1-n

itro

sour

ea

Eth

ylen

eth

iour

eaz

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Flu

vast

atin

Gly

cido

lz Io

dina

ted

glyc

erol

z Is

obut

eney

Mal

onal

dehy

des

odiu

msa

ltz

Met

him

azol

e4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Mir

exp

hoto

-N

itro

benz

enez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

44

-Oxy

dian

iline

z Pr

opyl

thio

urac

ilz p-

Ros

anil

ine

HC

lz 2

37

8-Te

trac

hlor

odib

enzo

-p-d

ioxi

nz 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tri

met

hylt

hiou

reay

Vin

ylac

etat

ez Z

inc

dim

ethy

ldith

ioca

rbam

atez

Uri

nary

blad

der

Dog

23

3-D

ichl

orob

enzi

dine

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nilin

e)H

amst

er3

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

acet

amid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

Mou

se12

2-A

cety

lam

ino

uore

nez

4-A

min

odip

heny

l2-

Am

inod

iphe

nyle

neox

ide

o-A

nisi

dine

HC

lz 4-

Chl

oro-

4-a

min

odip

heny

leth

erz

p-C

resi

dine

z 4-

Eth

ylsu

lpho

nyln

apht

hale

ne-1

-sul

fona

mid

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hena

cetin

z Te

lone

IIt

echn

ical

grad

ez U

raci

lz

Mon

key

12-

Nap

hthy

lam

inez

Rat

49A

ceta

min

ophe

nz A

llyli

soth

iocy

anat

ey 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

4-A

min

o-2-

nitr

ophe

noly

11-A

min

ound

ecan

oic

acid

y o-

Ani

sidi

neH

Clz

Ari

stol

ochi

cac

ids

odiu

msa

lt( 7

7A

AI

21

AA

II)

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

ispe

rse

blue

1y N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

4-C

hlor

o-o-

phen

ylen

edia

min

ez m

-Cre

sidi

ney

p-C

resi

dine

z C

yclo

phos

pham

idez

Die

thyl

ene

glyc

olD

imet

hyla

rsin

icac

idy

Fose

tylA

lIQ

HC

lM

eA-a

-Cac

etat

ez M

elam

iney

2-M

etho

xy-3

-am

inod

iben

zofu

ran

2-N

apht

hyla

min

ez N

itril

otri

acet

icac

idz

Nitr

ilot

riac

etic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez o-

Nitr

oani

sole

z N

-Nitr

oso-

N-m

ethy

l-N

-dod

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

l-N

-tet

rade

cyla

min

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itro

sodi

phen

ylam

iney

o-N

itros

otol

uene

N-O

xydi

ethy

lene

thio

carb

amyl

-N-o

xydi

ethy

lene

sulf

enam

ide

Phe

nace

tinz

Phen

azon

eo-

Phen

ylph

enat

eso

dium

y o-

Phen

ylph

enol

y P

otas

sium

bica

rbon

ate

Purp

urin

Que

rcet

iny

p-Q

uino

nedi

oxim

ey Sa

ccha

rin

sodi

umy

Sali

cyla

zosu

lfap

yrid

inez

o-To

luen

esul

fona

mid

eo-

Tolu

idin

eH

Clz

Trp

-P-2

acet

atez

Ura

cilz

Ute

rus

Ham

ster

1N

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aM

ouse

12B

rom

oeth

anez

Chl

oroe

than

ey D

acar

bazi

nez

12-

Dic

hlor

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylen

eox

idez

Gly

cido

lz ( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Proc

arba

zine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez T

rim

ethy

lpho

spha

tey

Vin

ylac

etat

ez

Rat

26A

cryl

amid

e1-

Ally

l-1-

nitr

osou

rea

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

myl

-1-n

itros

oure

aA

traz

iney

CI

dir

ectb

lue

15B

rom

ocri

ptin

em

esyl

atey

N-n

-But

yl-N

-nit

roso

urea

Cal

cium

valp

roat

eC

apta

nz 2-

Chl

oro-

11

1-tr

iuo

roet

hane

Dac

arba

zine

z D

amin

ozid

ez 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

lD

imet

hyla

min

oeth

ylni

tros

oeth

ylur

ean

itri

tesa

lt1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

ICR

F-1

59z

Isop

hosp

ham

idez

15-

Nap

htha

lene

diam

inez

Nit

robe

nzen

ez N

orle

stri

nz 4

4-T

hiod

iani

linez

Vin

ylac

etat

ez

Vag

ina

Mou

se1

AZ

Tz

Rat

2A

ZT

z N

-n-B

utyl

-N-n

itro

sour

ea( C

ontin

ued

onne

xtpa

ge)

647

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Vas

cula

rsy

stem

Ham

ster

91

2-D

imet

hylh

ydra

zine

2H

Cl

Gly

cido

lz H

exac

hlor

oben

zene

z N

-Nit

roso

-eth

yl-2

-oxo

prop

ylur

eaN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

-Nitr

oso-

oxop

ropy

lchl

oroe

thyl

urea

N-N

itro

so-o

xopr

opyl

urea

N-N

itros

o-2-

phen

ylet

hylu

rea

Vin

ylch

lori

dez

Mou

se59

A-a

-CN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-ph

enyl

hydr

azin

eA

llyl

hydr

azin

eH

Cl

Are

colin

eH

Cl

Aza

thio

prin

eB

enzi

dine

2H

Cl

2-B

iphe

nyla

min

eH

Cly

13-

But

adie

nez

Cap

tafo

lz C

arba

myl

hydr

azin

eH

Cl

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 1-

Chl

oro-

4-ni

trob

enze

ney

5-C

hlor

o-o-

tolu

idin

ey 4-

Chl

oro-

o-to

luid

ine

HC

ly p-

Chl

oroa

nilin

eH

Clz

Chl

orop

rene

z C

upfe

rron

z D

acar

bazi

nez

Dam

inoz

idez

24-

Dia

min

otol

uene

2H

Clz

12-

Dib

rom

oeth

anez

Dif

talo

ne7

12-

Dim

ethy

lben

z(a)

anth

race

ne1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylhy

draz

ine

HC

lG

lu-P

-1z

Glu

-P-2

z p-

Hyd

razi

nobe

nzoi

cac

idH

Cl

1-H

ydro

xysa

frol

ez Is

opre

neM

eA-a

-Cac

etat

ez N

-Met

hyl-

N-f

orm

ylhy

draz

ine

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

Mic

hler

rsquoske

tone

z 5-

Nitr

o-o-

tolu

idin

ey N

itro

fenz

N-N

itros

o-N

-met

hylu

reaz

Pent

achl

oroa

niso

lez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y2

34

56

-Pen

tach

loro

phen

olt

echn

ical

grad

ez n-

Pen

tylh

ydra

zine

HC

lPh

enyl

ethy

lhyd

razi

nesu

lfat

ePh

enyl

hydr

azin

eH

Cl

Ster

igm

atoc

ysti

nz Te

tra

uoro

ethy

lene

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)zo

-Tol

uidi

neH

Clz

24

6-T

rich

loro

anil

iney

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nili

neH

Clz

Ure

than

ez V

inyl

carb

amat

eV

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y 2

5-X

ylid

ine

HC

lz

Mon

key

2A

ato

xin

B1y

Ure

than

ez

Rat

32A

nilin

eH

Cly

Azo

benz

eney

Ben

zene

z C

livor

ine

Cup

ferr

onz

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neI

QH

Cl

Las

ioca

rpin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line)

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-N

itros

o-( 2

-hyd

roxy

prop

yl) -

( 2-h

ydro

xyet

hyl)

amin

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nitr

osob

is( 2

-oxo

prop

yl) a

min

eN

-Nit

roso

diet

hano

lam

ine

N-N

itro

sodi

ethy

lam

ine

N-N

itros

odim

ethy

lam

inez

N-N

itros

omet

hyl-

( 2-t

osyl

oxye

thyl

) am

ine

N-N

itros

omor

phol

ine

N-N

itro

sopy

rrol

idin

ez Pe

tasi

teni

neS

teri

gmat

ocys

tinz

Sym

phyt

ine

Tetr

auo

roet

hyle

nez

o-To

luid

ine

HC

lz T

rp-P

-2ac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

aT

here

was

nore

port

edta

rget

site

in1

spec

ies

( rat

sor

mic

e)fo

r5

chem

ical

sw

ithsu

pers

crip

tsb

utth

ech

emic

alw

asev

alua

ted

byth

epu

blis

hed

auth

oras

aca

rcin

ogen

ald

rinz

diel

drin

z N

-nit

roso

pyrr

olid

inez

23

45

6-pe

ntac

hlor

ophe

nol

( Dow

icid

eE

C-7

)ya

ndur

etha

nez

bN

asal

cavi

tyin

clud

estis

sues

ofth

eno

sen

asal

turb

inat

esp

aran

asal

sinu

ses

and

trac

hea

c Ora

lcav

ityin

clud

estis

sues

ofth

em

outh

oro

phar

ynx

phar

ynx

and

lary

nx

Ach

emic

alis

liste

dun

der

each

orga

nev

alua

ted

aspo

sitiv

ein

anex

peri

men

tin

that

spec

ies

byat

leas

t1au

thor

The

refo

rea

chem

ical

may

beli

sted

unde

rse

vera

ltar

geto

rgan

san

dev

ery

chem

ical

liste

din

the

tabl

eis

posi

tive

inat

leas

t1sp

ecie

sIn

orde

rto

com

pare

resu

ltsin

rats

and

mic

esy

mbo

lsfo

llow

chem

ical

ste

sted

inbo

thsp

ecie

sa

zin

dica

tes

that

the

chem

ical

ispo

sitiv

eat

som

esi

tein

both

spec

ies

and

ay

indi

cate

sth

atit

was

test

edin

both

butp

ositi

vein

only

1a

Nth

enu

mbe

rof

chem

ical

sw

ithat

leas

t1po

sitiv

ete

stat

that

site

inth

atsp

ecie

sB

ecau

sem

any

chem

ical

sin

duce

tum

ors

atm

ore

than

1si

tein

agi

ven

spec

ies

man

ych

emic

als

appe

arm

ore

than

once

inth

eta

ble

648

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649

species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters

RESULTS IN RATS AND MICE

For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens

TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database

Chemicals evaluated as carcinogenic in

Rats Mice

All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)

Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2

a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not

b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats

All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical

to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included

The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site

Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 2: Compendium of Chemical Carcinogens by Target Organ - Toxnet

640 GOLD ET AL TOXICOLOGIC PATHOLOGY

results included in the compendium (Table 1) The CPDBincludes 1381 papers published in the general literaturethrough 1996 and 430 Technical Reports of the NationalCancer InstituteNational Toxicology Program (NCINTP)published through 1998 Results are reported for 6073 ex-periments on 1458 chemicals of which 738 induce tumorsin 1 or more experiments

A word of caution is necessary about the limitations ofthe CPDB Only long-term experiments meeting a set of cri-teria designed to measure tumorigenic dose-rate (TD50) areincluded therefore the CPDB does not cover all cancer testsAdditionally for the identi cation of target sites for the com-pendium we do not personally evaluate whether a compoundinduced tumors at a given site rather the opinion of the pub-lished author is used For published opinions that are notclear even after personal communication with the publishedauthor the site is not considered a target and is not reportedin the compendium

Results of all NCINTP Technical Reports are included inthe CPDB except a few for which no whole body exposure inmgkgday could be calculated because the test agent was aparticulate or the route of administration was dermal (12 13)[httpntp-serverniehsnihgov] In the compendium a siteis classi ed as a target in an NCINTP bioassay if the eval-uation in the Technical Report was ldquocarcinogenicrdquo ldquoclearrdquoor ldquosomerdquo evidence of carcinogenic activity Sites that wereevaluated as ldquoequivocalrdquo are not included (9)

In the general literature experimental designs as well asthe authorsrsquo choice of information to report are quite diverseand bioassays have been included only if they meet all of thefollowing conditions

1 Animals on test were mammals2 Administration was begun early in life (100 days of age

or less for rats mice and hamsters)3 Route of administration was diet water gavage inhala-

tion intravenous or intraperitoneal injection (ie wherethe whole body was more likely to have been exposedrather than only a speci c site as with subcutaneous in-jection or skin painting)

4 Test agent was administered alone rather than in combi-nation with other chemicals

5 Exposure was chronic with not more than 7 days betweenadministrations

6 Duration of exposure was at least one fourth the standardlife span for that species For rodents the standard lifespan is 2 years

7 Duration of experiment was at least half the standard lifespan for that species

8 Research design included a concurrent control group9 Research design included at least 5 animals per group

10 Surgical intervention was not performed11 Pathology data were reported for the number of animals

with tumors rather than the total number of tumors12 Results reported were original data rather than sec-

ondary analyses of experiments already reported by otherauthors

More details on inclusion criteria can be found in Goldand coworkers (6) and httppotencyberkeleyedutextmethodshtml

Because we have adhered strictly to the standard inclu-sion criteria bioassays of particulate or brous matters arenot in the compendium eg asbestos cigarette smoke anddusts There are no studies using a single administration ofthe test agent no experiments by skin painting subcutaneousinjection or in utero exposure and no cocarcinogenesis ex-periments For a series of NCI long-term studies in monkeyssome of the inclusion rules have been relaxed details arereported in Appendix 1 of Gold et al 1999 (2)

There is great diversity in results for different chemicalsin the CPDB eg in the number of times a chemical has beentested among the 1148 chemicals tested in rats 25 haveonly 1 test in the CPDB and 50 have 2 tests however25 chemicals have 10 or more tests For the 938 chemicalstested in mice the parallel numbers are 11 with 1 test 57with 2 tests and 15 chemicals with more than 10 tests Ofthe 738 carcinogens reported here 54 (397738) have beentested in more than 1 species In the compendium (Table 1)a target site is identi ed by a positive result in any one ex-periment in the species thus different target sites may beidenti ed from the same or different experiments Chemi-cals that are tested more often have a greater chance of nd-ing multiple target sites Results on chemicals that have notbeen evaluated as carcinogenic are ignored in the target or-gan compendium (Table 1) however detailed results of thoseexperiments are reported in the plot of the CPDB (2 3 6)httppotencyberkeleyedu

Guide to the Compendium of Target Organs for 738Carcinogens

Table 1 reports results on 738 chemicals in the CPDB thatinduce tumors in at least 1 of 35 target organs in rats micehamsters monkeys or dogs The table is organized alpha-betically by target site and within each site by species andchemical Our previously unpublished analyses of experi-mental results that will be published in a forthcoming plot ofthe CPDB are included (3)

To facilitate use of the compendium the features aredescribed below using the example of adrenal gland whichis the rst of 35 target sites in Table 1 Under adrenal gland1 chemical is listed in hamsters 8 in mice and 16 in ratsIf a chemical name is followed by a superscript (either yor z) this indicates that the CPDB includes test results inboth rats and mice for example under adrenal gland in rats2-mercaptobenzothiazole but not isomazole has a super-script Because isomazole has no superscript it only hastests in the CPDB in the species reported in this case ratsThe superscript y for 2-mercaptobenzothiazole indicatesthat the chemical has been tested in both rats and mice butinduced tumors only in the reported species in this case ratsThe superscript z for 12-dibromo-3-chloropropane (DBCP)indicates that DBCP is carcinogenic at some target site inboth rats and mice Although the superscript z does not indi-cate whether DBCP induced tumors at the same target site inboth rats and mice this can easily be determined by lookingat mice under adrenal gland for the chemical name DBCPBecause it is not there DBCP induced tumors in mice only atsites other than the adrenal gland In contrastpentachloroanisole z induced adrenal tumors in both speciesbeacuse it is listed under that site for both species Bycomparing the chemicals with superscripts listed under each

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Adr

enal

glan

dH

amst

er1

Ure

than

ez

Mou

se8

Car

bon

tetr

achl

orid

ez F

uran

z 4

4-M

ethy

lene

dian

iline

2H

Clz

Pen

tach

loro

anis

olez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y

23

45

6-P

enta

chlo

roph

enol

tec

hnic

algr

adez

p-R

osan

ilin

eH

Clz

11

2-T

rich

loro

etha

ney

Rat

16B

rom

oeth

anez

4-C

hlor

o-m

-phe

nyle

nedi

amin

ez C

obal

tsul

fate

hept

ahyd

rate

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

Die

thyl

stilb

estr

olz

Eth

ylal

coho

ly In

dolid

anI

som

azol

e2-

Mer

capt

oben

zoth

iazo

ley

Mir

exz

Pen

tach

loro

anis

olez

Phe

nolp

htha

lein

z 1

2-Pr

opyl

ene

oxid

ez C

Ip

igm

entr

ed3z

Res

erpi

nez

Ret

inol

acet

ate

Bon

eR

at5

Acr

onyc

ine

De

azac

ort

NN

-Dim

ethy

lani

liney

1-( 2

-Hyd

roxy

ethy

l)-1

-nit

roso

urea

z o-

Tolu

idin

eH

Clz

Clit

oral

pre

putia

lM

ouse

11A

ceta

ldeh

yde

met

hylf

orm

ylhy

draz

one

Ben

zene

z 1

3-B

utad

iene

z N

-n-B

utyl

-N-f

orm

ylhy

draz

ine

Dim

ethy

lvin

ylch

lori

dez

N-E

thyl

-N-f

orm

ylhy

draz

ine

glan

dH

exan

alm

ethy

lfor

myl

hydr

azon

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eP

enta

nalm

ethy

lfor

myl

hydr

azon

eN

-N-P

ropy

l-N

-for

myl

hydr

azin

eT

hio-

tepa

z

Rat

21A

cryl

amid

eC

Id

irec

tblu

e15

24

-Dia

min

oani

sole

sulf

atez

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

Glu

-P-1

z G

lu-P

-2z

Gly

cido

lz IQ

z Is

opho

rone

y M

eIQ

xz 2-

Mer

capt

oben

zoth

iazo

ley

Nal

idix

icac

idy

15-

Nap

htha

lene

diam

inez

5-N

itro-

o-a

nisi

dine

z 5-

Nit

roac

enap

hthe

nez

p-N

itro

benz

oic

acid

y 1-

Nitr

opyr

ene

CI

aci

dre

d11

41

23-

Tri

chlo

ropr

opan

ez T

rp-P

-2ac

etat

ez

Ear

Zym

balrsquos

glan

dM

ouse

3B

enze

nez

Chl

orop

rene

z C

upfe

rron

z

Rat

41A

cryl

onit

rile

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

Azo

xym

etha

neB

enze

nez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

irec

tblu

e15

N-n

-But

yl-N

-nitr

osou

rea

Chl

oram

buci

lz C

upfe

rron

z N

-1-D

iace

tam

ido

uore

ne2

4-D

iam

inoa

niso

lesu

lfat

ez 3

3-D

ichl

orob

enzi

dine

25

-Dim

etho

xy-4

-am

inos

tilb

enez

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

N-(

2-Fl

uore

nyl)

-22

2-t

riu

oroa

ceta

mid

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

Hyd

razo

benz

enez

IQz

IQH

Cl

MeI

Qxz

2-M

etho

xy-3

-am

inod

iben

zofu

ran

8-M

etho

xyps

oral

enN

-(N

-Met

hyl-

N-n

itro

soca

rbam

oyl)

-l-o

rnit

hine

44

-Met

hyle

ne-

bis(

2-ch

loro

anili

ne)

5-N

itro-

o-an

isid

inez

5-N

itroa

cena

phth

enez

N-(

9-O

xo-2

-uo

reny

l)ac

etam

ide

Phen

acet

inz

Pre

dnim

usti

neC

Ia

cid

red

114

p-R

osan

iline

HC

lz T

hio-

tepa

z 4

4-T

hiod

iani

line

z b

-Thi

ogua

nine

deox

yrib

osid

e1

23-

Tri

chlo

ropr

opan

ez V

inyl

chlo

ride

z V

inyl

uor

idez

Eso

phag

usH

amst

er2

AF-

2z N

-Nitr

oso-

N-m

ethy

lure

than

eM

ouse

8B

enzo

( a) p

yren

ez 1

2-D

ibro

moe

than

ez N

-Eth

yl-N

-nit

ro-N

-nit

roso

guan

idin

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

3-( 5

-Nit

ro-2

-fur

yl) -

imid

azo(

12-

a) p

yrid

inez

Nitr

osod

ibut

ylam

inez

N-N

itros

ohex

amet

hyle

neim

ine

Vin

ylac

etat

ez

Mon

key

1N

-Nitr

oso-

N-m

ethy

lure

az

Rat

362

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

N-n

-But

yl-N

-nitr

osou

rea

Dih

ydro

safr

olez

Dim

ethy

lvin

ylch

lori

dez

Din

itro

soho

mop

iper

azin

eZ

-Eth

yl-O

NN

-azo

xyet

hane

N-M

ethy

l-N

-nitr

o-N

-nit

roso

guan

idin

ez 3-

( 5-N

itro

-2-f

uryl

) -im

idaz

o(1

2-a

) pyr

idin

ez N

-Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-hy

drox

ypro

pyla

min

eN

itro

so-2

3-d

ihyd

roxy

prop

yl-2

-oxo

prop

ylam

ine

N-N

itro

so-(

2-hy

drox

ypro

pyl)

-(2-

hydr

oxye

thyl

) am

ine

N-N

itros

o-N

-met

hyl-

4-u

oroa

nilin

eN

itros

o-N

-met

hyl-

N-(

2-ph

enyl

) eth

ylam

ine

Nitr

oso-

12

36-

tetr

ahyd

ropy

ridi

neN

-Nit

roso

( 22

2-t

riu

oroe

thyl

) eth

ylam

ine

N-N

itros

oall

yl-2

3-d

ihyd

roxy

prop

ylam

ine

N-N

itro

soal

lyl-

2-hy

drox

ypro

pyla

min

eN

-Nit

roso

ally

l-2-

oxop

ropy

lam

ine

Nitr

osoa

myl

uret

han

Nitr

osoa

naba

sine

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

ipro

pyla

min

eN

itro

soet

hylu

reth

ane

Nit

roso

hept

amet

hyle

neim

ine

N-N

itro

som

ethy

l-2

3-di

hydr

oxyp

ropy

lam

ine

N-N

itros

omet

hyl-

2-hy

drox

ypro

pyla

min

eN

-Nit

roso

met

hyl(

2-ox

opro

pyl)

amin

e2-

Nitr

osom

ethy

lam

inop

yrid

ine

Nit

roso

met

hyla

nili

neN

-Nitr

oson

orni

cotin

e-1-

N-o

xide

N-N

itro

sopi

peri

dine

z N

-Nit

roso

thia

ldin

eN

-Nit

roso

thio

mor

phol

ine

Gal

lbla

dder

Ham

ster

1N

-Met

hyl-

N-f

orm

ylhy

draz

ine

Mou

se4

N-E

thyl

-N-f

orm

ylhy

draz

ine

N-M

ethy

l-N

-for

myl

hydr

azin

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eN

-N-P

ropy

l-N

-for

myl

hydr

azin

eM

onke

y1

Aa

toxi

nB

y 1H

arde

rian

glan

dM

ouse

19B

enze

nez

Ben

zidi

ne2

HC

l2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

13-

But

adie

nez

Cap

tafo

lz C

hlor

opre

nez

Cup

ferr

onz

Dic

hlor

oace

tyle

nez

Eth

ylen

eox

idez

Gen

tian

viol

etG

lyci

dolz

Iodi

nate

dgl

ycer

olz

Isop

rene

N-M

ethy

lola

cryl

amid

ey N

itro

met

hane

z 4

4-O

xydi

anil

inez

12

3-T

rich

loro

prop

anez

24

6-T

rini

tro-

13-

dim

ethy

l-5-

tert

-but

ylbe

nzen

eV

inyl

uor

idez

Hem

atop

oiet

icM

ouse

53A

ceta

mid

ez A

at

oxin

cru

dez

Ally

liso

vale

rate

z tr

ans-

5-A

min

o-3[

2-( 5

-nitr

o-2-

fury

l)vi

nyl] -

12

4-ox

adia

zole

2-A

min

o-4-

( p-n

itro

phen

yl) t

hiaz

ole

syst

em2-

Am

inoa

nthr

aqui

none

z 5-

Aza

cyti

dine

z A

zath

iopr

ine

Ben

zene

z 1

4-B

enzo

quin

one

Ben

zotr

ichl

orid

eB

enzo

ylhy

draz

ine

13-

But

adie

nez

12-

di-n

-But

ylhy

draz

ine

2HC

lC

apta

folz

Chl

oram

buci

lz C

hlor

inat

edpa

raf

ns( C

234

3ch

lori

ne)y

Cyc

loph

osph

amid

ez D

acar

bazi

nez

DD

Tz

Dib

rom

odul

cito

lz D

ibro

mom

anni

tolz

Est

radi

olm

usta

rdy

Eth

ylen

eox

idez

5-Fl

uoro

urac

ily Fo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

entia

nvi

olet

Hex

anam

idey

2-H

ydra

zino

-4-(

p-am

inop

heny

l)th

iazo

lez

2-H

ydra

zino

-4-

( p-n

itro

phen

yl) t

hiaz

olez

1-( 2

-Hyd

roxy

ethy

l)-1

-nit

roso

urea

z IC

RF

-159

z Is

opho

spha

mid

ez Is

opre

neM

eIQ

xz M

elph

alan

z 1-

Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

mM

ethy

lmet

hane

sulf

onat

e4

4-M

ethy

lene

dian

ilin

e2H

Clz

Met

roni

dazo

lez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hene

ster

inz

Phe

nolp

htha

lein

z Ph

IPH

Clz

Phor

bol

Proc

arba

zine

HC

lz S

trob

ane

Tetr

auo

roet

hyle

nez

Thi

o-te

paz

p-To

lylu

reay

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez U

reth

anez

CI

vat

yello

w4y

( Con

tinue

don

next

page

)

641

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Mon

key

1P

roca

rbaz

ine

HC

lz

Rat

56A

llyl

isov

aler

atez

1-A

myl

-1-n

itros

oure

aA

traz

iney

Ben

zidi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

CI

dir

ectb

lue

15

N-n

-But

yl-N

-nitr

osou

rea

Cad

miu

mch

lori

deC

hlor

ambu

cilz

Cyc

loph

osph

amid

ez D

acar

bazi

nez

13-

Dib

utyl

-1-n

itro

sour

eaD

ichl

oroa

cety

lene

z 3

3-D

ichl

orob

enzi

dine

Dic

hlor

vosz

Dim

etho

xane

33

-Dim

etho

xybe

nzid

ine-

44

-dii

socy

anat

ey 3

3-D

imet

hoxy

benz

idin

e2H

Cl

Dim

ethy

lmor

phol

inop

hosp

hora

mid

atey

2-( 2

2-D

imet

hylh

ydra

zino

) -4-

( 5-n

itro-

2-fu

ryl)

thia

zole

Eth

ylen

eox

idez

Form

alde

hyde

z Fo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z F

uran

z G

lyci

dolz

FD

ampC

gree

nno

1y

FDamp

Cgr

een

no2

y H

emat

oxyl

in2

-Hyd

razi

no-4

-(p-

amin

ophe

nyl)

thia

zole

z H

ydro

quin

onez

1-( 2

-Hyd

roxy

ethy

l)-1

-nit

roso

urea

z Io

dina

ted

glyc

erol

z L

asio

carp

ine

2-M

erca

ptob

enzo

thia

zole

y M

etep

aM

ethy

lter

t-bu

tyle

ther

z M

irex

z l-

5-M

orph

olin

omet

hyl-

3-[(

5-ni

trof

urfu

ryli

dene

) am

ino]

-2-o

xazo

lidi

none

H

Cl

Nit

rite

sod

ium

y N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez o-

Nit

roan

isol

ez 1-

[(5-

Nitr

ofur

fury

liden

e)am

ino]

-2-i

mid

azol

idin

one

1-N

itro

pyre

neN

itros

o-N

-met

hyl-

N-(

2-ph

enyl

) eth

ylam

ine

N-N

itros

odie

than

olam

ine

PhIP

HC

lz P

roca

rbaz

ine

HC

lz P

ropa

nesu

ltone

N-P

ropy

l-N

-nit

roso

urea

FD

ampC

red

no2

FD

ampC

red

no4

y Te

trac

hlor

oeth

ylen

ez Te

tra

uoro

ethy

lene

z T

hio-

tepa

z 2

46-

Tri

chlo

roph

enol

z T

rp-P

-2ac

etat

ez

Kid

ney

Ham

ster

1B

rom

ate

pota

ssiu

mz

Mou

se26

o-B

enzy

l-p-

chlo

roph

enol

y 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z B

rom

odic

hlor

omet

hane

z 1

3-B

utad

iene

z 1

2-di

-n-B

utyl

hydr

azin

e2H

Cl

Caf

feic

acid

z C

hlor

ofor

mz

Chl

orop

rene

z D

amin

ozid

ez 2

4-D

iam

inop

heno

l2H

Cly

Dic

hlor

oace

tyle

nez

24-

Din

itrot

olue

ne( c

onta

inin

g1

0-1

52

6-di

nitr

otol

uene

)zH

ydro

quin

onez

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z 3-

Hyd

roxy

-p-b

utyr

ophe

neti

dide

L

ead

acet

ate

basi

cz M

ercu

rym

ethy

lchl

orid

eN

itril

otri

acet

icac

idz

Och

rato

xin

Az

Phe

nace

tinz

CI

pig

men

tred

3z St

rept

ozot

ocin

z T

ris(

2-ch

loro

ethy

l)ph

osph

atez

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez V

inyl

iden

ech

lori

dey

Mon

key

1C

ycas

inan

dm

ethy

lazo

xym

etha

nola

ceta

teR

at86

A

atox

inB

1y 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 1-

Am

ino-

2-m

ethy

lant

hraq

uino

nez

2-A

min

o-5-

( 5-n

itro-

2-fu

ryl)

-13

4-o

xadi

azol

e2-

Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

e2-

Am

ino-

4-ni

trop

heno

ly 2-

Am

ino-

5-ni

trot

hiaz

oley

o-A

nisi

dine

HC

lz A

rist

oloc

hic

acid

so

dium

salt

( 77

AA

I21

A

AII

) A

zoxy

met

hane

Bar

bita

lso

dium

Ben

zofu

ranz

Bro

mat

epo

tass

ium

z B

rom

odic

hlor

omet

hane

z te

rt-B

utyl

alco

holz

Caf

feic

acid

z C

apta

folz

Cap

tanz

Chl

orin

ated

para

fns

( C12

60

chlo

rine

)zC

hlor

ofor

mz

3-( p

-Chl

orop

heny

l)-1

1-d

imet

hylu

reay

Chl

orop

rene

z C

hlor

otha

loni

ly C

inna

myl

anth

rani

late

z C

itrin

inC

oum

arin

z D

ichl

oroa

cety

lene

z 1

4-D

ichl

orob

enze

nez

Die

thyl

acet

amid

e3

4-D

ihyd

roco

umar

inz

Dim

etho

xane

Dim

ethy

lmet

hylp

hosp

hona

tey

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

N-4

-(4

-Flu

orob

iphe

nyl)

acet

amid

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lyci

neH

exac

hlor

obut

adie

ne

Hex

achl

oroe

than

ez H

exam

ethy

lmel

amin

e2-

Hyd

razi

no-4

-(5-

nitr

o-2-

fury

l)th

iazo

lez

Hyd

roqu

inon

ez 1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

Isop

horo

ney

Lea

dac

etat

ey L

ead

acet

ate

basi

cz d-

Lim

onen

ey 2-

Met

hoxy

-3-a

min

odib

enzo

fura

n8-

Met

hoxy

psor

alen

Z-M

ethy

l-O

NN

-azo

xyet

hane

Met

hylt

ert-

buty

leth

erz

N-(

N-M

ethy

l-N

-nit

roso

carb

amoy

l)-l

-orn

ithi

nea

-Met

hylb

enzy

lalc

ohol

y M

irex

z l-

5-M

orph

olin

omet

hyl-

3-[(

5-ni

trof

urfu

rylid

ene)

amin

o]-2

-oxa

zolid

inon

eH

Cl

Nit

rilo

tria

ceti

cac

idz

Nit

rilo

tria

cetic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

3-( 5

-Nitr

o-2-

fury

l)-i

mid

azo(

12-

a) p

yrid

inez

N-[

3-( 5

-Nitr

o-2-

fury

l)-1

24

-oxa

diaz

ole-

5-yl

] -m

ethy

l]ac

etam

ide

N-[

5-( 5

-Nitr

o-2-

fury

l)-1

34

-thi

adia

zol-

2-yl

] ace

tam

idez

o-N

itro

anis

olez

Nitr

oben

zene

z 2-

Nit

ro

uore

ne

1-[(

5-N

itrof

urfu

rylid

ene)

amin

o]hy

dant

oinz

1-N

itro

so-1

-hyd

roxy

ethy

l-3-

chlo

roet

hylu

rea

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

imet

hyla

min

ez N

-Nit

roso

pyrr

olid

inez

Och

rato

xin

Az

CI

aci

dor

ange

3y N

-Oxy

diet

hyle

neth

ioca

rbam

yl-N

-oxy

diet

hyle

nesu

lfen

amid

eP

hena

cetin

z Ph

enaz

one

Phen

olph

thal

einz

Phen

ylbu

tazo

nez

o-Ph

enyl

phen

ate

sodi

umy

Que

rcet

iny

Salic

ylaz

osul

fapy

ridi

nez

Str

epto

zoto

cinz

Tetr

achl

oroe

thyl

enez

Tetr

auo

roet

hyle

nez

Tetr

ahyd

rofu

ranz

12

3-T

rich

loro

prop

anez

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylch

lori

dez

Lar

gein

test

ine

Ham

ster

51

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

Hyd

razi

nez

Met

hylh

ydra

zine

Ure

than

ezM

ouse

1C

apsa

icin

Rat

32A

at

oxin

B1y

1-A

llyl

-1-n

itros

oure

a1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z A

myl

opec

tin

sulf

ate

Azo

xym

etha

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

te

chni

calg

rade

z C

Id

irec

tblu

e15

Bro

mod

ichl

orom

etha

nez

N-N

-But

yl-n

-nitr

osou

rea

Car

rage

enan

aci

d-de

grad

edC

hrys

azin

z D

extr

ansu

lfat

eso

dium

( DS-

M-1

) 3

3-D

imet

hoxy

benz

idin

e2H

Cl

33

-Dim

ethy

lben

zidi

ne2

HC

lz Z

-Eth

yl-O

NN

-azo

xym

etha

ne1

-Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

Glu

-P-1

z G

lu-P

-2z

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

IQz

o-N

itro

anis

olez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

Phe

nazo

pyri

dine

HC

lz P

hIP

HC

lz C

Ia

cid

red

114

44

-Thi

odia

nilin

ez T

ribr

omom

etha

ney

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez

Liv

erD

og2

33

-Dic

hlor

oben

zidi

ne4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line

)H

amst

er16

2-A

cety

lam

ino

uore

nez

pp

-DD

Ey

12-

Dim

ethy

lhyd

razi

ne2

HC

lH

exac

hlor

oben

zene

z H

ydra

zine

sulf

atez

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z N

-Met

hyl-

N-f

orm

ylhy

draz

ine

Met

hylh

ydra

zine

Met

hyln

itros

amin

o-N

N-d

imet

hyle

thyl

amin

eN

-Nitr

oso-

13-

oxaz

olid

ine

Nit

roso

-2-o

xopr

opyl

etha

nola

min

eN

-Nitr

osoa

llyl-

2-ox

opro

pyla

min

eN

-Nit

roso

azet

idin

eN

-Nit

roso

mor

phol

ine

N-N

itros

opip

erid

inez

N-N

itros

opyr

rolid

inez

Mou

se23

1A

-a-C

Ace

tam

inop

henz

2-A

cety

lam

ino

uore

nez

Aci

uor

fen

Ald

rinz

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

min

o-2-

met

hyla

nthr

aqui

none

z 2-

Am

inoa

nthr

aqui

none

z 4-

Am

inod

iphe

nyl

2-A

min

odip

heny

lene

oxid

e3-

Am

inot

riaz

olez

Ara

mite

z A

rocl

or12

54y

Aur

amin

e-O

z B

enzi

dine

2H

Cl

Ben

zofu

ranz

Ben

zyla

ceta

tey

3-B

enzy

lsyd

none

-4-a

ceta

mid

ez B

is( 2

-chl

oro-

1-m

ethy

leth

yl) e

ther

tec

hnic

algr

adey

Bis

-2-c

hlor

oeth

ylet

her

Bis

-2-h

ydro

xyet

hyld

ithio

carb

amic

acid

pot

assi

umC

Id

irec

tbla

ck38

CI

dir

ectb

lue

218z

HC

blue

no1

z H

Cbl

ueno

1( p

uri

ed)

Bro

mod

ichl

orom

etha

nez

13-

But

adie

nez

But

ylat

edhy

drox

ytol

uene

y 1

1-di

-n-B

utyl

hydr

azin

eC

apta

folz

Car

bazo

le

Car

bon

tetr

achl

orid

ez C

hlor

alhy

drat

eC

hlor

ambe

ny C

hlor

dane

tec

hnic

algr

adey

Chl

oren

dic

acid

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

1-

Chl

oro-

2-ni

trob

enze

ney

1-C

hlor

o-4-

nitr

oben

zene

y 4-

Chl

oro-

m-p

heny

lene

diam

inez

4-C

hlor

o-o-

phen

ylen

edia

min

ez 5-

Chl

oro-

o-to

luid

iney

642

[ 4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

] ace

ticac

idz

4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

( N-b

-hyd

roxy

ethy

l)ac

etam

idez

Chl

oroa

ceta

ldeh

yde

p-C

hlor

oani

line

HC

lz C

hlor

oben

zila

tey

Chl

orod

ibro

mom

etha

ney

Chl

orof

orm

z C

hlor

opre

nez

Chr

ysaz

inz

CI-

924

Cin

nam

ylan

thra

nila

tez

Cip

ro

brat

ez C

lobu

zari

ty C

ompo

und

LY17

1883

Cou

mar

inz

p-C

resi

dine

z C

upfe

rron

z C

ycla

mat

eso

dium

y C

yclo

chlo

roti

neC

ypro

tero

neac

etat

ep

p-D

DD

y p

p-D

DE

y D

DT

z D

ialla

te2

4-D

iam

inot

olue

nez

24-

Dia

min

otol

uene

2H

Clz

35-

Dic

hlor

o-( N

-11

-dim

ethy

l-2-

prop

ynyl

) ben

zam

ide

26-

Dic

hlor

o-p-

phen

ylen

edia

min

ey D

ichl

oroa

cetic

acid

z 1

4-D

ichl

orob

enze

nez

12-

Dic

hlor

opro

pane

y D

icof

oly

Die

ldri

nz D

ifta

lone

34

-Dih

ydro

coum

arin

z D

ihyd

rosa

frol

ez 2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 1

1-D

imet

hylh

ydra

zine

y 1

4-D

ioxa

nez

55-

Dip

heny

lhyd

anto

iny

Dip

yron

ey D

oxyl

amin

esu

ccin

atez

Est

rago

led

l-E

thio

nine

z o-

Eth

oxyb

enza

mid

eN

-Eth

yl-N

-for

myl

hydr

azin

eE

thyl

ene

imin

eE

thyl

ene

thio

urea

z 2-

Eth

ylhe

xano

ly di

( 2-E

thyl

hexy

l)ad

ipat

ey di

( 2-E

thyl

hexy

l)ph

thal

atez

4-F

luor

o-4-

amin

odip

heny

lF

uran

z Fu

rfur

alz

Gen

tian

viol

etG

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

Gri

seof

ulvi

nH

CD

Dm

ixtu

rez

Hep

tach

lory

Hex

achl

orob

enze

nez

a-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

z b

-12

34

56

-Hex

achl

oroc

yclo

hexa

nec

-12

34

56

-Hex

achl

oroc

yclo

hexa

ney

Hex

achl

oroc

yclo

hexa

ne

tech

nica

lgra

deH

exac

hlor

oeth

anez

Hex

anal

met

hylf

orm

ylhy

draz

one

Hyd

razi

nesu

lfat

ez H

ydra

zobe

nzen

ez H

ydro

quin

onez

N-H

ydro

xy-2

-ac

etyl

amin

ouo

rene

z 1

-Hyd

roxy

estr

agol

e2-

Hyd

roxy

ethy

lhyd

razi

ne1

-Hyd

roxy

safr

olez

IQz

Ison

iazi

dz Is

opre

neK

epon

ez L

eupe

ptin

Lov

asta

tinL

uteo

skyr

inM

alon

alde

hyde

sod

ium

saltz

MeA

-a-C

acet

atez

MeI

QM

eIQ

xz M

ethi

dath

ion

3-M

etho

xy-4

-am

inoa

zobe

nzen

eM

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z N

-Met

hyl-

N-f

orm

ylhy

draz

ine

3-M

ethy

lbut

anal

met

hylf

orm

ylhy

draz

one

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nili

ne)

2HC

ly M

ethy

lene

chlo

ride

z 4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Met

hylh

ydra

zine

N-M

ethy

lola

cryl

amid

ey M

ethy

lphe

nida

teH

Cly

Mic

hler

rsquoske

tone

z M

irex

z 1

5-N

apht

hale

nedi

amin

ez 2-

Nap

hthy

lam

inez

Nit

hiaz

idez

3-N

itro-

p-ac

etop

hene

tidey

5-N

itro-

o-an

isid

inez

2-N

itro

-p-p

heny

lene

diam

iney

5-N

itro

-o-t

olui

dine

y 5-

Nitr

oace

naph

then

ez o-

Nitr

oani

sole

z N

itrob

enze

nez

6-N

itrob

enzi

mid

azol

ey N

itro

fenz

Nit

rom

etha

nez

Nitr

osod

ibut

ylam

inez

N-N

itros

odim

ethy

lam

inez

p-N

itros

odip

heny

lam

inez

N-N

itro

sohe

xam

ethy

lene

imin

eN

-Nit

roso

pipe

ridi

nez

Non

abro

mob

iphe

nyl

Och

rato

xin

Az

Oxa

zepa

my

44

-Oxy

dian

iline

z Pe

ntac

hlor

oeth

aney

Pent

achl

oron

itrob

enze

ney

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y 2

34

56-

Pen

tach

loro

phen

olt

echn

ical

grad

ez P

enta

nalm

ethy

lfor

myl

hydr

azon

eP

hena

zopy

ridi

neH

Clz

Phe

noba

rbit

aly

Phen

obar

bita

lso

dium

z Ph

enyl

buta

zone

z o-

Phen

ylen

edia

min

e2H

Clz

Pipe

rony

l-bu

toxi

dez

Pipe

rony

lsul

foxi

dey

Poly

brom

inat

edbi

phen

ylm

ixtu

rez

Prob

enec

idy

N-N

-Pro

pyl-

N-f

orm

ylhy

draz

ine

Damp

Cre

dno

5z

Rif

ampi

ciny

Rip

azep

amy

p-R

osan

iline

HC

lz S

afro

lez

Sali

cyla

zosu

lfap

yrid

inez

Sel

eniu

mdi

ethy

ldith

ioca

rbam

ate

Sel

eniu

msu

lde

z S

trob

ane

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

11

12-

Tetr

achl

oroe

than

ey 1

12

2-Te

trac

hlor

oeth

aney

Tetr

achl

oroe

thyl

enez

Tetr

achl

orvi

npho

sy Te

tra

uoro

-m-p

heny

lene

diam

ine

2HC

ly Te

tra

uoro

ethy

lene

z Te

trah

ydro

fura

nz T

hioa

ceta

mid

ez 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

m-T

olui

dine

HC

ly o-

Tolu

idin

eH

Clz

p-To

luid

ine

HC

ly To

xaph

eney

T-2

toxi

nT

riam

tere

ney

Tri

chlo

roac

etic

acid

y 2

46-

Tri

chlo

roan

iline

y 1

12-

Tri

chlo

roet

hane

y T

rich

loro

ethy

lene

z T

rich

loro

ethy

lene

( wit

hout

epic

hlor

ohyd

rin)

y 2

46-

Tri

chlo

roph

enol

z 1

23-

Tri

chlo

ropr

opan

ez T

ri

ural

int

echn

ical

grad

ey 2

45-

Tri

met

hyla

nili

nez

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nilin

eH

Clz

24

6-T

rini

tro-

13-

dim

ethy

l-5-

tert

-but

ylbe

nzen

eT

ris(

2-ch

loro

ethy

l)ph

osph

atez

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez T

ris(

2-et

hylh

exyl

) pho

spha

tey

Trp

-P-1

acet

atez

Trp

-P-2

acet

atez

Ure

than

ez V

inyl

carb

amat

eV

inyl

uo

ride

z 2

5-X

ylid

ine

HC

lz C

Id

ispe

rse

yell

ow3z

Zea

rale

none

y

Mon

key

8A

ato

xin

B1y

Cyc

asin

and

met

hyla

zoxy

met

hano

lace

tate

IQ

z N

-Nitr

osod

ieth

ylam

ine

N-N

itro

sodi

prop

ylam

ine

N-N

itro

sopi

peri

dine

z S

teri

gmat

ocys

tinz

Ure

than

ez

Rat

206

Ace

tam

idez

Ace

tam

inop

henz

Ace

toxi

me

2-A

cety

lam

ino

uore

nez

A

atox

icol

A

atox

inB

y 1A

at

oxin

cru

dez

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

min

o-2-

met

hyla

nthr

aqui

none

z 2-

Am

inoa

nthr

aqui

none

z o-

Am

inoa

zoto

luen

ey 11

-Am

inou

ndec

anoi

cac

idy

Ara

mit

ez A

rocl

or12

60A

uram

ine-

Oz

Azo

xym

etha

neB

emit

radi

ne

Ben

zidi

ne3

-Ben

zyls

ydno

ne-4

-ace

tam

idez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

CI

dir

ectb

lue

15

Bro

mod

ichl

orom

etha

nez

Bud

eson

ide

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Chl

oren

dic

acid

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 2-

Chl

oro-

5-( 3

5-d

imet

hylp

iper

idin

osul

phon

yl) b

enzo

icac

id[

4-C

hlor

o-6-

( 23

-xy

lidi

no) -

2-py

rim

idin

ylth

io] a

ceti

cac

idz

4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

( N-b

-hyd

roxy

ethy

l)ac

etam

idez

Chl

orob

enze

ney

Chl

orof

orm

z 3-

( p-C

hlor

ophe

nyl)

-11

-dim

ethy

lure

ay C

ipro

bra

tez

Cliv

orin

eC

lob

rate

y C

loph

enA

30C

oum

arin

z p-

Cre

sidi

nez

Cro

tona

ldeh

yde

Cup

ferr

onz

Cyc

lope

ntan

one

oxim

eD

DT

z D

ecab

rom

odip

heny

loxi

dey

Deh

ydro

epia

ndro

ster

one

Deh

ydro

epia

ndro

ster

one

acet

ate

24-

Dia

min

otol

uene

z 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ibro

moe

than

ez D

ichl

oroa

ceti

cac

idz

Dic

hlor

oace

tyle

nez

NN

-Die

thyl

-4-(

4-[

pyri

dyl-

1-o

xide

] azo

) ani

line

Die

thyl

stil

best

rolz

Dim

etho

xane

3

3-D

imet

hoxy

benz

idin

e2H

Cl

56-

Dim

etho

xyst

erig

mat

ocys

tinN

N-D

imet

hyl-

4-am

inoa

zobe

nzen

e6-

Dim

ethy

lam

ino-

44-

diph

enyl

-3-h

epta

nola

ceta

teH

Cly

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hyln

itram

ine

Din

itros

ohom

opip

eraz

ine

26-

Din

itro

tolu

ene

24-

Din

itrot

olue

ne( c

onta

inin

g1

0-1

52

6-di

nitr

otol

uene

)z

Din

itrot

olue

net

echn

ical

grad

e( 2

4( 7

7) -

and

26

( 19

) -)

14-

Dio

xane

z D

ipen

tyln

itro

sam

ine

Dox

ylam

ine

succ

inat

ez E

thin

yles

trad

iol

Eth

ioni

ne

dl-E

thio

nine

z 4-

Eth

oxy-

phen

ylur

eaE

thyl

alco

holy

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neE

thyl

ene

thio

urea

z di

( 2-E

thyl

hexy

l)ph

thal

atez

Flu

cona

zole

y N

-(2-

Flu

oren

yl) -

22

2-tr

iuo

roac

etam

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

Fum

onis

inB

1F

uran

z Fu

rfur

alz

Glu

-P-1

z G

lu-P

-2z

FDamp

Cgr

een

no1

y H

CD

Dm

ixtu

rez

Hex

achl

orob

enze

nez

a-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

z H

ydra

zine

z H

ydra

zine

sulf

atez

Hyd

razo

benz

enez

Hyd

roch

loro

uor

ocar

bon

123

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z 1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-nitr

oso-

3-ch

loro

ethy

lure

a1

-Hyd

roxy

safr

olez

IQz

IQH

Cl

Ison

iazi

dz K

epon

ez L

asio

carp

ine

MeA

-a-C

acet

atez

MeI

Qxz

Met

hapy

rile

neH

Cl

Z-M

ethy

l-O

NN

-azo

xyet

hane

Met

hylc

arba

mat

ey M

ethy

lclo

fena

pate

z 3

-Met

hyl-

4-di

met

hyla

min

oazo

benz

ene

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

4-( 4

-N-M

ethy

l-N

-nit

rosa

min

osty

ryl)

quin

olin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line

) 4

4-M

ethy

lene

dian

ilin

e2H

Clz

4-( M

ethy

lnit

rosa

min

o)-1

-(3-

pyri

dyl)

-1-(

buta

none

) M

etro

nida

zole

z M

ichl

errsquos

keto

nez

Mir

exz

Mon

ocro

tali

neN

afen

opin

Nit

rite

sod

ium

y N

itrob

enze

nez

2-N

itro

buta

ne2

-Nit

ro

uore

ne3

-Nit

rope

ntan

eN

-Nitr

oso-

bis-

( 44

4-t

ri

uoro

-N-b

utyl

) am

ine

1-N

itros

o-5

6-di

hydr

oura

cil

N-N

itro

so-2

3-d

ihyd

roxy

prop

ylet

hano

lam

ine

1-N

itros

o-1-

hydr

oxye

thyl

-3-c

hlor

oeth

ylur

ea1

-Nitr

oso-

1-( 2

-hyd

roxy

prop

yl) -

3-ch

loro

ethy

lure

aN

-Nitr

oso-

( 2-h

ydro

xypr

opyl

) -( 2

-hyd

roxy

ethy

l)am

ine

N-N

itros

o-N

-met

hyl-

N-d

odec

ylam

ine

Nit

roso

-N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

e

( Con

tinue

don

next

page

)

643

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

N-N

itro

so-N

-met

hyld

ecyl

amin

e3-

Nit

roso

-2-o

xazo

lidin

one

Nit

roso

-2-o

xopr

opyl

etha

nola

min

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osoa

llyl

etha

nola

min

eN

-Nit

roso

bis(

2-ox

opro

pyl)

amin

eN

itro

sodi

buty

lam

inez

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

imet

hyla

min

ez p-

Nitr

osod

iphe

nyla

min

ez N

-Nit

roso

dipr

opyl

amin

eN

itros

odod

ecam

ethy

lene

imin

eN

-Nit

roso

ephe

drin

eN

itro

soet

hylm

ethy

lam

ine

Nitr

osoh

epta

met

hyle

neim

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

met

hyl-

( 2-h

ydro

xyet

hyl)

amin

eN

-Nitr

osom

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

-Nitr

osom

ethy

l(2-

oxop

ropy

l)am

ine

N-N

itro

som

ethy

l-( 2

-tos

ylox

yeth

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eN

-Nit

roso

mor

phol

ine

N-N

itros

opip

erid

inez

N-N

itro

sopy

rrol

idin

ez N

-Nit

roso

thia

ldin

eo-

Nit

roso

tolu

ene

Nor

lest

rinz

N-(

9-O

xo-2

-uo

reny

l)ac

etam

ide

44

-Oxy

dian

iline

z 2

34

56-

Pent

achl

orop

heno

lte

chni

calg

rade

z P

etas

iten

ine

Phe

noba

rbit

als

odiu

mz

1-P

heny

lazo

-2-n

apht

holy

o-P

heny

lene

diam

ine

2HC

lz P

iper

onyl

buto

xide

z P

olyb

rom

inat

edbi

phen

ylm

ixtu

rez

Pre

dnis

olon

eP

yril

amin

em

alea

tey

CI

aci

dre

d11

4C

Ip

igm

entr

ed3z

Damp

Cre

dno

5z

Damp

Cre

dno

9y

FD

ampC

red

no1

p-

Ros

anili

neH

Clz

Saf

role

z Se

leni

umsu

lde

z Se

nkir

kine

Ste

rigm

atoc

ystin

z S

ymph

ytin

eTa

mox

ifen

citr

atez

Telo

neII

tec

hnic

algr

adez

33

44

-Te

traa

min

obip

heny

l4H

Clz

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

auo

roet

hyle

nez

Thi

oace

tam

idez

44

-Thi

odia

nilin

ez To

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

Tri

amci

nolo

neac

eton

ide

24

5-T

rim

ethy

lani

line

z 2

45-

Tri

met

hyla

nili

neH

Clz

24

6-T

rim

ethy

lani

line

HC

lz T

rini

trog

lyce

rin

Trp

-P-1

acet

atez

Trp

-P-2

acet

atez

Vin

ylac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

CI

dis

pers

eye

llow

3z

Tre

esh

rew

1A

ato

xin

B1y

Lun

gH

amst

er3

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

1-N

itro

so-3

45

-tri

met

hylp

iper

azin

eM

ouse

116

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-is

onic

otin

oylh

ydra

zine

A

llyl

hydr

azin

eH

Cl

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

Are

coli

neH

Cl

5-A

zacy

tidi

nez

Ben

zene

z B

enzo

fura

nz B

enzo

tric

hlor

ide

Ben

zoyl

hydr

azin

eB

enzy

lhyd

razi

ne2

HC

l2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 2-c

hlor

o-1-

met

hyle

thyl

) eth

er

tech

nica

lgra

dey

Bis

-(ch

loro

met

hyl)

ethe

rz 1

3-B

utad

iene

z N

-n-B

utyl

-N-f

orm

ylhy

draz

ine

But

ylat

edhy

drox

ytol

uene

y 1

1-di

-n-B

utyl

hydr

azin

en-

But

ylhy

draz

ine

HC

l1

2-di

-N-B

utyl

hydr

azin

e2H

Cl

Caf

feic

acid

z C

arba

myl

hydr

azin

eH

Cl

1-C

arba

myl

-2-p

heny

lhyd

razi

neC

hlor

ambu

cilz

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z C

oum

arin

z C

yclo

phos

pham

idez

Dac

arba

zine

z D

amin

ozid

ez p

p-D

DD

y D

DT

z 1

1-D

iall

ylhy

draz

ine

12-

Dia

llyl

hydr

azin

e2H

Cl

Dib

enz(

ah)

anth

race

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

Dib

rom

odul

cito

lz 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

12-

Dic

hlor

oeth

anez

12-

Dif

orm

ylhy

draz

ine

Dih

ydro

safr

olez

25-

Dim

etho

xy-4

-am

inos

tilbe

nez

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

a-E

cdys

one

Est

radi

olm

usta

rdy

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylen

eim

ine

Eth

ylen

eox

idez

Eth

ylhy

draz

ine

HC

l5-

Flu

orou

raci

ly Fo

rmyl

hydr

azin

eG

lyci

dolz

c-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

y H

exan

alm

ethy

lfor

myl

hydr

azon

eH

ydra

zine

z H

ydra

zine

sulf

atez

IQz

Isob

utyl

nitr

itez

Ison

iazi

dz Is

onic

otin

icac

idva

nilly

liden

ehyd

razi

de

Isop

rene

Lov

asta

tinM

eIQ

xz M

elph

alan

z 1-

Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m

N-M

ethy

l-N

-for

myl

hydr

azin

eM

ethy

lmet

hane

sulf

onat

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eM

ethy

lene

chlo

ride

z M

ethy

lhyd

razi

ne

Met

hylh

ydra

zine

sulf

ate

( N-6

) -( M

ethy

lnit

roso

) ade

nine

(N

-6) -

( Met

hyln

itro

so) a

deno

sine

N-M

ethy

lola

cryl

amid

ey M

etro

nida

zole

z M

olyb

denu

mtr

ioxi

dey

Mon

oace

tylh

ydra

zine

Nap

htha

lene

15

-Nap

htha

lene

diam

inez

Nic

otin

icac

idhy

draz

ide

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez 3-

Nitr

o-3-

hexe

nez

Nit

robe

nzen

ez N

itrom

etha

nez

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

dim

ethy

lam

inez

N-N

itros

ohex

amet

hyle

neim

ine

N-N

itro

sopi

peri

dine

z O

zone

y Pe

ntan

alm

ethy

lfor

myl

hydr

azon

en-

Pen

tylh

ydra

zine

HC

lPh

enes

teri

nz Ph

enyl

ethy

lhyd

razi

nesu

lfat

eP

roca

rbaz

ine

HC

lz N

-N-P

ropy

l-N

-for

myl

hydr

azin

eP

ropy

lhyd

razi

neH

Cl

Sel

eniu

msu

lde

z S

trep

tozo

toci

nz Su

lfal

late

z Te

lone

IIt

echn

ical

grad

ez 3

34

4-T

etra

amin

obip

heny

l4H

Clz

Tetr

anitr

omet

hane

z T-

2to

xin

Tri

chlo

roet

hyle

nez

Tri

ura

lint

echn

ical

grad

ey 2

45-

Tri

met

hyla

nilin

eH

Clz

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez U

reth

anez

Vin

ylch

lori

dez

Vin

ylu

orid

ez V

inyl

iden

ech

lori

dey

24-

Xyl

idin

eH

Cly

Mon

key

1U

reth

anez

Rat

551-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro

-2-f

uryl

) -1

34-

oxad

iazo

le2

-Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-5-

nitr

othi

azol

ey 1-

Am

yl-1

-nitr

osou

rea

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is-(

chlo

rom

ethy

l)et

herz

HC

blue

no1

z B

rom

oeth

anez

N-n

-But

yl-N

-nit

roso

urea

Cad

miu

mch

lori

deC

adm

ium

sulp

hate

( 11

) 1-

Chl

oroe

thyl

nitr

oso-

3-( 2

-hyd

roxy

prop

yl) u

rea

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z 1

2-D

ibro

moe

than

ez D

imet

hylh

ydro

gen

phos

phit

ey tr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-

[ 2-(

5-ni

tro-

2-fu

ryl)

viny

l] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

12-

Epo

xybu

tane

y 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

Hyd

razi

nez

Hyd

razi

nesu

lfat

ez 1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

Isob

utyl

nitr

itez

Ison

iazi

dz 4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4-

( Met

hyln

itros

amin

o)-1

-(3-

pyri

dyl)

-1-b

utan

ol4

-(M

ethy

lnit

rosa

min

o)-1

-(3-

pyri

dyl)

-1-(

buta

none

) N

-[ 3

-(5-

Nitr

o-2-

fury

l)-

12

4-ox

adia

zole

-5-y

l] -m

ethy

lace

tam

ide

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

3-N

itro-

3-he

xene

z 5-

Nitr

oace

naph

then

ez N

-Nit

roso

-bis

-(4

44-

tri

uoro

-N-b

utyl

) am

ine

N-N

itros

o-N

-met

hyl-

N-d

odec

ylam

ine

N-N

itros

o-N

-met

hyl-

N-t

etra

decy

lam

ine

N-N

itro

so-N

-met

hyld

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

lure

az N

-Nitr

osob

is( 2

-hyd

roxy

prop

yl)

amin

eN

-Nitr

osob

is-2

3-d

ihyd

roxy

prop

ylam

ine

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itros

odim

ethy

lam

inez

N-N

itro

soep

hedr

ine

Nitr

osoe

thyl

met

hyla

min

eN

-Nit

roso

met

hyl

N-N

itro

som

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eC

Ia

cid

red

114

Sod

ium

dich

rom

ate

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

anit

rom

etha

nez

24

5-T

rim

ethy

lani

line

z 2

46-

Tri

met

hyla

nili

neH

Clz

Vin

ylch

lori

dez

Mam

mar

ygl

and

Dog

1Ly

nest

reno

lH

amst

er1

Vin

ylch

lori

dez

Mou

se24

5-A

zacy

tidin

ez B

enze

nez

CI

dir

ectb

lack

381

3-B

utad

iene

z C

alci

fero

lC

hlor

opre

nez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Die

thyl

stilb

estr

olz

a-E

cdys

one

Est

radi

olE

thyl

ene

oxid

ez F

uros

emid

ey G

lyci

dolz

Gri

seof

ulvi

nIs

onia

zidz

Ison

icot

inic

acid

vani

llylid

eneh

ydra

zide

( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Nitr

oben

zene

z R

eser

pine

z Su

lfal

late

z V

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y

644

Rat

102

4-A

cety

lam

inob

iphe

nyl

2-A

cety

lam

ino

uore

nez

Acr

onyc

ine

Acr

ylam

ide

Acr

ylon

itri

leA

F-2

z 1-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro-

2-fu

ryl)

-13

4-

oxad

iazo

le2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

e2-

Am

ino-

5-ni

trot

hiaz

oley

4-A

min

odip

heny

lHC

l1-

Am

yl-1

-nit

roso

urea

Atr

azin

ey B

emit

radi

ne

Ben

zidi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

4-B

is( 2

-hyd

roxy

ethy

l)am

ino-

2-( 5

-nit

ro-2

-thi

enyl

) qui

nazo

line

13-

But

adie

nez

N-n

-But

yl-N

-nitr

osou

rea

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Car

boxy

met

hyln

itros

oure

aC

hlor

ambu

cilz

Chl

orop

rene

z C

ytem

bena

y D

acar

bazi

nez

N-1

-Dia

ceta

mid

ouo

rene

46

-Dia

min

o-2-

( 5-n

itro-

2-fu

ryl)

-S-t

riaz

ine

24-

Dia

min

oani

sole

sulf

atez

24-

Dia

min

otol

uene

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dib

rom

oman

nito

lz 1

3-D

ibut

yl-1

-nit

roso

urea

33

-Dic

hlor

oben

zidi

ne1

2-D

ichl

oroe

than

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

12-

Dim

ethy

l-5-

nitr

oim

idaz

ole

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lam

inoe

thyl

nitr

osoe

thyl

urea

nitr

ite

salt

33

-Dim

ethy

lben

zidi

ne2

HC

lz 2-

( 22

-Dim

ethy

lhyd

razi

no) -

4-( 5

-nitr

o-2-

fury

l)th

iazo

le

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

24-

Dio

xane

z 1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

6-di

nitr

otol

uene

)zN

-(2-

Fluo

reny

l)-2

22

-tri

uo

roac

etam

ide

Form

icac

id2-

( 4-m

ethy

l-2-

thia

zoly

l)hy

draz

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-

thia

zoly

l] hyd

razi

dez

Gly

cido

lz H

exam

ethy

lmel

amin

eN

-Hex

ylni

tros

oure

a2-

Hyd

razi

no-4

-(p-

amin

ophe

nyl)

thia

zole

z 2-

Hyd

razi

no-4

-( 5

-nit

ro-2

-fur

yl) t

hiaz

olez

2-H

ydra

zino

-4-(

p-ni

trop

heny

l)th

iazo

lez

Hyd

razo

benz

enez

1-( 2

-Hyd

roxy

ethy

l)-3

-[( 5

-nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

e1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

1-(

2-H

ydro

xyet

hyl)

-1-n

itros

oure

az In

dom

etha

cin

IQz

IQH

Cl

Ison

iazi

dz 2-

Met

hoxy

-3-a

min

odib

enzo

fura

n4-

Met

hyl-

1-[(

5-ni

trof

urfu

rylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

-(N

-Met

hyl-

N-n

itro

soca

rbam

oyl)

-l-o

rnit

hine

3-M

ethy

lcho

lant

hren

e4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line)

Met

hyle

nech

lori

dez

Met

roni

dazo

lez

l-5-

Mor

phol

inom

ethy

l-3-

[(5-

nitr

ofur

fury

lide

ne) a

min

o]-

2-ox

azol

idin

one

HC

lN

ithia

zide

z 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

3-( 5

-Nitr

o-2-

fury

l)-i

mid

azo(

12-

a)

pyri

dine

z 4-

( 5-N

itro-

2-fu

ryl)

thia

zole

N

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

ide

NN

-[6-

( 5-N

itro

-2-f

uryl

) -S-

tria

zine

-24

-diy

l] bis

acet

amid

e5-

Nitr

oace

naph

then

ez 1-

[(5-

Nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

itrom

etha

nez

1-N

itrop

yren

eN

orle

stri

nz O

chra

toxi

nA

z N

-(9-

Oxo

-2-

uore

nyl)

acet

amid

ePh

enac

etin

z Ph

enes

teri

nz Ph

IPH

Clz

Proc

arba

zine

HC

lz Pr

opan

esu

lton

e1

2-Pr

opyl

ene

oxid

ez St

yren

ey Su

lfal

late

z 4

4-S

ulfo

nylb

isac

etan

ilid

eTo

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uor

o-N

-[4-

( 5-n

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

idez

Trp

-P-2

acet

atez

Vin

ylch

lori

dez

FD

ampC

viol

etno

1y

Mes

ovar

ium

Rat

2Sa

lbut

amol

Ter

buta

line

Myo

card

ium

Mou

se2

Est

radi

olm

usta

rdy

Phen

este

rinz

Nas

alca

vity

bB

ush

baby

1N

-Nitr

osod

ieth

ylam

ine

Ham

ster

11A

ceta

ldeh

yde

Dia

llyln

itros

amin

eD

imet

hylc

arba

myl

chlo

ride

Hyd

razi

nez

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osom

ethy

l-2

3-di

hydr

oxyp

ropy

lam

ine

N-N

itros

omor

phol

ine

N-N

itros

onor

nico

tine

N-N

itros

opip

erid

inez

Mou

se6

Ally

lgly

cidy

leth

ery

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 1

2-D

ibro

moe

than

ez Fo

rmal

dehy

dez

N-N

itro

sohe

xam

ethy

lene

imin

e1

2-Pr

opyl

ene

oxid

ez

Rat

43A

ceta

ldeh

yde

Acr

ylon

itril

e1-

Azo

xypr

opan

eB

enze

nez

Bis

-(ch

loro

met

hyl)

ethe

rz p-

Cre

sidi

nez

Dia

llyln

itros

amin

e1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dim

ethy

lnitr

amin

eD

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

e1

4-D

ioxa

nez

12-

Epo

xybu

tane

y Z

-Eth

yl-O

NN

-azo

xyet

hane

E

thyl

benz

ene

Eth

ylni

tros

ocya

nam

ide

Form

alde

hyde

z H

exam

ethy

lpho

spho

ram

ide

Hyd

razi

nez

N-N

itro

so-N

-met

hyld

ecyl

amin

edi

( N-N

itro

so) -

perh

ydro

pyri

mid

ine

N-N

itros

o(2

22-

tri

uoro

ethy

l)et

hyla

min

e1-

Nitr

oso-

34

5-tr

imet

hylp

iper

azin

eN

-Nitr

osoa

llyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyle

than

olam

ine

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

dipr

opyl

amin

eN

itros

oeth

ylm

ethy

lam

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nitr

osom

ethy

l-( 2

-hyd

roxy

ethy

l)am

ine

N-N

itro

som

ethy

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

norn

icot

ine-

1-N

-oxi

de

N-N

itro

sopi

peri

dine

z P

hena

cetin

z Ph

enyl

glyc

idyl

ethe

r1

2-Pr

opyl

ene

oxid

ez V

inyl

acet

atez

Vin

ylch

lori

dez

Ner

vous

Mou

se3

13-

But

adie

nez

N-N

itros

odim

ethy

lam

inez

Pro

carb

azin

eH

Clz

syst

emR

at21

Acr

ylam

ide

Acr

ylon

itril

eB

rom

oeth

anez

Chl

oram

buci

lz 1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

eC

yclo

phos

pham

idez

1-E

thyl

-1-n

itros

oure

aE

thyl

eneo

xide

z 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

eaG

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

R(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

S(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

M

ethy

lnit

ram

ine

N-N

itros

o-N

-met

hylu

reaz

N-N

itros

odie

than

olam

ine

1-P

heny

l-3

3-di

met

hyltr

iaze

neP

roca

rbaz

ine

HC

lz P

ropa

nesu

ltone

Vin

ylch

lori

dez

Ora

lcav

ityc

Ham

ster

4A

ceta

ldeh

yde

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itros

omor

phol

ine

N-N

itro

sopi

peri

dine

z

Mou

se3

N-N

itros

ohex

amet

hyle

neim

ine

12

3-T

rich

loro

prop

anez

Vin

ylac

etat

ez

Rat

32A

cryl

amid

eA

cryl

onitr

ile

Ben

zene

z 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

CI

dir

ectb

lue

15C

Id

irec

tblu

e21

8z C

hlor

opre

nez

3-D

iazo

tyra

min

eH

Cl

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

eG

lyci

dolz

IQz

MeA

-a-C

acet

atez

N-N

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

hydr

oxyp

ropy

lam

ine

Nit

roso

-23

-dih

ydro

xypr

opyl

-2-

oxop

ropy

lam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

itro

soam

ylur

etha

nN

-Nitr

osod

ieth

ylam

ine

Nit

roso

ethy

lure

than

N

itros

ohep

tam

ethy

lene

imin

e1-

Nitr

osoh

ydan

toin

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

thia

ldin

eN

-Nitr

osot

hiom

orph

olin

eC

Ia

cid

red

114

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tolu

eney

12

3-T

rich

loro

prop

anez

Xyl

ene

mix

ture

( m-x

ylen

eo-

xyle

nep

-xyl

ene)

Ova

ryM

ouse

10B

enze

nez

13-

But

adie

nez

Die

thyl

stil

best

rolz

N-M

ethy

lola

cryl

amid

ey 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

5-N

itroa

cena

phth

enez

1-[(

5-N

itro

furf

uryl

iden

e)am

ino]

hyda

ntoi

nz P

heno

lpht

hale

inz

Tam

oxif

enci

trat

ez 4-

Vin

ylcy

cloh

exen

ePa

ncre

asH

amst

er3

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

itro

so-2

6-d

imet

hylm

orph

olin

eN

itro

so-2

-oxo

prop

ylet

hano

lam

ine

Mon

key

1U

reth

anez

Rat

222-

Am

ino-

5-ni

trop

heno

ly 1-

( Am

inom

ethy

l)cy

cloh

exan

eace

ticac

idA

zase

rine

But

ylbe

nzyl

phth

alat

ey C

hlor

endi

cac

idz

Cin

nam

ylan

thra

nila

tez

Clo

bra

tey

Dic

hlor

vosz

Eth

ylal

coho

ly H

ydro

chlo

ro

uoro

carb

on12

3IQ

HC

lM

alon

alde

hyde

sod

ium

saltz

MeA

-a-C

acet

atez

2-M

erca

ptob

enzo

thia

zole

y M

ethy

lclo

fena

pate

z N

-(N

-Met

hyl-

N-n

itros

ocar

bam

oyl)

-l-o

rnit

hine

4-(

Met

hyln

itro

sam

ino)

-1-(

3-py

ridy

l)-1

-but

anol

4-(

Met

hyln

itros

amin

o)-1

-( 3

-pyr

idyl

) -1-

( but

anon

e)N

afen

opin

Nitr

ofen

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)z1

23

-Tri

chlo

ropr

opan

ez

Peri

tone

alM

ouse

8B

is-1

2-(

chlo

rom

etho

xy) e

than

eB

is-1

4-(

chlo

rom

etho

xy) -

p-xy

lene

Bis

-(ch

loro

met

hyl)

ethe

rz C

hlor

opre

nez

tran

s-1

4-D

ichl

orob

uten

e-2

cavi

tyD

imet

hylc

arba

myl

chlo

ride

Phe

noxy

benz

amin

eH

Clz

Tri

s-1

23-

( chl

orom

etho

xy) p

ropa

neR

at22

Acr

onyc

ine

Acr

ylam

ide

Act

inom

ycin

DA

nili

neH

Cly

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

rom

ate

pota

ssiu

mz

Chl

oroz

otoc

in

Cyt

embe

nay

Dap

sone

y 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

4-D

ioxa

nez

Eth

ylen

eox

idez

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz M

elph

alan

z N

-Met

hyl-

N4

-din

itros

oani

line

Mit

omyc

in-C

N-N

itro

so-2

24

-tri

met

hyl-

12-

dihy

droq

uino

line

poly

mer

Ph

enox

yben

zam

ine

HC

lz o-

Tolu

idin

eH

Clz

( Con

tinue

don

next

page

)

645

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Pitu

itar

ygl

and

Mou

se8

Die

thyl

stil

best

rolz

Eno

vid

Eth

ylen

eth

iour

eaz

Iodi

nate

dgl

ycer

olz

Isop

rene

Nor

lest

rinz

Pro

pylt

hiou

raci

lz Z

eara

leno

ney

Rat

73-

Am

inot

riaz

olez

12-

Dib

rom

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylal

coho

ly 2-

Mer

capt

oben

zoth

iazo

ley

Met

roni

dazo

lez

Nor

lest

rinz

Pros

tate

Rat

4C

adm

ium

chlo

ride

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

PhIP

HC

lz

Skin

Ham

ster

2U

reth

anez

Vin

ylch

lori

dez

Mou

se5

5-A

zacy

tidin

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Chl

orop

rene

z G

lyci

dolz

Thi

o-te

paz

Rat

332-

Ace

tyla

min

ouo

rene

z 3-

Am

ino-

9-et

hylc

arba

zole

mix

ture

z 1-

Azo

xypr

opan

e2-

Azo

xypr

opan

eB

enze

nez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

ol

tech

nica

lgra

dez

CI

dir

ectb

lue

15C

arbo

xym

ethy

lnitr

osou

rea

24-

Dia

min

oani

sole

sulf

atez

Dib

rom

odul

cito

lz D

ibro

mom

anni

tolz

Dim

etho

xane

2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

Dim

ethy

lvin

ylch

lori

dez

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

26-

dini

trot

olue

ne)z

1-E

thyl

nitr

oso-

3-( 2

-hyd

roxy

ethy

l)-u

rea

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz 1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

IQ

z L

asio

carp

ine

MeI

Qxz

N-(

N-M

ethy

l-N

-nitr

osoc

arba

moy

l)-l

-orn

ithi

ne

5-N

itro-

o-an

isid

inez

CI

aci

dre

d11

4p-

Ros

anili

neH

Clz

Thi

o-te

paz

Thi

oure

ay V

inyl

chlo

ride

z F

Damp

Cvi

olet

no1

y

Smal

lint

esti

neM

ouse

6C

apta

folz

Cap

tanz

N-E

thyl

-N-n

itro

-N-n

itro

sogu

anid

ine

Hyd

roge

npe

roxi

deN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-(

Tri

chlo

rom

ethy

lthi

o)ph

thal

imid

eM

onke

y1

Ure

than

ez

Rat

29A

cryl

onitr

ile

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is( 2

3-d

ibro

mop

ropy

l)ph

osph

ate

mag

nesi

umsa

lt4

-Bis

( 2-h

ydro

xyet

hyl)

amin

o-2-

( 5-n

itro

-2-t

hien

yl) q

uina

zolin

eC

Id

irec

tblu

e15

Car

boxy

met

hyln

itros

oure

a1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

e2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro

-2-f

uryl

)py

rim

idin

etr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-[

2-( 5

-nit

ro-2

-fur

yl) v

inyl

] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

Z-E

thyl

-ON

N-a

zoxy

met

hane

1-E

thyl

-1-n

itros

oure

aFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lu-P

-1z

Glu

-P-2

z IQ

z L

asio

carp

ine

N-M

ethy

l-N

-nitr

o-N

-nitr

osog

uani

dine

z N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez N

-Nitr

oso-

N-i

sobu

tylu

rea

3-N

itro

so-2

-oxa

zoli

dino

neN

itro

soet

hylu

reth

ane

PhI

PH

Clz

Pro

pane

sulto

neQ

uerc

etin

y C

Ia

cid

red

114

Trp

-P-2

acet

atez

Sple

enR

at7

Ani

line

HC

ly A

zobe

nzen

ey p-

Chl

oroa

nili

neH

Clz

Dap

sone

y o-

Nitr

osot

olue

neD

ampC

red

no9

y o-

Tolu

idin

eH

Clz

Stom

ach

Ham

ster

18A

F-2z

14-

Din

itros

o-2

6-di

met

hylp

iper

azin

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z H

ydra

zine

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] a

ceta

mid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

N-N

itro

so-2

3-d

ihyd

roxy

prop

yl-2

-hyd

roxy

prop

ylam

ine

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

-Nitr

oso-

ethy

l-2-

oxop

ropy

lure

aN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

itros

o-5-

met

hylo

xazo

lidon

eN

-Nit

roso

-N-m

ethy

lure

than

N-N

itros

o-1

3-ox

azol

idin

eN

-Nit

roso

-2-p

heny

leth

ylur

ea1

-Nit

roso

-34

5-t

rim

ethy

lpip

eraz

ine

Ure

than

ez V

inyl

chlo

ride

z

Mou

se63

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eA

ciu

orfe

nA

F-2

z 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

tran

s-5-

Am

ino-

3[2-

( 5-n

itro-

2-fu

ryl)

viny

l] -1

24-

oxad

iazo

leA

reco

line

HC

lB

enza

ldeh

ydey

Ben

zofu

ranz

Ben

zotr

ichl

orid

eB

enzy

lace

tate

y B

enzy

lchl

orid

ey B

rom

oeth

anol

13

-But

adie

nez

But

ylat

edhy

drox

yani

sole

z 1

1-di

-N-B

utyl

hydr

azin

eC

affe

icac

idz

Cap

tafo

lz C

arba

zole

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z3

-(C

hlor

omet

hyl)

pyri

dine

HC

lz C

hlor

opre

nez

2-C

hlor

opro

pana

l1-

Chl

orop

rope

neC

ypro

tero

neac

etat

e1

1-D

ially

lhyd

razi

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dic

hlor

vosz

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez D

imet

hylv

inyl

chlo

ride

z D

init

roso

pipe

razi

neE

stra

diol

mus

tard

y E

thyl

acry

late

z Fo

rmic

acid

2-[ 4

-( 5

-nit

ro-2

-fur

yl) -

2-th

iazo

lyl] h

ydra

zide

z G

lyci

dolz

2-H

ydra

zino

-4-(

5-ni

tro-

2-fu

ryl)

thia

zole

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

ICI

1628

46z

IQz

Isop

rene

Lov

asta

tin

MeI

Q1

-Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m3

-(5-

Nitr

o-2-

fury

l)-

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] f

orm

amid

ez N

-Nit

roso

-N

-met

hylu

reaz

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

hexa

met

hyle

neim

ine

N-N

itros

opip

erid

inez

b-P

ropi

olac

tone

z Se

sam

olz

Sty

rene

oxid

ez Te

lone

IIt

echn

ical

grad

ez N

-(T

rich

loro

met

hylth

io) p

htha

limid

e1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uo

ro-N

-[4-

( 5-n

itro

-2-f

uryl

) -2-

thia

zoly

l]ac

etam

idez

Tri

ur

alin

tec

hnic

algr

adey

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylac

etat

ez

Rat

85A

ceto

ne[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zone

1-A

ceto

xysa

frol

ey A

cryl

onitr

ile

1-A

llyl

-1-n

itro

sour

ea2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-ox

adia

zole

2-

Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-4-

( 5-n

itro

-2-f

uryl

) thi

azol

ez 1-

Am

yl-1

-nit

roso

urea

Ari

stol

ochi

cac

id

sodi

umsa

lt( 7

7A

AI

21

AA

II)

Ben

zene

z B

enzo

( a) p

yren

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

BL

-634

1H

Cl

N-n

-But

yl-N

-nitr

osou

rea

But

ylat

edhy

drox

yani

sole

z b

-But

yrol

acto

neC

affe

icac

idz

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z4

-Chl

oro-

o-ph

enyl

ened

iam

inez

Chl

oro

uoro

met

hane

3-

( Chl

orom

ethy

l)py

ridi

neH

Clz

Cip

rob

rate

z C

upfe

rron

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez 2

5-D

imet

hoxy

-4-a

min

osti

lben

ez D

imet

hylh

ydro

gen

phos

phit

ey 4

6-D

imet

hyl-

2-( 5

-nit

ro-2

-fu

ryl)

pyri

mid

ine

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lvin

ylch

lori

dez

Epi

chlo

rohy

drin

y E

thyl

acry

late

z E

thyl

ene

oxid

ez 2-

Flu

oroe

thyl

-nitr

osou

rea

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-

nitr

osou

reaz

1-( 3

-Hyd

roxy

prop

yl) -

1-ni

tros

oure

a1

-Hyd

roxy

safr

olez

ICI

1628

46z

Lox

tidin

eL

upit

idin

e3H

Cl

Mer

curi

cch

lori

dey

3-M

etho

xyca

tech

ol4

-Met

hoxy

phen

olN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-M

ethy

l-N

-nit

roso

benz

amid

e4-

Met

hylc

atec

hol

Met

hyln

itro

socy

anam

ide

3-( 5

-Nit

ro-2

-fur

yl) -

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

4-( 5

-Nit

ro-2

-fur

yl) t

hiaz

ole

2-N

itro

uo

rene

8-N

itro

quin

olin

eN

itro

so-B

aygo

nN

-Nit

roso

-23

-dih

ydro

xypr

opyl

-2-h

ydro

xypr

opyl

amin

eN

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

oxop

ropy

lam

ine

1-N

itro

so-3

5-d

imet

hyl-

4-be

nzoy

lpip

eraz

ine

N-N

itro

so-N

-met

hyl-

N-d

odec

ylam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itro

so-N

-met

hylu

reaz

Nit

roso

-12

36

-tet

rahy

drop

yrid

ine

N-N

itro

sobe

nzth

iazu

ron

Nitr

osod

ibut

ylam

inez

N-N

itros

odie

thyl

amin

eN

-Nit

roso

ephe

drin

eN

itros

oeth

ylur

etha

nO

mep

razo

ley

Phen

acet

inz

Piv

alol

acto

ney

b-P

ropi

olac

tone

z N

-Pro

pyl-

N-n

itro

-N-n

itro

sogu

anid

ine

12-

Pro

pyle

neox

idez

Ses

amol

z St

yren

eox

idez

Sulf

alla

tez

Telo

neII

tec

hnic

algr

adez

12

3-T

rich

loro

prop

anez

24

6-T

rim

ethy

lani

line

HC

lz

646

Subc

utan

eous

Mou

se4

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

2-D

ibro

moe

than

ez N

2-c

-Glu

tam

yl-p

-hyd

razi

nobe

nzoi

cac

idG

lyci

dolz

tissu

eR

at13

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ichl

oroe

than

ez D

imet

hoxa

ne1

4-D

ioxa

nez

MeA

-a-C

acet

atez

44

-Met

hyle

ne-b

is( 2

-met

hyla

nili

ne)

o-N

itro

soto

luen

ep-

Ros

anili

neH

Clz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 2

45-

Tri

met

hyla

nilin

eH

Clz

25-

Xyl

idin

eH

Clz

Test

isM

ouse

4D

ieth

ylst

ilbe

stro

lz Fi

nast

erid

eR

eser

pine

z Ta

mox

ifen

citr

atez

Rat

185-

Aza

cytid

inez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

3-B

utad

iene

z N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

Cad

miu

mch

lori

de

2-C

hlor

o-1

11-

tri

uoro

etha

ne1

1-D

ichl

oro-

1-u

oroe

than

eH

ydro

chlo

rou

oroc

arbo

n12

3M

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z M

etro

nida

zole

z N

-Nit

roso

dim

ethy

lam

inez

Oxo

linic

acid

y SD

Z20

0-11

01

11

2-Te

tra

uoro

etha

ney

Tri

chlo

roet

hyle

nez

Tri

nitr

ogly

ceri

nV

inyl

chlo

ride

z

Thy

roid

glan

dH

amst

er4

Hex

achl

orob

enze

nez

Hyd

razi

nez

Met

hylt

hiou

raci

lU

reth

anez

Mou

se18

3-A

min

o-4-

etho

xyac

etan

ilide

y H

Cbl

ueno

1z

tert

-But

ylal

coho

lz C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

24

-Dia

min

oani

sole

sulf

atez

Die

thyl

stil

best

rolz

Dox

ylam

ine

succ

inat

ez E

thio

nam

idey

Eth

ylen

eth

iour

eaz

44

-Met

hyle

nedi

anil

ine

2HC

lz 1

5-N

apht

hale

nedi

amin

ez N

itrob

enze

nez

Oxa

zepa

my

44

-Oxy

dian

iline

z C

Ip

igm

entr

ed3z

Sulf

amet

hazi

ne2

37

8-T

etra

chlo

rodi

benz

o-p-

diox

inz

44

-Thi

odia

nilin

ez

Rat

33A

cryl

amid

e3-

Am

inot

riaz

olez

o-A

nisi

dine

HC

lz B

emit

radi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

Chl

orop

rene

z 2

4-D

iam

inoa

niso

lesu

lfat

ez N

N-D

ieth

ylth

iour

eay

1-E

thyl

-1-n

itro

sour

ea

Eth

ylen

eth

iour

eaz

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Flu

vast

atin

Gly

cido

lz Io

dina

ted

glyc

erol

z Is

obut

eney

Mal

onal

dehy

des

odiu

msa

ltz

Met

him

azol

e4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Mir

exp

hoto

-N

itro

benz

enez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

44

-Oxy

dian

iline

z Pr

opyl

thio

urac

ilz p-

Ros

anil

ine

HC

lz 2

37

8-Te

trac

hlor

odib

enzo

-p-d

ioxi

nz 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tri

met

hylt

hiou

reay

Vin

ylac

etat

ez Z

inc

dim

ethy

ldith

ioca

rbam

atez

Uri

nary

blad

der

Dog

23

3-D

ichl

orob

enzi

dine

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nilin

e)H

amst

er3

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

acet

amid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

Mou

se12

2-A

cety

lam

ino

uore

nez

4-A

min

odip

heny

l2-

Am

inod

iphe

nyle

neox

ide

o-A

nisi

dine

HC

lz 4-

Chl

oro-

4-a

min

odip

heny

leth

erz

p-C

resi

dine

z 4-

Eth

ylsu

lpho

nyln

apht

hale

ne-1

-sul

fona

mid

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hena

cetin

z Te

lone

IIt

echn

ical

grad

ez U

raci

lz

Mon

key

12-

Nap

hthy

lam

inez

Rat

49A

ceta

min

ophe

nz A

llyli

soth

iocy

anat

ey 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

4-A

min

o-2-

nitr

ophe

noly

11-A

min

ound

ecan

oic

acid

y o-

Ani

sidi

neH

Clz

Ari

stol

ochi

cac

ids

odiu

msa

lt( 7

7A

AI

21

AA

II)

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

ispe

rse

blue

1y N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

4-C

hlor

o-o-

phen

ylen

edia

min

ez m

-Cre

sidi

ney

p-C

resi

dine

z C

yclo

phos

pham

idez

Die

thyl

ene

glyc

olD

imet

hyla

rsin

icac

idy

Fose

tylA

lIQ

HC

lM

eA-a

-Cac

etat

ez M

elam

iney

2-M

etho

xy-3

-am

inod

iben

zofu

ran

2-N

apht

hyla

min

ez N

itril

otri

acet

icac

idz

Nitr

ilot

riac

etic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez o-

Nitr

oani

sole

z N

-Nitr

oso-

N-m

ethy

l-N

-dod

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

l-N

-tet

rade

cyla

min

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itro

sodi

phen

ylam

iney

o-N

itros

otol

uene

N-O

xydi

ethy

lene

thio

carb

amyl

-N-o

xydi

ethy

lene

sulf

enam

ide

Phe

nace

tinz

Phen

azon

eo-

Phen

ylph

enat

eso

dium

y o-

Phen

ylph

enol

y P

otas

sium

bica

rbon

ate

Purp

urin

Que

rcet

iny

p-Q

uino

nedi

oxim

ey Sa

ccha

rin

sodi

umy

Sali

cyla

zosu

lfap

yrid

inez

o-To

luen

esul

fona

mid

eo-

Tolu

idin

eH

Clz

Trp

-P-2

acet

atez

Ura

cilz

Ute

rus

Ham

ster

1N

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aM

ouse

12B

rom

oeth

anez

Chl

oroe

than

ey D

acar

bazi

nez

12-

Dic

hlor

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylen

eox

idez

Gly

cido

lz ( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Proc

arba

zine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez T

rim

ethy

lpho

spha

tey

Vin

ylac

etat

ez

Rat

26A

cryl

amid

e1-

Ally

l-1-

nitr

osou

rea

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

myl

-1-n

itros

oure

aA

traz

iney

CI

dir

ectb

lue

15B

rom

ocri

ptin

em

esyl

atey

N-n

-But

yl-N

-nit

roso

urea

Cal

cium

valp

roat

eC

apta

nz 2-

Chl

oro-

11

1-tr

iuo

roet

hane

Dac

arba

zine

z D

amin

ozid

ez 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

lD

imet

hyla

min

oeth

ylni

tros

oeth

ylur

ean

itri

tesa

lt1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

ICR

F-1

59z

Isop

hosp

ham

idez

15-

Nap

htha

lene

diam

inez

Nit

robe

nzen

ez N

orle

stri

nz 4

4-T

hiod

iani

linez

Vin

ylac

etat

ez

Vag

ina

Mou

se1

AZ

Tz

Rat

2A

ZT

z N

-n-B

utyl

-N-n

itro

sour

ea( C

ontin

ued

onne

xtpa

ge)

647

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Vas

cula

rsy

stem

Ham

ster

91

2-D

imet

hylh

ydra

zine

2H

Cl

Gly

cido

lz H

exac

hlor

oben

zene

z N

-Nit

roso

-eth

yl-2

-oxo

prop

ylur

eaN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

-Nitr

oso-

oxop

ropy

lchl

oroe

thyl

urea

N-N

itro

so-o

xopr

opyl

urea

N-N

itros

o-2-

phen

ylet

hylu

rea

Vin

ylch

lori

dez

Mou

se59

A-a

-CN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-ph

enyl

hydr

azin

eA

llyl

hydr

azin

eH

Cl

Are

colin

eH

Cl

Aza

thio

prin

eB

enzi

dine

2H

Cl

2-B

iphe

nyla

min

eH

Cly

13-

But

adie

nez

Cap

tafo

lz C

arba

myl

hydr

azin

eH

Cl

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 1-

Chl

oro-

4-ni

trob

enze

ney

5-C

hlor

o-o-

tolu

idin

ey 4-

Chl

oro-

o-to

luid

ine

HC

ly p-

Chl

oroa

nilin

eH

Clz

Chl

orop

rene

z C

upfe

rron

z D

acar

bazi

nez

Dam

inoz

idez

24-

Dia

min

otol

uene

2H

Clz

12-

Dib

rom

oeth

anez

Dif

talo

ne7

12-

Dim

ethy

lben

z(a)

anth

race

ne1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylhy

draz

ine

HC

lG

lu-P

-1z

Glu

-P-2

z p-

Hyd

razi

nobe

nzoi

cac

idH

Cl

1-H

ydro

xysa

frol

ez Is

opre

neM

eA-a

-Cac

etat

ez N

-Met

hyl-

N-f

orm

ylhy

draz

ine

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

Mic

hler

rsquoske

tone

z 5-

Nitr

o-o-

tolu

idin

ey N

itro

fenz

N-N

itros

o-N

-met

hylu

reaz

Pent

achl

oroa

niso

lez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y2

34

56

-Pen

tach

loro

phen

olt

echn

ical

grad

ez n-

Pen

tylh

ydra

zine

HC

lPh

enyl

ethy

lhyd

razi

nesu

lfat

ePh

enyl

hydr

azin

eH

Cl

Ster

igm

atoc

ysti

nz Te

tra

uoro

ethy

lene

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)zo

-Tol

uidi

neH

Clz

24

6-T

rich

loro

anil

iney

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nili

neH

Clz

Ure

than

ez V

inyl

carb

amat

eV

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y 2

5-X

ylid

ine

HC

lz

Mon

key

2A

ato

xin

B1y

Ure

than

ez

Rat

32A

nilin

eH

Cly

Azo

benz

eney

Ben

zene

z C

livor

ine

Cup

ferr

onz

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neI

QH

Cl

Las

ioca

rpin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line)

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-N

itros

o-( 2

-hyd

roxy

prop

yl) -

( 2-h

ydro

xyet

hyl)

amin

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nitr

osob

is( 2

-oxo

prop

yl) a

min

eN

-Nit

roso

diet

hano

lam

ine

N-N

itro

sodi

ethy

lam

ine

N-N

itros

odim

ethy

lam

inez

N-N

itros

omet

hyl-

( 2-t

osyl

oxye

thyl

) am

ine

N-N

itros

omor

phol

ine

N-N

itro

sopy

rrol

idin

ez Pe

tasi

teni

neS

teri

gmat

ocys

tinz

Sym

phyt

ine

Tetr

auo

roet

hyle

nez

o-To

luid

ine

HC

lz T

rp-P

-2ac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

aT

here

was

nore

port

edta

rget

site

in1

spec

ies

( rat

sor

mic

e)fo

r5

chem

ical

sw

ithsu

pers

crip

tsb

utth

ech

emic

alw

asev

alua

ted

byth

epu

blis

hed

auth

oras

aca

rcin

ogen

ald

rinz

diel

drin

z N

-nit

roso

pyrr

olid

inez

23

45

6-pe

ntac

hlor

ophe

nol

( Dow

icid

eE

C-7

)ya

ndur

etha

nez

bN

asal

cavi

tyin

clud

estis

sues

ofth

eno

sen

asal

turb

inat

esp

aran

asal

sinu

ses

and

trac

hea

c Ora

lcav

ityin

clud

estis

sues

ofth

em

outh

oro

phar

ynx

phar

ynx

and

lary

nx

Ach

emic

alis

liste

dun

der

each

orga

nev

alua

ted

aspo

sitiv

ein

anex

peri

men

tin

that

spec

ies

byat

leas

t1au

thor

The

refo

rea

chem

ical

may

beli

sted

unde

rse

vera

ltar

geto

rgan

san

dev

ery

chem

ical

liste

din

the

tabl

eis

posi

tive

inat

leas

t1sp

ecie

sIn

orde

rto

com

pare

resu

ltsin

rats

and

mic

esy

mbo

lsfo

llow

chem

ical

ste

sted

inbo

thsp

ecie

sa

zin

dica

tes

that

the

chem

ical

ispo

sitiv

eat

som

esi

tein

both

spec

ies

and

ay

indi

cate

sth

atit

was

test

edin

both

butp

ositi

vein

only

1a

Nth

enu

mbe

rof

chem

ical

sw

ithat

leas

t1po

sitiv

ete

stat

that

site

inth

atsp

ecie

sB

ecau

sem

any

chem

ical

sin

duce

tum

ors

atm

ore

than

1si

tein

agi

ven

spec

ies

man

ych

emic

als

appe

arm

ore

than

once

inth

eta

ble

648

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649

species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters

RESULTS IN RATS AND MICE

For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens

TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database

Chemicals evaluated as carcinogenic in

Rats Mice

All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)

Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2

a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not

b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats

All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical

to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included

The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site

Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 3: Compendium of Chemical Carcinogens by Target Organ - Toxnet

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Adr

enal

glan

dH

amst

er1

Ure

than

ez

Mou

se8

Car

bon

tetr

achl

orid

ez F

uran

z 4

4-M

ethy

lene

dian

iline

2H

Clz

Pen

tach

loro

anis

olez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y

23

45

6-P

enta

chlo

roph

enol

tec

hnic

algr

adez

p-R

osan

ilin

eH

Clz

11

2-T

rich

loro

etha

ney

Rat

16B

rom

oeth

anez

4-C

hlor

o-m

-phe

nyle

nedi

amin

ez C

obal

tsul

fate

hept

ahyd

rate

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

Die

thyl

stilb

estr

olz

Eth

ylal

coho

ly In

dolid

anI

som

azol

e2-

Mer

capt

oben

zoth

iazo

ley

Mir

exz

Pen

tach

loro

anis

olez

Phe

nolp

htha

lein

z 1

2-Pr

opyl

ene

oxid

ez C

Ip

igm

entr

ed3z

Res

erpi

nez

Ret

inol

acet

ate

Bon

eR

at5

Acr

onyc

ine

De

azac

ort

NN

-Dim

ethy

lani

liney

1-( 2

-Hyd

roxy

ethy

l)-1

-nit

roso

urea

z o-

Tolu

idin

eH

Clz

Clit

oral

pre

putia

lM

ouse

11A

ceta

ldeh

yde

met

hylf

orm

ylhy

draz

one

Ben

zene

z 1

3-B

utad

iene

z N

-n-B

utyl

-N-f

orm

ylhy

draz

ine

Dim

ethy

lvin

ylch

lori

dez

N-E

thyl

-N-f

orm

ylhy

draz

ine

glan

dH

exan

alm

ethy

lfor

myl

hydr

azon

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eP

enta

nalm

ethy

lfor

myl

hydr

azon

eN

-N-P

ropy

l-N

-for

myl

hydr

azin

eT

hio-

tepa

z

Rat

21A

cryl

amid

eC

Id

irec

tblu

e15

24

-Dia

min

oani

sole

sulf

atez

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

Glu

-P-1

z G

lu-P

-2z

Gly

cido

lz IQ

z Is

opho

rone

y M

eIQ

xz 2-

Mer

capt

oben

zoth

iazo

ley

Nal

idix

icac

idy

15-

Nap

htha

lene

diam

inez

5-N

itro-

o-a

nisi

dine

z 5-

Nit

roac

enap

hthe

nez

p-N

itro

benz

oic

acid

y 1-

Nitr

opyr

ene

CI

aci

dre

d11

41

23-

Tri

chlo

ropr

opan

ez T

rp-P

-2ac

etat

ez

Ear

Zym

balrsquos

glan

dM

ouse

3B

enze

nez

Chl

orop

rene

z C

upfe

rron

z

Rat

41A

cryl

onit

rile

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

Azo

xym

etha

neB

enze

nez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

irec

tblu

e15

N-n

-But

yl-N

-nitr

osou

rea

Chl

oram

buci

lz C

upfe

rron

z N

-1-D

iace

tam

ido

uore

ne2

4-D

iam

inoa

niso

lesu

lfat

ez 3

3-D

ichl

orob

enzi

dine

25

-Dim

etho

xy-4

-am

inos

tilb

enez

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

N-(

2-Fl

uore

nyl)

-22

2-t

riu

oroa

ceta

mid

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

Hyd

razo

benz

enez

IQz

IQH

Cl

MeI

Qxz

2-M

etho

xy-3

-am

inod

iben

zofu

ran

8-M

etho

xyps

oral

enN

-(N

-Met

hyl-

N-n

itro

soca

rbam

oyl)

-l-o

rnit

hine

44

-Met

hyle

ne-

bis(

2-ch

loro

anili

ne)

5-N

itro-

o-an

isid

inez

5-N

itroa

cena

phth

enez

N-(

9-O

xo-2

-uo

reny

l)ac

etam

ide

Phen

acet

inz

Pre

dnim

usti

neC

Ia

cid

red

114

p-R

osan

iline

HC

lz T

hio-

tepa

z 4

4-T

hiod

iani

line

z b

-Thi

ogua

nine

deox

yrib

osid

e1

23-

Tri

chlo

ropr

opan

ez V

inyl

chlo

ride

z V

inyl

uor

idez

Eso

phag

usH

amst

er2

AF-

2z N

-Nitr

oso-

N-m

ethy

lure

than

eM

ouse

8B

enzo

( a) p

yren

ez 1

2-D

ibro

moe

than

ez N

-Eth

yl-N

-nit

ro-N

-nit

roso

guan

idin

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

3-( 5

-Nit

ro-2

-fur

yl) -

imid

azo(

12-

a) p

yrid

inez

Nitr

osod

ibut

ylam

inez

N-N

itros

ohex

amet

hyle

neim

ine

Vin

ylac

etat

ez

Mon

key

1N

-Nitr

oso-

N-m

ethy

lure

az

Rat

362

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

N-n

-But

yl-N

-nitr

osou

rea

Dih

ydro

safr

olez

Dim

ethy

lvin

ylch

lori

dez

Din

itro

soho

mop

iper

azin

eZ

-Eth

yl-O

NN

-azo

xyet

hane

N-M

ethy

l-N

-nitr

o-N

-nit

roso

guan

idin

ez 3-

( 5-N

itro

-2-f

uryl

) -im

idaz

o(1

2-a

) pyr

idin

ez N

-Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-hy

drox

ypro

pyla

min

eN

itro

so-2

3-d

ihyd

roxy

prop

yl-2

-oxo

prop

ylam

ine

N-N

itro

so-(

2-hy

drox

ypro

pyl)

-(2-

hydr

oxye

thyl

) am

ine

N-N

itros

o-N

-met

hyl-

4-u

oroa

nilin

eN

itros

o-N

-met

hyl-

N-(

2-ph

enyl

) eth

ylam

ine

Nitr

oso-

12

36-

tetr

ahyd

ropy

ridi

neN

-Nit

roso

( 22

2-t

riu

oroe

thyl

) eth

ylam

ine

N-N

itros

oall

yl-2

3-d

ihyd

roxy

prop

ylam

ine

N-N

itro

soal

lyl-

2-hy

drox

ypro

pyla

min

eN

-Nit

roso

ally

l-2-

oxop

ropy

lam

ine

Nitr

osoa

myl

uret

han

Nitr

osoa

naba

sine

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

ipro

pyla

min

eN

itro

soet

hylu

reth

ane

Nit

roso

hept

amet

hyle

neim

ine

N-N

itro

som

ethy

l-2

3-di

hydr

oxyp

ropy

lam

ine

N-N

itros

omet

hyl-

2-hy

drox

ypro

pyla

min

eN

-Nit

roso

met

hyl(

2-ox

opro

pyl)

amin

e2-

Nitr

osom

ethy

lam

inop

yrid

ine

Nit

roso

met

hyla

nili

neN

-Nitr

oson

orni

cotin

e-1-

N-o

xide

N-N

itro

sopi

peri

dine

z N

-Nit

roso

thia

ldin

eN

-Nit

roso

thio

mor

phol

ine

Gal

lbla

dder

Ham

ster

1N

-Met

hyl-

N-f

orm

ylhy

draz

ine

Mou

se4

N-E

thyl

-N-f

orm

ylhy

draz

ine

N-M

ethy

l-N

-for

myl

hydr

azin

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eN

-N-P

ropy

l-N

-for

myl

hydr

azin

eM

onke

y1

Aa

toxi

nB

y 1H

arde

rian

glan

dM

ouse

19B

enze

nez

Ben

zidi

ne2

HC

l2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

13-

But

adie

nez

Cap

tafo

lz C

hlor

opre

nez

Cup

ferr

onz

Dic

hlor

oace

tyle

nez

Eth

ylen

eox

idez

Gen

tian

viol

etG

lyci

dolz

Iodi

nate

dgl

ycer

olz

Isop

rene

N-M

ethy

lola

cryl

amid

ey N

itro

met

hane

z 4

4-O

xydi

anil

inez

12

3-T

rich

loro

prop

anez

24

6-T

rini

tro-

13-

dim

ethy

l-5-

tert

-but

ylbe

nzen

eV

inyl

uor

idez

Hem

atop

oiet

icM

ouse

53A

ceta

mid

ez A

at

oxin

cru

dez

Ally

liso

vale

rate

z tr

ans-

5-A

min

o-3[

2-( 5

-nitr

o-2-

fury

l)vi

nyl] -

12

4-ox

adia

zole

2-A

min

o-4-

( p-n

itro

phen

yl) t

hiaz

ole

syst

em2-

Am

inoa

nthr

aqui

none

z 5-

Aza

cyti

dine

z A

zath

iopr

ine

Ben

zene

z 1

4-B

enzo

quin

one

Ben

zotr

ichl

orid

eB

enzo

ylhy

draz

ine

13-

But

adie

nez

12-

di-n

-But

ylhy

draz

ine

2HC

lC

apta

folz

Chl

oram

buci

lz C

hlor

inat

edpa

raf

ns( C

234

3ch

lori

ne)y

Cyc

loph

osph

amid

ez D

acar

bazi

nez

DD

Tz

Dib

rom

odul

cito

lz D

ibro

mom

anni

tolz

Est

radi

olm

usta

rdy

Eth

ylen

eox

idez

5-Fl

uoro

urac

ily Fo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

entia

nvi

olet

Hex

anam

idey

2-H

ydra

zino

-4-(

p-am

inop

heny

l)th

iazo

lez

2-H

ydra

zino

-4-

( p-n

itro

phen

yl) t

hiaz

olez

1-( 2

-Hyd

roxy

ethy

l)-1

-nit

roso

urea

z IC

RF

-159

z Is

opho

spha

mid

ez Is

opre

neM

eIQ

xz M

elph

alan

z 1-

Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

mM

ethy

lmet

hane

sulf

onat

e4

4-M

ethy

lene

dian

ilin

e2H

Clz

Met

roni

dazo

lez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hene

ster

inz

Phe

nolp

htha

lein

z Ph

IPH

Clz

Phor

bol

Proc

arba

zine

HC

lz S

trob

ane

Tetr

auo

roet

hyle

nez

Thi

o-te

paz

p-To

lylu

reay

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez U

reth

anez

CI

vat

yello

w4y

( Con

tinue

don

next

page

)

641

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Mon

key

1P

roca

rbaz

ine

HC

lz

Rat

56A

llyl

isov

aler

atez

1-A

myl

-1-n

itros

oure

aA

traz

iney

Ben

zidi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

CI

dir

ectb

lue

15

N-n

-But

yl-N

-nitr

osou

rea

Cad

miu

mch

lori

deC

hlor

ambu

cilz

Cyc

loph

osph

amid

ez D

acar

bazi

nez

13-

Dib

utyl

-1-n

itro

sour

eaD

ichl

oroa

cety

lene

z 3

3-D

ichl

orob

enzi

dine

Dic

hlor

vosz

Dim

etho

xane

33

-Dim

etho

xybe

nzid

ine-

44

-dii

socy

anat

ey 3

3-D

imet

hoxy

benz

idin

e2H

Cl

Dim

ethy

lmor

phol

inop

hosp

hora

mid

atey

2-( 2

2-D

imet

hylh

ydra

zino

) -4-

( 5-n

itro-

2-fu

ryl)

thia

zole

Eth

ylen

eox

idez

Form

alde

hyde

z Fo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z F

uran

z G

lyci

dolz

FD

ampC

gree

nno

1y

FDamp

Cgr

een

no2

y H

emat

oxyl

in2

-Hyd

razi

no-4

-(p-

amin

ophe

nyl)

thia

zole

z H

ydro

quin

onez

1-( 2

-Hyd

roxy

ethy

l)-1

-nit

roso

urea

z Io

dina

ted

glyc

erol

z L

asio

carp

ine

2-M

erca

ptob

enzo

thia

zole

y M

etep

aM

ethy

lter

t-bu

tyle

ther

z M

irex

z l-

5-M

orph

olin

omet

hyl-

3-[(

5-ni

trof

urfu

ryli

dene

) am

ino]

-2-o

xazo

lidi

none

H

Cl

Nit

rite

sod

ium

y N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez o-

Nit

roan

isol

ez 1-

[(5-

Nitr

ofur

fury

liden

e)am

ino]

-2-i

mid

azol

idin

one

1-N

itro

pyre

neN

itros

o-N

-met

hyl-

N-(

2-ph

enyl

) eth

ylam

ine

N-N

itros

odie

than

olam

ine

PhIP

HC

lz P

roca

rbaz

ine

HC

lz P

ropa

nesu

ltone

N-P

ropy

l-N

-nit

roso

urea

FD

ampC

red

no2

FD

ampC

red

no4

y Te

trac

hlor

oeth

ylen

ez Te

tra

uoro

ethy

lene

z T

hio-

tepa

z 2

46-

Tri

chlo

roph

enol

z T

rp-P

-2ac

etat

ez

Kid

ney

Ham

ster

1B

rom

ate

pota

ssiu

mz

Mou

se26

o-B

enzy

l-p-

chlo

roph

enol

y 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z B

rom

odic

hlor

omet

hane

z 1

3-B

utad

iene

z 1

2-di

-n-B

utyl

hydr

azin

e2H

Cl

Caf

feic

acid

z C

hlor

ofor

mz

Chl

orop

rene

z D

amin

ozid

ez 2

4-D

iam

inop

heno

l2H

Cly

Dic

hlor

oace

tyle

nez

24-

Din

itrot

olue

ne( c

onta

inin

g1

0-1

52

6-di

nitr

otol

uene

)zH

ydro

quin

onez

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z 3-

Hyd

roxy

-p-b

utyr

ophe

neti

dide

L

ead

acet

ate

basi

cz M

ercu

rym

ethy

lchl

orid

eN

itril

otri

acet

icac

idz

Och

rato

xin

Az

Phe

nace

tinz

CI

pig

men

tred

3z St

rept

ozot

ocin

z T

ris(

2-ch

loro

ethy

l)ph

osph

atez

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez V

inyl

iden

ech

lori

dey

Mon

key

1C

ycas

inan

dm

ethy

lazo

xym

etha

nola

ceta

teR

at86

A

atox

inB

1y 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 1-

Am

ino-

2-m

ethy

lant

hraq

uino

nez

2-A

min

o-5-

( 5-n

itro-

2-fu

ryl)

-13

4-o

xadi

azol

e2-

Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

e2-

Am

ino-

4-ni

trop

heno

ly 2-

Am

ino-

5-ni

trot

hiaz

oley

o-A

nisi

dine

HC

lz A

rist

oloc

hic

acid

so

dium

salt

( 77

AA

I21

A

AII

) A

zoxy

met

hane

Bar

bita

lso

dium

Ben

zofu

ranz

Bro

mat

epo

tass

ium

z B

rom

odic

hlor

omet

hane

z te

rt-B

utyl

alco

holz

Caf

feic

acid

z C

apta

folz

Cap

tanz

Chl

orin

ated

para

fns

( C12

60

chlo

rine

)zC

hlor

ofor

mz

3-( p

-Chl

orop

heny

l)-1

1-d

imet

hylu

reay

Chl

orop

rene

z C

hlor

otha

loni

ly C

inna

myl

anth

rani

late

z C

itrin

inC

oum

arin

z D

ichl

oroa

cety

lene

z 1

4-D

ichl

orob

enze

nez

Die

thyl

acet

amid

e3

4-D

ihyd

roco

umar

inz

Dim

etho

xane

Dim

ethy

lmet

hylp

hosp

hona

tey

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

N-4

-(4

-Flu

orob

iphe

nyl)

acet

amid

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lyci

neH

exac

hlor

obut

adie

ne

Hex

achl

oroe

than

ez H

exam

ethy

lmel

amin

e2-

Hyd

razi

no-4

-(5-

nitr

o-2-

fury

l)th

iazo

lez

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roqu

inon

ez 1-

( 2-H

ydro

xyet

hyl)

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itro

sour

eaz

Isop

horo

ney

Lea

dac

etat

ey L

ead

acet

ate

basi

cz d-

Lim

onen

ey 2-

Met

hoxy

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min

odib

enzo

fura

n8-

Met

hoxy

psor

alen

Z-M

ethy

l-O

NN

-azo

xyet

hane

Met

hylt

ert-

buty

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erz

N-(

N-M

ethy

l-N

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roso

carb

amoy

l)-l

-orn

ithi

nea

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hylb

enzy

lalc

ohol

y M

irex

z l-

5-M

orph

olin

omet

hyl-

3-[(

5-ni

trof

urfu

rylid

ene)

amin

o]-2

-oxa

zolid

inon

eH

Cl

Nit

rilo

tria

ceti

cac

idz

Nit

rilo

tria

cetic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

3-( 5

-Nitr

o-2-

fury

l)-i

mid

azo(

12-

a) p

yrid

inez

N-[

3-( 5

-Nitr

o-2-

fury

l)-1

24

-oxa

diaz

ole-

5-yl

] -m

ethy

l]ac

etam

ide

N-[

5-( 5

-Nitr

o-2-

fury

l)-1

34

-thi

adia

zol-

2-yl

] ace

tam

idez

o-N

itro

anis

olez

Nitr

oben

zene

z 2-

Nit

ro

uore

ne

1-[(

5-N

itrof

urfu

rylid

ene)

amin

o]hy

dant

oinz

1-N

itro

so-1

-hyd

roxy

ethy

l-3-

chlo

roet

hylu

rea

N-N

itro

sodi

etha

nola

min

eN

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roso

diet

hyla

min

eN

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osod

imet

hyla

min

ez N

-Nit

roso

pyrr

olid

inez

Och

rato

xin

Az

CI

aci

dor

ange

3y N

-Oxy

diet

hyle

neth

ioca

rbam

yl-N

-oxy

diet

hyle

nesu

lfen

amid

eP

hena

cetin

z Ph

enaz

one

Phen

olph

thal

einz

Phen

ylbu

tazo

nez

o-Ph

enyl

phen

ate

sodi

umy

Que

rcet

iny

Salic

ylaz

osul

fapy

ridi

nez

Str

epto

zoto

cinz

Tetr

achl

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thyl

enez

Tetr

auo

roet

hyle

nez

Tetr

ahyd

rofu

ranz

12

3-T

rich

loro

prop

anez

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylch

lori

dez

Lar

gein

test

ine

Ham

ster

51

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

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zine

2H

Cl

Hyd

razi

nez

Met

hylh

ydra

zine

Ure

than

ezM

ouse

1C

apsa

icin

Rat

32A

at

oxin

B1y

1-A

llyl

-1-n

itros

oure

a1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z A

myl

opec

tin

sulf

ate

Azo

xym

etha

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

te

chni

calg

rade

z C

Id

irec

tblu

e15

Bro

mod

ichl

orom

etha

nez

N-N

-But

yl-n

-nitr

osou

rea

Car

rage

enan

aci

d-de

grad

edC

hrys

azin

z D

extr

ansu

lfat

eso

dium

( DS-

M-1

) 3

3-D

imet

hoxy

benz

idin

e2H

Cl

33

-Dim

ethy

lben

zidi

ne2

HC

lz Z

-Eth

yl-O

NN

-azo

xym

etha

ne1

-Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

Glu

-P-1

z G

lu-P

-2z

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

IQz

o-N

itro

anis

olez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

Phe

nazo

pyri

dine

HC

lz P

hIP

HC

lz C

Ia

cid

red

114

44

-Thi

odia

nilin

ez T

ribr

omom

etha

ney

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez

Liv

erD

og2

33

-Dic

hlor

oben

zidi

ne4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line

)H

amst

er16

2-A

cety

lam

ino

uore

nez

pp

-DD

Ey

12-

Dim

ethy

lhyd

razi

ne2

HC

lH

exac

hlor

oben

zene

z H

ydra

zine

sulf

atez

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z N

-Met

hyl-

N-f

orm

ylhy

draz

ine

Met

hylh

ydra

zine

Met

hyln

itros

amin

o-N

N-d

imet

hyle

thyl

amin

eN

-Nitr

oso-

13-

oxaz

olid

ine

Nit

roso

-2-o

xopr

opyl

etha

nola

min

eN

-Nitr

osoa

llyl-

2-ox

opro

pyla

min

eN

-Nit

roso

azet

idin

eN

-Nit

roso

mor

phol

ine

N-N

itros

opip

erid

inez

N-N

itros

opyr

rolid

inez

Mou

se23

1A

-a-C

Ace

tam

inop

henz

2-A

cety

lam

ino

uore

nez

Aci

uor

fen

Ald

rinz

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

min

o-2-

met

hyla

nthr

aqui

none

z 2-

Am

inoa

nthr

aqui

none

z 4-

Am

inod

iphe

nyl

2-A

min

odip

heny

lene

oxid

e3-

Am

inot

riaz

olez

Ara

mite

z A

rocl

or12

54y

Aur

amin

e-O

z B

enzi

dine

2H

Cl

Ben

zofu

ranz

Ben

zyla

ceta

tey

3-B

enzy

lsyd

none

-4-a

ceta

mid

ez B

is( 2

-chl

oro-

1-m

ethy

leth

yl) e

ther

tec

hnic

algr

adey

Bis

-2-c

hlor

oeth

ylet

her

Bis

-2-h

ydro

xyet

hyld

ithio

carb

amic

acid

pot

assi

umC

Id

irec

tbla

ck38

CI

dir

ectb

lue

218z

HC

blue

no1

z H

Cbl

ueno

1( p

uri

ed)

Bro

mod

ichl

orom

etha

nez

13-

But

adie

nez

But

ylat

edhy

drox

ytol

uene

y 1

1-di

-n-B

utyl

hydr

azin

eC

apta

folz

Car

bazo

le

Car

bon

tetr

achl

orid

ez C

hlor

alhy

drat

eC

hlor

ambe

ny C

hlor

dane

tec

hnic

algr

adey

Chl

oren

dic

acid

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

1-

Chl

oro-

2-ni

trob

enze

ney

1-C

hlor

o-4-

nitr

oben

zene

y 4-

Chl

oro-

m-p

heny

lene

diam

inez

4-C

hlor

o-o-

phen

ylen

edia

min

ez 5-

Chl

oro-

o-to

luid

iney

642

[ 4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

] ace

ticac

idz

4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

( N-b

-hyd

roxy

ethy

l)ac

etam

idez

Chl

oroa

ceta

ldeh

yde

p-C

hlor

oani

line

HC

lz C

hlor

oben

zila

tey

Chl

orod

ibro

mom

etha

ney

Chl

orof

orm

z C

hlor

opre

nez

Chr

ysaz

inz

CI-

924

Cin

nam

ylan

thra

nila

tez

Cip

ro

brat

ez C

lobu

zari

ty C

ompo

und

LY17

1883

Cou

mar

inz

p-C

resi

dine

z C

upfe

rron

z C

ycla

mat

eso

dium

y C

yclo

chlo

roti

neC

ypro

tero

neac

etat

ep

p-D

DD

y p

p-D

DE

y D

DT

z D

ialla

te2

4-D

iam

inot

olue

nez

24-

Dia

min

otol

uene

2H

Clz

35-

Dic

hlor

o-( N

-11

-dim

ethy

l-2-

prop

ynyl

) ben

zam

ide

26-

Dic

hlor

o-p-

phen

ylen

edia

min

ey D

ichl

oroa

cetic

acid

z 1

4-D

ichl

orob

enze

nez

12-

Dic

hlor

opro

pane

y D

icof

oly

Die

ldri

nz D

ifta

lone

34

-Dih

ydro

coum

arin

z D

ihyd

rosa

frol

ez 2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 1

1-D

imet

hylh

ydra

zine

y 1

4-D

ioxa

nez

55-

Dip

heny

lhyd

anto

iny

Dip

yron

ey D

oxyl

amin

esu

ccin

atez

Est

rago

led

l-E

thio

nine

z o-

Eth

oxyb

enza

mid

eN

-Eth

yl-N

-for

myl

hydr

azin

eE

thyl

ene

imin

eE

thyl

ene

thio

urea

z 2-

Eth

ylhe

xano

ly di

( 2-E

thyl

hexy

l)ad

ipat

ey di

( 2-E

thyl

hexy

l)ph

thal

atez

4-F

luor

o-4-

amin

odip

heny

lF

uran

z Fu

rfur

alz

Gen

tian

viol

etG

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

Gri

seof

ulvi

nH

CD

Dm

ixtu

rez

Hep

tach

lory

Hex

achl

orob

enze

nez

a-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

z b

-12

34

56

-Hex

achl

oroc

yclo

hexa

nec

-12

34

56

-Hex

achl

oroc

yclo

hexa

ney

Hex

achl

oroc

yclo

hexa

ne

tech

nica

lgra

deH

exac

hlor

oeth

anez

Hex

anal

met

hylf

orm

ylhy

draz

one

Hyd

razi

nesu

lfat

ez H

ydra

zobe

nzen

ez H

ydro

quin

onez

N-H

ydro

xy-2

-ac

etyl

amin

ouo

rene

z 1

-Hyd

roxy

estr

agol

e2-

Hyd

roxy

ethy

lhyd

razi

ne1

-Hyd

roxy

safr

olez

IQz

Ison

iazi

dz Is

opre

neK

epon

ez L

eupe

ptin

Lov

asta

tinL

uteo

skyr

inM

alon

alde

hyde

sod

ium

saltz

MeA

-a-C

acet

atez

MeI

QM

eIQ

xz M

ethi

dath

ion

3-M

etho

xy-4

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inoa

zobe

nzen

eM

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z N

-Met

hyl-

N-f

orm

ylhy

draz

ine

3-M

ethy

lbut

anal

met

hylf

orm

ylhy

draz

one

44

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hyle

ne-b

is( 2

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oroa

nili

ne)

2HC

ly M

ethy

lene

chlo

ride

z 4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Met

hylh

ydra

zine

N-M

ethy

lola

cryl

amid

ey M

ethy

lphe

nida

teH

Cly

Mic

hler

rsquoske

tone

z M

irex

z 1

5-N

apht

hale

nedi

amin

ez 2-

Nap

hthy

lam

inez

Nit

hiaz

idez

3-N

itro-

p-ac

etop

hene

tidey

5-N

itro-

o-an

isid

inez

2-N

itro

-p-p

heny

lene

diam

iney

5-N

itro

-o-t

olui

dine

y 5-

Nitr

oace

naph

then

ez o-

Nitr

oani

sole

z N

itrob

enze

nez

6-N

itrob

enzi

mid

azol

ey N

itro

fenz

Nit

rom

etha

nez

Nitr

osod

ibut

ylam

inez

N-N

itros

odim

ethy

lam

inez

p-N

itros

odip

heny

lam

inez

N-N

itro

sohe

xam

ethy

lene

imin

eN

-Nit

roso

pipe

ridi

nez

Non

abro

mob

iphe

nyl

Och

rato

xin

Az

Oxa

zepa

my

44

-Oxy

dian

iline

z Pe

ntac

hlor

oeth

aney

Pent

achl

oron

itrob

enze

ney

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y 2

34

56-

Pen

tach

loro

phen

olt

echn

ical

grad

ez P

enta

nalm

ethy

lfor

myl

hydr

azon

eP

hena

zopy

ridi

neH

Clz

Phe

noba

rbit

aly

Phen

obar

bita

lso

dium

z Ph

enyl

buta

zone

z o-

Phen

ylen

edia

min

e2H

Clz

Pipe

rony

l-bu

toxi

dez

Pipe

rony

lsul

foxi

dey

Poly

brom

inat

edbi

phen

ylm

ixtu

rez

Prob

enec

idy

N-N

-Pro

pyl-

N-f

orm

ylhy

draz

ine

Damp

Cre

dno

5z

Rif

ampi

ciny

Rip

azep

amy

p-R

osan

iline

HC

lz S

afro

lez

Sali

cyla

zosu

lfap

yrid

inez

Sel

eniu

mdi

ethy

ldith

ioca

rbam

ate

Sel

eniu

msu

lde

z S

trob

ane

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

11

12-

Tetr

achl

oroe

than

ey 1

12

2-Te

trac

hlor

oeth

aney

Tetr

achl

oroe

thyl

enez

Tetr

achl

orvi

npho

sy Te

tra

uoro

-m-p

heny

lene

diam

ine

2HC

ly Te

tra

uoro

ethy

lene

z Te

trah

ydro

fura

nz T

hioa

ceta

mid

ez 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

m-T

olui

dine

HC

ly o-

Tolu

idin

eH

Clz

p-To

luid

ine

HC

ly To

xaph

eney

T-2

toxi

nT

riam

tere

ney

Tri

chlo

roac

etic

acid

y 2

46-

Tri

chlo

roan

iline

y 1

12-

Tri

chlo

roet

hane

y T

rich

loro

ethy

lene

z T

rich

loro

ethy

lene

( wit

hout

epic

hlor

ohyd

rin)

y 2

46-

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chlo

roph

enol

z 1

23-

Tri

chlo

ropr

opan

ez T

ri

ural

int

echn

ical

grad

ey 2

45-

Tri

met

hyla

nili

nez

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nilin

eH

Clz

24

6-T

rini

tro-

13-

dim

ethy

l-5-

tert

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ylbe

nzen

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ris(

2-ch

loro

ethy

l)ph

osph

atez

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez T

ris(

2-et

hylh

exyl

) pho

spha

tey

Trp

-P-1

acet

atez

Trp

-P-2

acet

atez

Ure

than

ez V

inyl

carb

amat

eV

inyl

uo

ride

z 2

5-X

ylid

ine

HC

lz C

Id

ispe

rse

yell

ow3z

Zea

rale

none

y

Mon

key

8A

ato

xin

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Cyc

asin

and

met

hyla

zoxy

met

hano

lace

tate

IQ

z N

-Nitr

osod

ieth

ylam

ine

N-N

itro

sodi

prop

ylam

ine

N-N

itro

sopi

peri

dine

z S

teri

gmat

ocys

tinz

Ure

than

ez

Rat

206

Ace

tam

idez

Ace

tam

inop

henz

Ace

toxi

me

2-A

cety

lam

ino

uore

nez

A

atox

icol

A

atox

inB

y 1A

at

oxin

cru

dez

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

min

o-2-

met

hyla

nthr

aqui

none

z 2-

Am

inoa

nthr

aqui

none

z o-

Am

inoa

zoto

luen

ey 11

-Am

inou

ndec

anoi

cac

idy

Ara

mit

ez A

rocl

or12

60A

uram

ine-

Oz

Azo

xym

etha

neB

emit

radi

ne

Ben

zidi

ne3

-Ben

zyls

ydno

ne-4

-ace

tam

idez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

CI

dir

ectb

lue

15

Bro

mod

ichl

orom

etha

nez

Bud

eson

ide

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Chl

oren

dic

acid

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 2-

Chl

oro-

5-( 3

5-d

imet

hylp

iper

idin

osul

phon

yl) b

enzo

icac

id[

4-C

hlor

o-6-

( 23

-xy

lidi

no) -

2-py

rim

idin

ylth

io] a

ceti

cac

idz

4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

( N-b

-hyd

roxy

ethy

l)ac

etam

idez

Chl

orob

enze

ney

Chl

orof

orm

z 3-

( p-C

hlor

ophe

nyl)

-11

-dim

ethy

lure

ay C

ipro

bra

tez

Cliv

orin

eC

lob

rate

y C

loph

enA

30C

oum

arin

z p-

Cre

sidi

nez

Cro

tona

ldeh

yde

Cup

ferr

onz

Cyc

lope

ntan

one

oxim

eD

DT

z D

ecab

rom

odip

heny

loxi

dey

Deh

ydro

epia

ndro

ster

one

Deh

ydro

epia

ndro

ster

one

acet

ate

24-

Dia

min

otol

uene

z 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ibro

moe

than

ez D

ichl

oroa

ceti

cac

idz

Dic

hlor

oace

tyle

nez

NN

-Die

thyl

-4-(

4-[

pyri

dyl-

1-o

xide

] azo

) ani

line

Die

thyl

stil

best

rolz

Dim

etho

xane

3

3-D

imet

hoxy

benz

idin

e2H

Cl

56-

Dim

etho

xyst

erig

mat

ocys

tinN

N-D

imet

hyl-

4-am

inoa

zobe

nzen

e6-

Dim

ethy

lam

ino-

44-

diph

enyl

-3-h

epta

nola

ceta

teH

Cly

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hyln

itram

ine

Din

itros

ohom

opip

eraz

ine

26-

Din

itro

tolu

ene

24-

Din

itrot

olue

ne( c

onta

inin

g1

0-1

52

6-di

nitr

otol

uene

)z

Din

itrot

olue

net

echn

ical

grad

e( 2

4( 7

7) -

and

26

( 19

) -)

14-

Dio

xane

z D

ipen

tyln

itro

sam

ine

Dox

ylam

ine

succ

inat

ez E

thin

yles

trad

iol

Eth

ioni

ne

dl-E

thio

nine

z 4-

Eth

oxy-

phen

ylur

eaE

thyl

alco

holy

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neE

thyl

ene

thio

urea

z di

( 2-E

thyl

hexy

l)ph

thal

atez

Flu

cona

zole

y N

-(2-

Flu

oren

yl) -

22

2-tr

iuo

roac

etam

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

Fum

onis

inB

1F

uran

z Fu

rfur

alz

Glu

-P-1

z G

lu-P

-2z

FDamp

Cgr

een

no1

y H

CD

Dm

ixtu

rez

Hex

achl

orob

enze

nez

a-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

z H

ydra

zine

z H

ydra

zine

sulf

atez

Hyd

razo

benz

enez

Hyd

roch

loro

uor

ocar

bon

123

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z 1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-nitr

oso-

3-ch

loro

ethy

lure

a1

-Hyd

roxy

safr

olez

IQz

IQH

Cl

Ison

iazi

dz K

epon

ez L

asio

carp

ine

MeA

-a-C

acet

atez

MeI

Qxz

Met

hapy

rile

neH

Cl

Z-M

ethy

l-O

NN

-azo

xyet

hane

Met

hylc

arba

mat

ey M

ethy

lclo

fena

pate

z 3

-Met

hyl-

4-di

met

hyla

min

oazo

benz

ene

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

4-( 4

-N-M

ethy

l-N

-nit

rosa

min

osty

ryl)

quin

olin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line

) 4

4-M

ethy

lene

dian

ilin

e2H

Clz

4-( M

ethy

lnit

rosa

min

o)-1

-(3-

pyri

dyl)

-1-(

buta

none

) M

etro

nida

zole

z M

ichl

errsquos

keto

nez

Mir

exz

Mon

ocro

tali

neN

afen

opin

Nit

rite

sod

ium

y N

itrob

enze

nez

2-N

itro

buta

ne2

-Nit

ro

uore

ne3

-Nit

rope

ntan

eN

-Nitr

oso-

bis-

( 44

4-t

ri

uoro

-N-b

utyl

) am

ine

1-N

itros

o-5

6-di

hydr

oura

cil

N-N

itro

so-2

3-d

ihyd

roxy

prop

ylet

hano

lam

ine

1-N

itros

o-1-

hydr

oxye

thyl

-3-c

hlor

oeth

ylur

ea1

-Nitr

oso-

1-( 2

-hyd

roxy

prop

yl) -

3-ch

loro

ethy

lure

aN

-Nitr

oso-

( 2-h

ydro

xypr

opyl

) -( 2

-hyd

roxy

ethy

l)am

ine

N-N

itros

o-N

-met

hyl-

N-d

odec

ylam

ine

Nit

roso

-N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

e

( Con

tinue

don

next

page

)

643

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

N-N

itro

so-N

-met

hyld

ecyl

amin

e3-

Nit

roso

-2-o

xazo

lidin

one

Nit

roso

-2-o

xopr

opyl

etha

nola

min

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osoa

llyl

etha

nola

min

eN

-Nit

roso

bis(

2-ox

opro

pyl)

amin

eN

itro

sodi

buty

lam

inez

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

imet

hyla

min

ez p-

Nitr

osod

iphe

nyla

min

ez N

-Nit

roso

dipr

opyl

amin

eN

itros

odod

ecam

ethy

lene

imin

eN

-Nit

roso

ephe

drin

eN

itro

soet

hylm

ethy

lam

ine

Nitr

osoh

epta

met

hyle

neim

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

met

hyl-

( 2-h

ydro

xyet

hyl)

amin

eN

-Nitr

osom

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

-Nitr

osom

ethy

l(2-

oxop

ropy

l)am

ine

N-N

itro

som

ethy

l-( 2

-tos

ylox

yeth

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eN

-Nit

roso

mor

phol

ine

N-N

itros

opip

erid

inez

N-N

itro

sopy

rrol

idin

ez N

-Nit

roso

thia

ldin

eo-

Nit

roso

tolu

ene

Nor

lest

rinz

N-(

9-O

xo-2

-uo

reny

l)ac

etam

ide

44

-Oxy

dian

iline

z 2

34

56-

Pent

achl

orop

heno

lte

chni

calg

rade

z P

etas

iten

ine

Phe

noba

rbit

als

odiu

mz

1-P

heny

lazo

-2-n

apht

holy

o-P

heny

lene

diam

ine

2HC

lz P

iper

onyl

buto

xide

z P

olyb

rom

inat

edbi

phen

ylm

ixtu

rez

Pre

dnis

olon

eP

yril

amin

em

alea

tey

CI

aci

dre

d11

4C

Ip

igm

entr

ed3z

Damp

Cre

dno

5z

Damp

Cre

dno

9y

FD

ampC

red

no1

p-

Ros

anili

neH

Clz

Saf

role

z Se

leni

umsu

lde

z Se

nkir

kine

Ste

rigm

atoc

ystin

z S

ymph

ytin

eTa

mox

ifen

citr

atez

Telo

neII

tec

hnic

algr

adez

33

44

-Te

traa

min

obip

heny

l4H

Clz

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

auo

roet

hyle

nez

Thi

oace

tam

idez

44

-Thi

odia

nilin

ez To

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

Tri

amci

nolo

neac

eton

ide

24

5-T

rim

ethy

lani

line

z 2

45-

Tri

met

hyla

nili

neH

Clz

24

6-T

rim

ethy

lani

line

HC

lz T

rini

trog

lyce

rin

Trp

-P-1

acet

atez

Trp

-P-2

acet

atez

Vin

ylac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

CI

dis

pers

eye

llow

3z

Tre

esh

rew

1A

ato

xin

B1y

Lun

gH

amst

er3

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

1-N

itro

so-3

45

-tri

met

hylp

iper

azin

eM

ouse

116

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-is

onic

otin

oylh

ydra

zine

A

llyl

hydr

azin

eH

Cl

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

Are

coli

neH

Cl

5-A

zacy

tidi

nez

Ben

zene

z B

enzo

fura

nz B

enzo

tric

hlor

ide

Ben

zoyl

hydr

azin

eB

enzy

lhyd

razi

ne2

HC

l2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 2-c

hlor

o-1-

met

hyle

thyl

) eth

er

tech

nica

lgra

dey

Bis

-(ch

loro

met

hyl)

ethe

rz 1

3-B

utad

iene

z N

-n-B

utyl

-N-f

orm

ylhy

draz

ine

But

ylat

edhy

drox

ytol

uene

y 1

1-di

-n-B

utyl

hydr

azin

en-

But

ylhy

draz

ine

HC

l1

2-di

-N-B

utyl

hydr

azin

e2H

Cl

Caf

feic

acid

z C

arba

myl

hydr

azin

eH

Cl

1-C

arba

myl

-2-p

heny

lhyd

razi

neC

hlor

ambu

cilz

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z C

oum

arin

z C

yclo

phos

pham

idez

Dac

arba

zine

z D

amin

ozid

ez p

p-D

DD

y D

DT

z 1

1-D

iall

ylhy

draz

ine

12-

Dia

llyl

hydr

azin

e2H

Cl

Dib

enz(

ah)

anth

race

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

Dib

rom

odul

cito

lz 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

12-

Dic

hlor

oeth

anez

12-

Dif

orm

ylhy

draz

ine

Dih

ydro

safr

olez

25-

Dim

etho

xy-4

-am

inos

tilbe

nez

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

a-E

cdys

one

Est

radi

olm

usta

rdy

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylen

eim

ine

Eth

ylen

eox

idez

Eth

ylhy

draz

ine

HC

l5-

Flu

orou

raci

ly Fo

rmyl

hydr

azin

eG

lyci

dolz

c-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

y H

exan

alm

ethy

lfor

myl

hydr

azon

eH

ydra

zine

z H

ydra

zine

sulf

atez

IQz

Isob

utyl

nitr

itez

Ison

iazi

dz Is

onic

otin

icac

idva

nilly

liden

ehyd

razi

de

Isop

rene

Lov

asta

tinM

eIQ

xz M

elph

alan

z 1-

Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m

N-M

ethy

l-N

-for

myl

hydr

azin

eM

ethy

lmet

hane

sulf

onat

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eM

ethy

lene

chlo

ride

z M

ethy

lhyd

razi

ne

Met

hylh

ydra

zine

sulf

ate

( N-6

) -( M

ethy

lnit

roso

) ade

nine

(N

-6) -

( Met

hyln

itro

so) a

deno

sine

N-M

ethy

lola

cryl

amid

ey M

etro

nida

zole

z M

olyb

denu

mtr

ioxi

dey

Mon

oace

tylh

ydra

zine

Nap

htha

lene

15

-Nap

htha

lene

diam

inez

Nic

otin

icac

idhy

draz

ide

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez 3-

Nitr

o-3-

hexe

nez

Nit

robe

nzen

ez N

itrom

etha

nez

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

dim

ethy

lam

inez

N-N

itros

ohex

amet

hyle

neim

ine

N-N

itro

sopi

peri

dine

z O

zone

y Pe

ntan

alm

ethy

lfor

myl

hydr

azon

en-

Pen

tylh

ydra

zine

HC

lPh

enes

teri

nz Ph

enyl

ethy

lhyd

razi

nesu

lfat

eP

roca

rbaz

ine

HC

lz N

-N-P

ropy

l-N

-for

myl

hydr

azin

eP

ropy

lhyd

razi

neH

Cl

Sel

eniu

msu

lde

z S

trep

tozo

toci

nz Su

lfal

late

z Te

lone

IIt

echn

ical

grad

ez 3

34

4-T

etra

amin

obip

heny

l4H

Clz

Tetr

anitr

omet

hane

z T-

2to

xin

Tri

chlo

roet

hyle

nez

Tri

ura

lint

echn

ical

grad

ey 2

45-

Tri

met

hyla

nilin

eH

Clz

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez U

reth

anez

Vin

ylch

lori

dez

Vin

ylu

orid

ez V

inyl

iden

ech

lori

dey

24-

Xyl

idin

eH

Cly

Mon

key

1U

reth

anez

Rat

551-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro

-2-f

uryl

) -1

34-

oxad

iazo

le2

-Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-5-

nitr

othi

azol

ey 1-

Am

yl-1

-nitr

osou

rea

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is-(

chlo

rom

ethy

l)et

herz

HC

blue

no1

z B

rom

oeth

anez

N-n

-But

yl-N

-nit

roso

urea

Cad

miu

mch

lori

deC

adm

ium

sulp

hate

( 11

) 1-

Chl

oroe

thyl

nitr

oso-

3-( 2

-hyd

roxy

prop

yl) u

rea

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z 1

2-D

ibro

moe

than

ez D

imet

hylh

ydro

gen

phos

phit

ey tr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-

[ 2-(

5-ni

tro-

2-fu

ryl)

viny

l] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

12-

Epo

xybu

tane

y 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

Hyd

razi

nez

Hyd

razi

nesu

lfat

ez 1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

Isob

utyl

nitr

itez

Ison

iazi

dz 4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4-

( Met

hyln

itros

amin

o)-1

-(3-

pyri

dyl)

-1-b

utan

ol4

-(M

ethy

lnit

rosa

min

o)-1

-(3-

pyri

dyl)

-1-(

buta

none

) N

-[ 3

-(5-

Nitr

o-2-

fury

l)-

12

4-ox

adia

zole

-5-y

l] -m

ethy

lace

tam

ide

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

3-N

itro-

3-he

xene

z 5-

Nitr

oace

naph

then

ez N

-Nit

roso

-bis

-(4

44-

tri

uoro

-N-b

utyl

) am

ine

N-N

itros

o-N

-met

hyl-

N-d

odec

ylam

ine

N-N

itros

o-N

-met

hyl-

N-t

etra

decy

lam

ine

N-N

itro

so-N

-met

hyld

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

lure

az N

-Nitr

osob

is( 2

-hyd

roxy

prop

yl)

amin

eN

-Nitr

osob

is-2

3-d

ihyd

roxy

prop

ylam

ine

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itros

odim

ethy

lam

inez

N-N

itro

soep

hedr

ine

Nitr

osoe

thyl

met

hyla

min

eN

-Nit

roso

met

hyl

N-N

itro

som

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eC

Ia

cid

red

114

Sod

ium

dich

rom

ate

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

anit

rom

etha

nez

24

5-T

rim

ethy

lani

line

z 2

46-

Tri

met

hyla

nili

neH

Clz

Vin

ylch

lori

dez

Mam

mar

ygl

and

Dog

1Ly

nest

reno

lH

amst

er1

Vin

ylch

lori

dez

Mou

se24

5-A

zacy

tidin

ez B

enze

nez

CI

dir

ectb

lack

381

3-B

utad

iene

z C

alci

fero

lC

hlor

opre

nez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Die

thyl

stilb

estr

olz

a-E

cdys

one

Est

radi

olE

thyl

ene

oxid

ez F

uros

emid

ey G

lyci

dolz

Gri

seof

ulvi

nIs

onia

zidz

Ison

icot

inic

acid

vani

llylid

eneh

ydra

zide

( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Nitr

oben

zene

z R

eser

pine

z Su

lfal

late

z V

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y

644

Rat

102

4-A

cety

lam

inob

iphe

nyl

2-A

cety

lam

ino

uore

nez

Acr

onyc

ine

Acr

ylam

ide

Acr

ylon

itri

leA

F-2

z 1-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro-

2-fu

ryl)

-13

4-

oxad

iazo

le2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

e2-

Am

ino-

5-ni

trot

hiaz

oley

4-A

min

odip

heny

lHC

l1-

Am

yl-1

-nit

roso

urea

Atr

azin

ey B

emit

radi

ne

Ben

zidi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

4-B

is( 2

-hyd

roxy

ethy

l)am

ino-

2-( 5

-nit

ro-2

-thi

enyl

) qui

nazo

line

13-

But

adie

nez

N-n

-But

yl-N

-nitr

osou

rea

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Car

boxy

met

hyln

itros

oure

aC

hlor

ambu

cilz

Chl

orop

rene

z C

ytem

bena

y D

acar

bazi

nez

N-1

-Dia

ceta

mid

ouo

rene

46

-Dia

min

o-2-

( 5-n

itro-

2-fu

ryl)

-S-t

riaz

ine

24-

Dia

min

oani

sole

sulf

atez

24-

Dia

min

otol

uene

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dib

rom

oman

nito

lz 1

3-D

ibut

yl-1

-nit

roso

urea

33

-Dic

hlor

oben

zidi

ne1

2-D

ichl

oroe

than

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

12-

Dim

ethy

l-5-

nitr

oim

idaz

ole

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lam

inoe

thyl

nitr

osoe

thyl

urea

nitr

ite

salt

33

-Dim

ethy

lben

zidi

ne2

HC

lz 2-

( 22

-Dim

ethy

lhyd

razi

no) -

4-( 5

-nitr

o-2-

fury

l)th

iazo

le

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

24-

Dio

xane

z 1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

6-di

nitr

otol

uene

)zN

-(2-

Fluo

reny

l)-2

22

-tri

uo

roac

etam

ide

Form

icac

id2-

( 4-m

ethy

l-2-

thia

zoly

l)hy

draz

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-

thia

zoly

l] hyd

razi

dez

Gly

cido

lz H

exam

ethy

lmel

amin

eN

-Hex

ylni

tros

oure

a2-

Hyd

razi

no-4

-(p-

amin

ophe

nyl)

thia

zole

z 2-

Hyd

razi

no-4

-( 5

-nit

ro-2

-fur

yl) t

hiaz

olez

2-H

ydra

zino

-4-(

p-ni

trop

heny

l)th

iazo

lez

Hyd

razo

benz

enez

1-( 2

-Hyd

roxy

ethy

l)-3

-[( 5

-nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

e1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

1-(

2-H

ydro

xyet

hyl)

-1-n

itros

oure

az In

dom

etha

cin

IQz

IQH

Cl

Ison

iazi

dz 2-

Met

hoxy

-3-a

min

odib

enzo

fura

n4-

Met

hyl-

1-[(

5-ni

trof

urfu

rylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

-(N

-Met

hyl-

N-n

itro

soca

rbam

oyl)

-l-o

rnit

hine

3-M

ethy

lcho

lant

hren

e4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line)

Met

hyle

nech

lori

dez

Met

roni

dazo

lez

l-5-

Mor

phol

inom

ethy

l-3-

[(5-

nitr

ofur

fury

lide

ne) a

min

o]-

2-ox

azol

idin

one

HC

lN

ithia

zide

z 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

3-( 5

-Nitr

o-2-

fury

l)-i

mid

azo(

12-

a)

pyri

dine

z 4-

( 5-N

itro-

2-fu

ryl)

thia

zole

N

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

ide

NN

-[6-

( 5-N

itro

-2-f

uryl

) -S-

tria

zine

-24

-diy

l] bis

acet

amid

e5-

Nitr

oace

naph

then

ez 1-

[(5-

Nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

itrom

etha

nez

1-N

itrop

yren

eN

orle

stri

nz O

chra

toxi

nA

z N

-(9-

Oxo

-2-

uore

nyl)

acet

amid

ePh

enac

etin

z Ph

enes

teri

nz Ph

IPH

Clz

Proc

arba

zine

HC

lz Pr

opan

esu

lton

e1

2-Pr

opyl

ene

oxid

ez St

yren

ey Su

lfal

late

z 4

4-S

ulfo

nylb

isac

etan

ilid

eTo

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uor

o-N

-[4-

( 5-n

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

idez

Trp

-P-2

acet

atez

Vin

ylch

lori

dez

FD

ampC

viol

etno

1y

Mes

ovar

ium

Rat

2Sa

lbut

amol

Ter

buta

line

Myo

card

ium

Mou

se2

Est

radi

olm

usta

rdy

Phen

este

rinz

Nas

alca

vity

bB

ush

baby

1N

-Nitr

osod

ieth

ylam

ine

Ham

ster

11A

ceta

ldeh

yde

Dia

llyln

itros

amin

eD

imet

hylc

arba

myl

chlo

ride

Hyd

razi

nez

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osom

ethy

l-2

3-di

hydr

oxyp

ropy

lam

ine

N-N

itros

omor

phol

ine

N-N

itros

onor

nico

tine

N-N

itros

opip

erid

inez

Mou

se6

Ally

lgly

cidy

leth

ery

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 1

2-D

ibro

moe

than

ez Fo

rmal

dehy

dez

N-N

itro

sohe

xam

ethy

lene

imin

e1

2-Pr

opyl

ene

oxid

ez

Rat

43A

ceta

ldeh

yde

Acr

ylon

itril

e1-

Azo

xypr

opan

eB

enze

nez

Bis

-(ch

loro

met

hyl)

ethe

rz p-

Cre

sidi

nez

Dia

llyln

itros

amin

e1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dim

ethy

lnitr

amin

eD

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

e1

4-D

ioxa

nez

12-

Epo

xybu

tane

y Z

-Eth

yl-O

NN

-azo

xyet

hane

E

thyl

benz

ene

Eth

ylni

tros

ocya

nam

ide

Form

alde

hyde

z H

exam

ethy

lpho

spho

ram

ide

Hyd

razi

nez

N-N

itro

so-N

-met

hyld

ecyl

amin

edi

( N-N

itro

so) -

perh

ydro

pyri

mid

ine

N-N

itros

o(2

22-

tri

uoro

ethy

l)et

hyla

min

e1-

Nitr

oso-

34

5-tr

imet

hylp

iper

azin

eN

-Nitr

osoa

llyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyle

than

olam

ine

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

dipr

opyl

amin

eN

itros

oeth

ylm

ethy

lam

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nitr

osom

ethy

l-( 2

-hyd

roxy

ethy

l)am

ine

N-N

itro

som

ethy

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

norn

icot

ine-

1-N

-oxi

de

N-N

itro

sopi

peri

dine

z P

hena

cetin

z Ph

enyl

glyc

idyl

ethe

r1

2-Pr

opyl

ene

oxid

ez V

inyl

acet

atez

Vin

ylch

lori

dez

Ner

vous

Mou

se3

13-

But

adie

nez

N-N

itros

odim

ethy

lam

inez

Pro

carb

azin

eH

Clz

syst

emR

at21

Acr

ylam

ide

Acr

ylon

itril

eB

rom

oeth

anez

Chl

oram

buci

lz 1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

eC

yclo

phos

pham

idez

1-E

thyl

-1-n

itros

oure

aE

thyl

eneo

xide

z 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

eaG

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

R(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

S(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

M

ethy

lnit

ram

ine

N-N

itros

o-N

-met

hylu

reaz

N-N

itros

odie

than

olam

ine

1-P

heny

l-3

3-di

met

hyltr

iaze

neP

roca

rbaz

ine

HC

lz P

ropa

nesu

ltone

Vin

ylch

lori

dez

Ora

lcav

ityc

Ham

ster

4A

ceta

ldeh

yde

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itros

omor

phol

ine

N-N

itro

sopi

peri

dine

z

Mou

se3

N-N

itros

ohex

amet

hyle

neim

ine

12

3-T

rich

loro

prop

anez

Vin

ylac

etat

ez

Rat

32A

cryl

amid

eA

cryl

onitr

ile

Ben

zene

z 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

CI

dir

ectb

lue

15C

Id

irec

tblu

e21

8z C

hlor

opre

nez

3-D

iazo

tyra

min

eH

Cl

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

eG

lyci

dolz

IQz

MeA

-a-C

acet

atez

N-N

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

hydr

oxyp

ropy

lam

ine

Nit

roso

-23

-dih

ydro

xypr

opyl

-2-

oxop

ropy

lam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

itro

soam

ylur

etha

nN

-Nitr

osod

ieth

ylam

ine

Nit

roso

ethy

lure

than

N

itros

ohep

tam

ethy

lene

imin

e1-

Nitr

osoh

ydan

toin

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

thia

ldin

eN

-Nitr

osot

hiom

orph

olin

eC

Ia

cid

red

114

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tolu

eney

12

3-T

rich

loro

prop

anez

Xyl

ene

mix

ture

( m-x

ylen

eo-

xyle

nep

-xyl

ene)

Ova

ryM

ouse

10B

enze

nez

13-

But

adie

nez

Die

thyl

stil

best

rolz

N-M

ethy

lola

cryl

amid

ey 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

5-N

itroa

cena

phth

enez

1-[(

5-N

itro

furf

uryl

iden

e)am

ino]

hyda

ntoi

nz P

heno

lpht

hale

inz

Tam

oxif

enci

trat

ez 4-

Vin

ylcy

cloh

exen

ePa

ncre

asH

amst

er3

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

itro

so-2

6-d

imet

hylm

orph

olin

eN

itro

so-2

-oxo

prop

ylet

hano

lam

ine

Mon

key

1U

reth

anez

Rat

222-

Am

ino-

5-ni

trop

heno

ly 1-

( Am

inom

ethy

l)cy

cloh

exan

eace

ticac

idA

zase

rine

But

ylbe

nzyl

phth

alat

ey C

hlor

endi

cac

idz

Cin

nam

ylan

thra

nila

tez

Clo

bra

tey

Dic

hlor

vosz

Eth

ylal

coho

ly H

ydro

chlo

ro

uoro

carb

on12

3IQ

HC

lM

alon

alde

hyde

sod

ium

saltz

MeA

-a-C

acet

atez

2-M

erca

ptob

enzo

thia

zole

y M

ethy

lclo

fena

pate

z N

-(N

-Met

hyl-

N-n

itros

ocar

bam

oyl)

-l-o

rnit

hine

4-(

Met

hyln

itro

sam

ino)

-1-(

3-py

ridy

l)-1

-but

anol

4-(

Met

hyln

itros

amin

o)-1

-( 3

-pyr

idyl

) -1-

( but

anon

e)N

afen

opin

Nitr

ofen

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)z1

23

-Tri

chlo

ropr

opan

ez

Peri

tone

alM

ouse

8B

is-1

2-(

chlo

rom

etho

xy) e

than

eB

is-1

4-(

chlo

rom

etho

xy) -

p-xy

lene

Bis

-(ch

loro

met

hyl)

ethe

rz C

hlor

opre

nez

tran

s-1

4-D

ichl

orob

uten

e-2

cavi

tyD

imet

hylc

arba

myl

chlo

ride

Phe

noxy

benz

amin

eH

Clz

Tri

s-1

23-

( chl

orom

etho

xy) p

ropa

neR

at22

Acr

onyc

ine

Acr

ylam

ide

Act

inom

ycin

DA

nili

neH

Cly

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

rom

ate

pota

ssiu

mz

Chl

oroz

otoc

in

Cyt

embe

nay

Dap

sone

y 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

4-D

ioxa

nez

Eth

ylen

eox

idez

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz M

elph

alan

z N

-Met

hyl-

N4

-din

itros

oani

line

Mit

omyc

in-C

N-N

itro

so-2

24

-tri

met

hyl-

12-

dihy

droq

uino

line

poly

mer

Ph

enox

yben

zam

ine

HC

lz o-

Tolu

idin

eH

Clz

( Con

tinue

don

next

page

)

645

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Pitu

itar

ygl

and

Mou

se8

Die

thyl

stil

best

rolz

Eno

vid

Eth

ylen

eth

iour

eaz

Iodi

nate

dgl

ycer

olz

Isop

rene

Nor

lest

rinz

Pro

pylt

hiou

raci

lz Z

eara

leno

ney

Rat

73-

Am

inot

riaz

olez

12-

Dib

rom

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylal

coho

ly 2-

Mer

capt

oben

zoth

iazo

ley

Met

roni

dazo

lez

Nor

lest

rinz

Pros

tate

Rat

4C

adm

ium

chlo

ride

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

PhIP

HC

lz

Skin

Ham

ster

2U

reth

anez

Vin

ylch

lori

dez

Mou

se5

5-A

zacy

tidin

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Chl

orop

rene

z G

lyci

dolz

Thi

o-te

paz

Rat

332-

Ace

tyla

min

ouo

rene

z 3-

Am

ino-

9-et

hylc

arba

zole

mix

ture

z 1-

Azo

xypr

opan

e2-

Azo

xypr

opan

eB

enze

nez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

ol

tech

nica

lgra

dez

CI

dir

ectb

lue

15C

arbo

xym

ethy

lnitr

osou

rea

24-

Dia

min

oani

sole

sulf

atez

Dib

rom

odul

cito

lz D

ibro

mom

anni

tolz

Dim

etho

xane

2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

Dim

ethy

lvin

ylch

lori

dez

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

26-

dini

trot

olue

ne)z

1-E

thyl

nitr

oso-

3-( 2

-hyd

roxy

ethy

l)-u

rea

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz 1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

IQ

z L

asio

carp

ine

MeI

Qxz

N-(

N-M

ethy

l-N

-nitr

osoc

arba

moy

l)-l

-orn

ithi

ne

5-N

itro-

o-an

isid

inez

CI

aci

dre

d11

4p-

Ros

anili

neH

Clz

Thi

o-te

paz

Thi

oure

ay V

inyl

chlo

ride

z F

Damp

Cvi

olet

no1

y

Smal

lint

esti

neM

ouse

6C

apta

folz

Cap

tanz

N-E

thyl

-N-n

itro

-N-n

itro

sogu

anid

ine

Hyd

roge

npe

roxi

deN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-(

Tri

chlo

rom

ethy

lthi

o)ph

thal

imid

eM

onke

y1

Ure

than

ez

Rat

29A

cryl

onitr

ile

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is( 2

3-d

ibro

mop

ropy

l)ph

osph

ate

mag

nesi

umsa

lt4

-Bis

( 2-h

ydro

xyet

hyl)

amin

o-2-

( 5-n

itro

-2-t

hien

yl) q

uina

zolin

eC

Id

irec

tblu

e15

Car

boxy

met

hyln

itros

oure

a1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

e2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro

-2-f

uryl

)py

rim

idin

etr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-[

2-( 5

-nit

ro-2

-fur

yl) v

inyl

] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

Z-E

thyl

-ON

N-a

zoxy

met

hane

1-E

thyl

-1-n

itros

oure

aFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lu-P

-1z

Glu

-P-2

z IQ

z L

asio

carp

ine

N-M

ethy

l-N

-nitr

o-N

-nitr

osog

uani

dine

z N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez N

-Nitr

oso-

N-i

sobu

tylu

rea

3-N

itro

so-2

-oxa

zoli

dino

neN

itro

soet

hylu

reth

ane

PhI

PH

Clz

Pro

pane

sulto

neQ

uerc

etin

y C

Ia

cid

red

114

Trp

-P-2

acet

atez

Sple

enR

at7

Ani

line

HC

ly A

zobe

nzen

ey p-

Chl

oroa

nili

neH

Clz

Dap

sone

y o-

Nitr

osot

olue

neD

ampC

red

no9

y o-

Tolu

idin

eH

Clz

Stom

ach

Ham

ster

18A

F-2z

14-

Din

itros

o-2

6-di

met

hylp

iper

azin

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z H

ydra

zine

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] a

ceta

mid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

N-N

itro

so-2

3-d

ihyd

roxy

prop

yl-2

-hyd

roxy

prop

ylam

ine

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

-Nitr

oso-

ethy

l-2-

oxop

ropy

lure

aN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

itros

o-5-

met

hylo

xazo

lidon

eN

-Nit

roso

-N-m

ethy

lure

than

N-N

itros

o-1

3-ox

azol

idin

eN

-Nit

roso

-2-p

heny

leth

ylur

ea1

-Nit

roso

-34

5-t

rim

ethy

lpip

eraz

ine

Ure

than

ez V

inyl

chlo

ride

z

Mou

se63

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eA

ciu

orfe

nA

F-2

z 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

tran

s-5-

Am

ino-

3[2-

( 5-n

itro-

2-fu

ryl)

viny

l] -1

24-

oxad

iazo

leA

reco

line

HC

lB

enza

ldeh

ydey

Ben

zofu

ranz

Ben

zotr

ichl

orid

eB

enzy

lace

tate

y B

enzy

lchl

orid

ey B

rom

oeth

anol

13

-But

adie

nez

But

ylat

edhy

drox

yani

sole

z 1

1-di

-N-B

utyl

hydr

azin

eC

affe

icac

idz

Cap

tafo

lz C

arba

zole

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z3

-(C

hlor

omet

hyl)

pyri

dine

HC

lz C

hlor

opre

nez

2-C

hlor

opro

pana

l1-

Chl

orop

rope

neC

ypro

tero

neac

etat

e1

1-D

ially

lhyd

razi

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dic

hlor

vosz

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez D

imet

hylv

inyl

chlo

ride

z D

init

roso

pipe

razi

neE

stra

diol

mus

tard

y E

thyl

acry

late

z Fo

rmic

acid

2-[ 4

-( 5

-nit

ro-2

-fur

yl) -

2-th

iazo

lyl] h

ydra

zide

z G

lyci

dolz

2-H

ydra

zino

-4-(

5-ni

tro-

2-fu

ryl)

thia

zole

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

ICI

1628

46z

IQz

Isop

rene

Lov

asta

tin

MeI

Q1

-Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m3

-(5-

Nitr

o-2-

fury

l)-

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] f

orm

amid

ez N

-Nit

roso

-N

-met

hylu

reaz

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

hexa

met

hyle

neim

ine

N-N

itros

opip

erid

inez

b-P

ropi

olac

tone

z Se

sam

olz

Sty

rene

oxid

ez Te

lone

IIt

echn

ical

grad

ez N

-(T

rich

loro

met

hylth

io) p

htha

limid

e1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uo

ro-N

-[4-

( 5-n

itro

-2-f

uryl

) -2-

thia

zoly

l]ac

etam

idez

Tri

ur

alin

tec

hnic

algr

adey

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylac

etat

ez

Rat

85A

ceto

ne[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zone

1-A

ceto

xysa

frol

ey A

cryl

onitr

ile

1-A

llyl

-1-n

itro

sour

ea2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-ox

adia

zole

2-

Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-4-

( 5-n

itro

-2-f

uryl

) thi

azol

ez 1-

Am

yl-1

-nit

roso

urea

Ari

stol

ochi

cac

id

sodi

umsa

lt( 7

7A

AI

21

AA

II)

Ben

zene

z B

enzo

( a) p

yren

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

BL

-634

1H

Cl

N-n

-But

yl-N

-nitr

osou

rea

But

ylat

edhy

drox

yani

sole

z b

-But

yrol

acto

neC

affe

icac

idz

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z4

-Chl

oro-

o-ph

enyl

ened

iam

inez

Chl

oro

uoro

met

hane

3-

( Chl

orom

ethy

l)py

ridi

neH

Clz

Cip

rob

rate

z C

upfe

rron

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez 2

5-D

imet

hoxy

-4-a

min

osti

lben

ez D

imet

hylh

ydro

gen

phos

phit

ey 4

6-D

imet

hyl-

2-( 5

-nit

ro-2

-fu

ryl)

pyri

mid

ine

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lvin

ylch

lori

dez

Epi

chlo

rohy

drin

y E

thyl

acry

late

z E

thyl

ene

oxid

ez 2-

Flu

oroe

thyl

-nitr

osou

rea

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-

nitr

osou

reaz

1-( 3

-Hyd

roxy

prop

yl) -

1-ni

tros

oure

a1

-Hyd

roxy

safr

olez

ICI

1628

46z

Lox

tidin

eL

upit

idin

e3H

Cl

Mer

curi

cch

lori

dey

3-M

etho

xyca

tech

ol4

-Met

hoxy

phen

olN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-M

ethy

l-N

-nit

roso

benz

amid

e4-

Met

hylc

atec

hol

Met

hyln

itro

socy

anam

ide

3-( 5

-Nit

ro-2

-fur

yl) -

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

4-( 5

-Nit

ro-2

-fur

yl) t

hiaz

ole

2-N

itro

uo

rene

8-N

itro

quin

olin

eN

itro

so-B

aygo

nN

-Nit

roso

-23

-dih

ydro

xypr

opyl

-2-h

ydro

xypr

opyl

amin

eN

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

oxop

ropy

lam

ine

1-N

itro

so-3

5-d

imet

hyl-

4-be

nzoy

lpip

eraz

ine

N-N

itro

so-N

-met

hyl-

N-d

odec

ylam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itro

so-N

-met

hylu

reaz

Nit

roso

-12

36

-tet

rahy

drop

yrid

ine

N-N

itro

sobe

nzth

iazu

ron

Nitr

osod

ibut

ylam

inez

N-N

itros

odie

thyl

amin

eN

-Nit

roso

ephe

drin

eN

itros

oeth

ylur

etha

nO

mep

razo

ley

Phen

acet

inz

Piv

alol

acto

ney

b-P

ropi

olac

tone

z N

-Pro

pyl-

N-n

itro

-N-n

itro

sogu

anid

ine

12-

Pro

pyle

neox

idez

Ses

amol

z St

yren

eox

idez

Sulf

alla

tez

Telo

neII

tec

hnic

algr

adez

12

3-T

rich

loro

prop

anez

24

6-T

rim

ethy

lani

line

HC

lz

646

Subc

utan

eous

Mou

se4

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

2-D

ibro

moe

than

ez N

2-c

-Glu

tam

yl-p

-hyd

razi

nobe

nzoi

cac

idG

lyci

dolz

tissu

eR

at13

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ichl

oroe

than

ez D

imet

hoxa

ne1

4-D

ioxa

nez

MeA

-a-C

acet

atez

44

-Met

hyle

ne-b

is( 2

-met

hyla

nili

ne)

o-N

itro

soto

luen

ep-

Ros

anili

neH

Clz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 2

45-

Tri

met

hyla

nilin

eH

Clz

25-

Xyl

idin

eH

Clz

Test

isM

ouse

4D

ieth

ylst

ilbe

stro

lz Fi

nast

erid

eR

eser

pine

z Ta

mox

ifen

citr

atez

Rat

185-

Aza

cytid

inez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

3-B

utad

iene

z N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

Cad

miu

mch

lori

de

2-C

hlor

o-1

11-

tri

uoro

etha

ne1

1-D

ichl

oro-

1-u

oroe

than

eH

ydro

chlo

rou

oroc

arbo

n12

3M

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z M

etro

nida

zole

z N

-Nit

roso

dim

ethy

lam

inez

Oxo

linic

acid

y SD

Z20

0-11

01

11

2-Te

tra

uoro

etha

ney

Tri

chlo

roet

hyle

nez

Tri

nitr

ogly

ceri

nV

inyl

chlo

ride

z

Thy

roid

glan

dH

amst

er4

Hex

achl

orob

enze

nez

Hyd

razi

nez

Met

hylt

hiou

raci

lU

reth

anez

Mou

se18

3-A

min

o-4-

etho

xyac

etan

ilide

y H

Cbl

ueno

1z

tert

-But

ylal

coho

lz C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

24

-Dia

min

oani

sole

sulf

atez

Die

thyl

stil

best

rolz

Dox

ylam

ine

succ

inat

ez E

thio

nam

idey

Eth

ylen

eth

iour

eaz

44

-Met

hyle

nedi

anil

ine

2HC

lz 1

5-N

apht

hale

nedi

amin

ez N

itrob

enze

nez

Oxa

zepa

my

44

-Oxy

dian

iline

z C

Ip

igm

entr

ed3z

Sulf

amet

hazi

ne2

37

8-T

etra

chlo

rodi

benz

o-p-

diox

inz

44

-Thi

odia

nilin

ez

Rat

33A

cryl

amid

e3-

Am

inot

riaz

olez

o-A

nisi

dine

HC

lz B

emit

radi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

Chl

orop

rene

z 2

4-D

iam

inoa

niso

lesu

lfat

ez N

N-D

ieth

ylth

iour

eay

1-E

thyl

-1-n

itro

sour

ea

Eth

ylen

eth

iour

eaz

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Flu

vast

atin

Gly

cido

lz Io

dina

ted

glyc

erol

z Is

obut

eney

Mal

onal

dehy

des

odiu

msa

ltz

Met

him

azol

e4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Mir

exp

hoto

-N

itro

benz

enez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

44

-Oxy

dian

iline

z Pr

opyl

thio

urac

ilz p-

Ros

anil

ine

HC

lz 2

37

8-Te

trac

hlor

odib

enzo

-p-d

ioxi

nz 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tri

met

hylt

hiou

reay

Vin

ylac

etat

ez Z

inc

dim

ethy

ldith

ioca

rbam

atez

Uri

nary

blad

der

Dog

23

3-D

ichl

orob

enzi

dine

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nilin

e)H

amst

er3

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

acet

amid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

Mou

se12

2-A

cety

lam

ino

uore

nez

4-A

min

odip

heny

l2-

Am

inod

iphe

nyle

neox

ide

o-A

nisi

dine

HC

lz 4-

Chl

oro-

4-a

min

odip

heny

leth

erz

p-C

resi

dine

z 4-

Eth

ylsu

lpho

nyln

apht

hale

ne-1

-sul

fona

mid

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hena

cetin

z Te

lone

IIt

echn

ical

grad

ez U

raci

lz

Mon

key

12-

Nap

hthy

lam

inez

Rat

49A

ceta

min

ophe

nz A

llyli

soth

iocy

anat

ey 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

4-A

min

o-2-

nitr

ophe

noly

11-A

min

ound

ecan

oic

acid

y o-

Ani

sidi

neH

Clz

Ari

stol

ochi

cac

ids

odiu

msa

lt( 7

7A

AI

21

AA

II)

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

ispe

rse

blue

1y N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

4-C

hlor

o-o-

phen

ylen

edia

min

ez m

-Cre

sidi

ney

p-C

resi

dine

z C

yclo

phos

pham

idez

Die

thyl

ene

glyc

olD

imet

hyla

rsin

icac

idy

Fose

tylA

lIQ

HC

lM

eA-a

-Cac

etat

ez M

elam

iney

2-M

etho

xy-3

-am

inod

iben

zofu

ran

2-N

apht

hyla

min

ez N

itril

otri

acet

icac

idz

Nitr

ilot

riac

etic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez o-

Nitr

oani

sole

z N

-Nitr

oso-

N-m

ethy

l-N

-dod

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

l-N

-tet

rade

cyla

min

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itro

sodi

phen

ylam

iney

o-N

itros

otol

uene

N-O

xydi

ethy

lene

thio

carb

amyl

-N-o

xydi

ethy

lene

sulf

enam

ide

Phe

nace

tinz

Phen

azon

eo-

Phen

ylph

enat

eso

dium

y o-

Phen

ylph

enol

y P

otas

sium

bica

rbon

ate

Purp

urin

Que

rcet

iny

p-Q

uino

nedi

oxim

ey Sa

ccha

rin

sodi

umy

Sali

cyla

zosu

lfap

yrid

inez

o-To

luen

esul

fona

mid

eo-

Tolu

idin

eH

Clz

Trp

-P-2

acet

atez

Ura

cilz

Ute

rus

Ham

ster

1N

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aM

ouse

12B

rom

oeth

anez

Chl

oroe

than

ey D

acar

bazi

nez

12-

Dic

hlor

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylen

eox

idez

Gly

cido

lz ( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Proc

arba

zine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez T

rim

ethy

lpho

spha

tey

Vin

ylac

etat

ez

Rat

26A

cryl

amid

e1-

Ally

l-1-

nitr

osou

rea

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

myl

-1-n

itros

oure

aA

traz

iney

CI

dir

ectb

lue

15B

rom

ocri

ptin

em

esyl

atey

N-n

-But

yl-N

-nit

roso

urea

Cal

cium

valp

roat

eC

apta

nz 2-

Chl

oro-

11

1-tr

iuo

roet

hane

Dac

arba

zine

z D

amin

ozid

ez 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

lD

imet

hyla

min

oeth

ylni

tros

oeth

ylur

ean

itri

tesa

lt1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

ICR

F-1

59z

Isop

hosp

ham

idez

15-

Nap

htha

lene

diam

inez

Nit

robe

nzen

ez N

orle

stri

nz 4

4-T

hiod

iani

linez

Vin

ylac

etat

ez

Vag

ina

Mou

se1

AZ

Tz

Rat

2A

ZT

z N

-n-B

utyl

-N-n

itro

sour

ea( C

ontin

ued

onne

xtpa

ge)

647

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Vas

cula

rsy

stem

Ham

ster

91

2-D

imet

hylh

ydra

zine

2H

Cl

Gly

cido

lz H

exac

hlor

oben

zene

z N

-Nit

roso

-eth

yl-2

-oxo

prop

ylur

eaN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

-Nitr

oso-

oxop

ropy

lchl

oroe

thyl

urea

N-N

itro

so-o

xopr

opyl

urea

N-N

itros

o-2-

phen

ylet

hylu

rea

Vin

ylch

lori

dez

Mou

se59

A-a

-CN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-ph

enyl

hydr

azin

eA

llyl

hydr

azin

eH

Cl

Are

colin

eH

Cl

Aza

thio

prin

eB

enzi

dine

2H

Cl

2-B

iphe

nyla

min

eH

Cly

13-

But

adie

nez

Cap

tafo

lz C

arba

myl

hydr

azin

eH

Cl

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 1-

Chl

oro-

4-ni

trob

enze

ney

5-C

hlor

o-o-

tolu

idin

ey 4-

Chl

oro-

o-to

luid

ine

HC

ly p-

Chl

oroa

nilin

eH

Clz

Chl

orop

rene

z C

upfe

rron

z D

acar

bazi

nez

Dam

inoz

idez

24-

Dia

min

otol

uene

2H

Clz

12-

Dib

rom

oeth

anez

Dif

talo

ne7

12-

Dim

ethy

lben

z(a)

anth

race

ne1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylhy

draz

ine

HC

lG

lu-P

-1z

Glu

-P-2

z p-

Hyd

razi

nobe

nzoi

cac

idH

Cl

1-H

ydro

xysa

frol

ez Is

opre

neM

eA-a

-Cac

etat

ez N

-Met

hyl-

N-f

orm

ylhy

draz

ine

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

Mic

hler

rsquoske

tone

z 5-

Nitr

o-o-

tolu

idin

ey N

itro

fenz

N-N

itros

o-N

-met

hylu

reaz

Pent

achl

oroa

niso

lez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y2

34

56

-Pen

tach

loro

phen

olt

echn

ical

grad

ez n-

Pen

tylh

ydra

zine

HC

lPh

enyl

ethy

lhyd

razi

nesu

lfat

ePh

enyl

hydr

azin

eH

Cl

Ster

igm

atoc

ysti

nz Te

tra

uoro

ethy

lene

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)zo

-Tol

uidi

neH

Clz

24

6-T

rich

loro

anil

iney

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nili

neH

Clz

Ure

than

ez V

inyl

carb

amat

eV

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y 2

5-X

ylid

ine

HC

lz

Mon

key

2A

ato

xin

B1y

Ure

than

ez

Rat

32A

nilin

eH

Cly

Azo

benz

eney

Ben

zene

z C

livor

ine

Cup

ferr

onz

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neI

QH

Cl

Las

ioca

rpin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line)

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-N

itros

o-( 2

-hyd

roxy

prop

yl) -

( 2-h

ydro

xyet

hyl)

amin

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nitr

osob

is( 2

-oxo

prop

yl) a

min

eN

-Nit

roso

diet

hano

lam

ine

N-N

itro

sodi

ethy

lam

ine

N-N

itros

odim

ethy

lam

inez

N-N

itros

omet

hyl-

( 2-t

osyl

oxye

thyl

) am

ine

N-N

itros

omor

phol

ine

N-N

itro

sopy

rrol

idin

ez Pe

tasi

teni

neS

teri

gmat

ocys

tinz

Sym

phyt

ine

Tetr

auo

roet

hyle

nez

o-To

luid

ine

HC

lz T

rp-P

-2ac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

aT

here

was

nore

port

edta

rget

site

in1

spec

ies

( rat

sor

mic

e)fo

r5

chem

ical

sw

ithsu

pers

crip

tsb

utth

ech

emic

alw

asev

alua

ted

byth

epu

blis

hed

auth

oras

aca

rcin

ogen

ald

rinz

diel

drin

z N

-nit

roso

pyrr

olid

inez

23

45

6-pe

ntac

hlor

ophe

nol

( Dow

icid

eE

C-7

)ya

ndur

etha

nez

bN

asal

cavi

tyin

clud

estis

sues

ofth

eno

sen

asal

turb

inat

esp

aran

asal

sinu

ses

and

trac

hea

c Ora

lcav

ityin

clud

estis

sues

ofth

em

outh

oro

phar

ynx

phar

ynx

and

lary

nx

Ach

emic

alis

liste

dun

der

each

orga

nev

alua

ted

aspo

sitiv

ein

anex

peri

men

tin

that

spec

ies

byat

leas

t1au

thor

The

refo

rea

chem

ical

may

beli

sted

unde

rse

vera

ltar

geto

rgan

san

dev

ery

chem

ical

liste

din

the

tabl

eis

posi

tive

inat

leas

t1sp

ecie

sIn

orde

rto

com

pare

resu

ltsin

rats

and

mic

esy

mbo

lsfo

llow

chem

ical

ste

sted

inbo

thsp

ecie

sa

zin

dica

tes

that

the

chem

ical

ispo

sitiv

eat

som

esi

tein

both

spec

ies

and

ay

indi

cate

sth

atit

was

test

edin

both

butp

ositi

vein

only

1a

Nth

enu

mbe

rof

chem

ical

sw

ithat

leas

t1po

sitiv

ete

stat

that

site

inth

atsp

ecie

sB

ecau

sem

any

chem

ical

sin

duce

tum

ors

atm

ore

than

1si

tein

agi

ven

spec

ies

man

ych

emic

als

appe

arm

ore

than

once

inth

eta

ble

648

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649

species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters

RESULTS IN RATS AND MICE

For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens

TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database

Chemicals evaluated as carcinogenic in

Rats Mice

All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)

Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2

a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not

b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats

All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical

to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included

The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site

Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 4: Compendium of Chemical Carcinogens by Target Organ - Toxnet

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Mon

key

1P

roca

rbaz

ine

HC

lz

Rat

56A

llyl

isov

aler

atez

1-A

myl

-1-n

itros

oure

aA

traz

iney

Ben

zidi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

CI

dir

ectb

lue

15

N-n

-But

yl-N

-nitr

osou

rea

Cad

miu

mch

lori

deC

hlor

ambu

cilz

Cyc

loph

osph

amid

ez D

acar

bazi

nez

13-

Dib

utyl

-1-n

itro

sour

eaD

ichl

oroa

cety

lene

z 3

3-D

ichl

orob

enzi

dine

Dic

hlor

vosz

Dim

etho

xane

33

-Dim

etho

xybe

nzid

ine-

44

-dii

socy

anat

ey 3

3-D

imet

hoxy

benz

idin

e2H

Cl

Dim

ethy

lmor

phol

inop

hosp

hora

mid

atey

2-( 2

2-D

imet

hylh

ydra

zino

) -4-

( 5-n

itro-

2-fu

ryl)

thia

zole

Eth

ylen

eox

idez

Form

alde

hyde

z Fo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z F

uran

z G

lyci

dolz

FD

ampC

gree

nno

1y

FDamp

Cgr

een

no2

y H

emat

oxyl

in2

-Hyd

razi

no-4

-(p-

amin

ophe

nyl)

thia

zole

z H

ydro

quin

onez

1-( 2

-Hyd

roxy

ethy

l)-1

-nit

roso

urea

z Io

dina

ted

glyc

erol

z L

asio

carp

ine

2-M

erca

ptob

enzo

thia

zole

y M

etep

aM

ethy

lter

t-bu

tyle

ther

z M

irex

z l-

5-M

orph

olin

omet

hyl-

3-[(

5-ni

trof

urfu

ryli

dene

) am

ino]

-2-o

xazo

lidi

none

H

Cl

Nit

rite

sod

ium

y N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez o-

Nit

roan

isol

ez 1-

[(5-

Nitr

ofur

fury

liden

e)am

ino]

-2-i

mid

azol

idin

one

1-N

itro

pyre

neN

itros

o-N

-met

hyl-

N-(

2-ph

enyl

) eth

ylam

ine

N-N

itros

odie

than

olam

ine

PhIP

HC

lz P

roca

rbaz

ine

HC

lz P

ropa

nesu

ltone

N-P

ropy

l-N

-nit

roso

urea

FD

ampC

red

no2

FD

ampC

red

no4

y Te

trac

hlor

oeth

ylen

ez Te

tra

uoro

ethy

lene

z T

hio-

tepa

z 2

46-

Tri

chlo

roph

enol

z T

rp-P

-2ac

etat

ez

Kid

ney

Ham

ster

1B

rom

ate

pota

ssiu

mz

Mou

se26

o-B

enzy

l-p-

chlo

roph

enol

y 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z B

rom

odic

hlor

omet

hane

z 1

3-B

utad

iene

z 1

2-di

-n-B

utyl

hydr

azin

e2H

Cl

Caf

feic

acid

z C

hlor

ofor

mz

Chl

orop

rene

z D

amin

ozid

ez 2

4-D

iam

inop

heno

l2H

Cly

Dic

hlor

oace

tyle

nez

24-

Din

itrot

olue

ne( c

onta

inin

g1

0-1

52

6-di

nitr

otol

uene

)zH

ydro

quin

onez

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z 3-

Hyd

roxy

-p-b

utyr

ophe

neti

dide

L

ead

acet

ate

basi

cz M

ercu

rym

ethy

lchl

orid

eN

itril

otri

acet

icac

idz

Och

rato

xin

Az

Phe

nace

tinz

CI

pig

men

tred

3z St

rept

ozot

ocin

z T

ris(

2-ch

loro

ethy

l)ph

osph

atez

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez V

inyl

iden

ech

lori

dey

Mon

key

1C

ycas

inan

dm

ethy

lazo

xym

etha

nola

ceta

teR

at86

A

atox

inB

1y 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 1-

Am

ino-

2-m

ethy

lant

hraq

uino

nez

2-A

min

o-5-

( 5-n

itro-

2-fu

ryl)

-13

4-o

xadi

azol

e2-

Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

e2-

Am

ino-

4-ni

trop

heno

ly 2-

Am

ino-

5-ni

trot

hiaz

oley

o-A

nisi

dine

HC

lz A

rist

oloc

hic

acid

so

dium

salt

( 77

AA

I21

A

AII

) A

zoxy

met

hane

Bar

bita

lso

dium

Ben

zofu

ranz

Bro

mat

epo

tass

ium

z B

rom

odic

hlor

omet

hane

z te

rt-B

utyl

alco

holz

Caf

feic

acid

z C

apta

folz

Cap

tanz

Chl

orin

ated

para

fns

( C12

60

chlo

rine

)zC

hlor

ofor

mz

3-( p

-Chl

orop

heny

l)-1

1-d

imet

hylu

reay

Chl

orop

rene

z C

hlor

otha

loni

ly C

inna

myl

anth

rani

late

z C

itrin

inC

oum

arin

z D

ichl

oroa

cety

lene

z 1

4-D

ichl

orob

enze

nez

Die

thyl

acet

amid

e3

4-D

ihyd

roco

umar

inz

Dim

etho

xane

Dim

ethy

lmet

hylp

hosp

hona

tey

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

N-4

-(4

-Flu

orob

iphe

nyl)

acet

amid

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lyci

neH

exac

hlor

obut

adie

ne

Hex

achl

oroe

than

ez H

exam

ethy

lmel

amin

e2-

Hyd

razi

no-4

-(5-

nitr

o-2-

fury

l)th

iazo

lez

Hyd

roqu

inon

ez 1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

Isop

horo

ney

Lea

dac

etat

ey L

ead

acet

ate

basi

cz d-

Lim

onen

ey 2-

Met

hoxy

-3-a

min

odib

enzo

fura

n8-

Met

hoxy

psor

alen

Z-M

ethy

l-O

NN

-azo

xyet

hane

Met

hylt

ert-

buty

leth

erz

N-(

N-M

ethy

l-N

-nit

roso

carb

amoy

l)-l

-orn

ithi

nea

-Met

hylb

enzy

lalc

ohol

y M

irex

z l-

5-M

orph

olin

omet

hyl-

3-[(

5-ni

trof

urfu

rylid

ene)

amin

o]-2

-oxa

zolid

inon

eH

Cl

Nit

rilo

tria

ceti

cac

idz

Nit

rilo

tria

cetic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

3-( 5

-Nitr

o-2-

fury

l)-i

mid

azo(

12-

a) p

yrid

inez

N-[

3-( 5

-Nitr

o-2-

fury

l)-1

24

-oxa

diaz

ole-

5-yl

] -m

ethy

l]ac

etam

ide

N-[

5-( 5

-Nitr

o-2-

fury

l)-1

34

-thi

adia

zol-

2-yl

] ace

tam

idez

o-N

itro

anis

olez

Nitr

oben

zene

z 2-

Nit

ro

uore

ne

1-[(

5-N

itrof

urfu

rylid

ene)

amin

o]hy

dant

oinz

1-N

itro

so-1

-hyd

roxy

ethy

l-3-

chlo

roet

hylu

rea

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

imet

hyla

min

ez N

-Nit

roso

pyrr

olid

inez

Och

rato

xin

Az

CI

aci

dor

ange

3y N

-Oxy

diet

hyle

neth

ioca

rbam

yl-N

-oxy

diet

hyle

nesu

lfen

amid

eP

hena

cetin

z Ph

enaz

one

Phen

olph

thal

einz

Phen

ylbu

tazo

nez

o-Ph

enyl

phen

ate

sodi

umy

Que

rcet

iny

Salic

ylaz

osul

fapy

ridi

nez

Str

epto

zoto

cinz

Tetr

achl

oroe

thyl

enez

Tetr

auo

roet

hyle

nez

Tetr

ahyd

rofu

ranz

12

3-T

rich

loro

prop

anez

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylch

lori

dez

Lar

gein

test

ine

Ham

ster

51

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

Hyd

razi

nez

Met

hylh

ydra

zine

Ure

than

ezM

ouse

1C

apsa

icin

Rat

32A

at

oxin

B1y

1-A

llyl

-1-n

itros

oure

a1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z A

myl

opec

tin

sulf

ate

Azo

xym

etha

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

te

chni

calg

rade

z C

Id

irec

tblu

e15

Bro

mod

ichl

orom

etha

nez

N-N

-But

yl-n

-nitr

osou

rea

Car

rage

enan

aci

d-de

grad

edC

hrys

azin

z D

extr

ansu

lfat

eso

dium

( DS-

M-1

) 3

3-D

imet

hoxy

benz

idin

e2H

Cl

33

-Dim

ethy

lben

zidi

ne2

HC

lz Z

-Eth

yl-O

NN

-azo

xym

etha

ne1

-Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

Glu

-P-1

z G

lu-P

-2z

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

IQz

o-N

itro

anis

olez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

Phe

nazo

pyri

dine

HC

lz P

hIP

HC

lz C

Ia

cid

red

114

44

-Thi

odia

nilin

ez T

ribr

omom

etha

ney

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez

Liv

erD

og2

33

-Dic

hlor

oben

zidi

ne4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line

)H

amst

er16

2-A

cety

lam

ino

uore

nez

pp

-DD

Ey

12-

Dim

ethy

lhyd

razi

ne2

HC

lH

exac

hlor

oben

zene

z H

ydra

zine

sulf

atez

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z N

-Met

hyl-

N-f

orm

ylhy

draz

ine

Met

hylh

ydra

zine

Met

hyln

itros

amin

o-N

N-d

imet

hyle

thyl

amin

eN

-Nitr

oso-

13-

oxaz

olid

ine

Nit

roso

-2-o

xopr

opyl

etha

nola

min

eN

-Nitr

osoa

llyl-

2-ox

opro

pyla

min

eN

-Nit

roso

azet

idin

eN

-Nit

roso

mor

phol

ine

N-N

itros

opip

erid

inez

N-N

itros

opyr

rolid

inez

Mou

se23

1A

-a-C

Ace

tam

inop

henz

2-A

cety

lam

ino

uore

nez

Aci

uor

fen

Ald

rinz

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

min

o-2-

met

hyla

nthr

aqui

none

z 2-

Am

inoa

nthr

aqui

none

z 4-

Am

inod

iphe

nyl

2-A

min

odip

heny

lene

oxid

e3-

Am

inot

riaz

olez

Ara

mite

z A

rocl

or12

54y

Aur

amin

e-O

z B

enzi

dine

2H

Cl

Ben

zofu

ranz

Ben

zyla

ceta

tey

3-B

enzy

lsyd

none

-4-a

ceta

mid

ez B

is( 2

-chl

oro-

1-m

ethy

leth

yl) e

ther

tec

hnic

algr

adey

Bis

-2-c

hlor

oeth

ylet

her

Bis

-2-h

ydro

xyet

hyld

ithio

carb

amic

acid

pot

assi

umC

Id

irec

tbla

ck38

CI

dir

ectb

lue

218z

HC

blue

no1

z H

Cbl

ueno

1( p

uri

ed)

Bro

mod

ichl

orom

etha

nez

13-

But

adie

nez

But

ylat

edhy

drox

ytol

uene

y 1

1-di

-n-B

utyl

hydr

azin

eC

apta

folz

Car

bazo

le

Car

bon

tetr

achl

orid

ez C

hlor

alhy

drat

eC

hlor

ambe

ny C

hlor

dane

tec

hnic

algr

adey

Chl

oren

dic

acid

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

1-

Chl

oro-

2-ni

trob

enze

ney

1-C

hlor

o-4-

nitr

oben

zene

y 4-

Chl

oro-

m-p

heny

lene

diam

inez

4-C

hlor

o-o-

phen

ylen

edia

min

ez 5-

Chl

oro-

o-to

luid

iney

642

[ 4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

] ace

ticac

idz

4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

( N-b

-hyd

roxy

ethy

l)ac

etam

idez

Chl

oroa

ceta

ldeh

yde

p-C

hlor

oani

line

HC

lz C

hlor

oben

zila

tey

Chl

orod

ibro

mom

etha

ney

Chl

orof

orm

z C

hlor

opre

nez

Chr

ysaz

inz

CI-

924

Cin

nam

ylan

thra

nila

tez

Cip

ro

brat

ez C

lobu

zari

ty C

ompo

und

LY17

1883

Cou

mar

inz

p-C

resi

dine

z C

upfe

rron

z C

ycla

mat

eso

dium

y C

yclo

chlo

roti

neC

ypro

tero

neac

etat

ep

p-D

DD

y p

p-D

DE

y D

DT

z D

ialla

te2

4-D

iam

inot

olue

nez

24-

Dia

min

otol

uene

2H

Clz

35-

Dic

hlor

o-( N

-11

-dim

ethy

l-2-

prop

ynyl

) ben

zam

ide

26-

Dic

hlor

o-p-

phen

ylen

edia

min

ey D

ichl

oroa

cetic

acid

z 1

4-D

ichl

orob

enze

nez

12-

Dic

hlor

opro

pane

y D

icof

oly

Die

ldri

nz D

ifta

lone

34

-Dih

ydro

coum

arin

z D

ihyd

rosa

frol

ez 2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 1

1-D

imet

hylh

ydra

zine

y 1

4-D

ioxa

nez

55-

Dip

heny

lhyd

anto

iny

Dip

yron

ey D

oxyl

amin

esu

ccin

atez

Est

rago

led

l-E

thio

nine

z o-

Eth

oxyb

enza

mid

eN

-Eth

yl-N

-for

myl

hydr

azin

eE

thyl

ene

imin

eE

thyl

ene

thio

urea

z 2-

Eth

ylhe

xano

ly di

( 2-E

thyl

hexy

l)ad

ipat

ey di

( 2-E

thyl

hexy

l)ph

thal

atez

4-F

luor

o-4-

amin

odip

heny

lF

uran

z Fu

rfur

alz

Gen

tian

viol

etG

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

Gri

seof

ulvi

nH

CD

Dm

ixtu

rez

Hep

tach

lory

Hex

achl

orob

enze

nez

a-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

z b

-12

34

56

-Hex

achl

oroc

yclo

hexa

nec

-12

34

56

-Hex

achl

oroc

yclo

hexa

ney

Hex

achl

oroc

yclo

hexa

ne

tech

nica

lgra

deH

exac

hlor

oeth

anez

Hex

anal

met

hylf

orm

ylhy

draz

one

Hyd

razi

nesu

lfat

ez H

ydra

zobe

nzen

ez H

ydro

quin

onez

N-H

ydro

xy-2

-ac

etyl

amin

ouo

rene

z 1

-Hyd

roxy

estr

agol

e2-

Hyd

roxy

ethy

lhyd

razi

ne1

-Hyd

roxy

safr

olez

IQz

Ison

iazi

dz Is

opre

neK

epon

ez L

eupe

ptin

Lov

asta

tinL

uteo

skyr

inM

alon

alde

hyde

sod

ium

saltz

MeA

-a-C

acet

atez

MeI

QM

eIQ

xz M

ethi

dath

ion

3-M

etho

xy-4

-am

inoa

zobe

nzen

eM

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z N

-Met

hyl-

N-f

orm

ylhy

draz

ine

3-M

ethy

lbut

anal

met

hylf

orm

ylhy

draz

one

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nili

ne)

2HC

ly M

ethy

lene

chlo

ride

z 4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Met

hylh

ydra

zine

N-M

ethy

lola

cryl

amid

ey M

ethy

lphe

nida

teH

Cly

Mic

hler

rsquoske

tone

z M

irex

z 1

5-N

apht

hale

nedi

amin

ez 2-

Nap

hthy

lam

inez

Nit

hiaz

idez

3-N

itro-

p-ac

etop

hene

tidey

5-N

itro-

o-an

isid

inez

2-N

itro

-p-p

heny

lene

diam

iney

5-N

itro

-o-t

olui

dine

y 5-

Nitr

oace

naph

then

ez o-

Nitr

oani

sole

z N

itrob

enze

nez

6-N

itrob

enzi

mid

azol

ey N

itro

fenz

Nit

rom

etha

nez

Nitr

osod

ibut

ylam

inez

N-N

itros

odim

ethy

lam

inez

p-N

itros

odip

heny

lam

inez

N-N

itro

sohe

xam

ethy

lene

imin

eN

-Nit

roso

pipe

ridi

nez

Non

abro

mob

iphe

nyl

Och

rato

xin

Az

Oxa

zepa

my

44

-Oxy

dian

iline

z Pe

ntac

hlor

oeth

aney

Pent

achl

oron

itrob

enze

ney

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y 2

34

56-

Pen

tach

loro

phen

olt

echn

ical

grad

ez P

enta

nalm

ethy

lfor

myl

hydr

azon

eP

hena

zopy

ridi

neH

Clz

Phe

noba

rbit

aly

Phen

obar

bita

lso

dium

z Ph

enyl

buta

zone

z o-

Phen

ylen

edia

min

e2H

Clz

Pipe

rony

l-bu

toxi

dez

Pipe

rony

lsul

foxi

dey

Poly

brom

inat

edbi

phen

ylm

ixtu

rez

Prob

enec

idy

N-N

-Pro

pyl-

N-f

orm

ylhy

draz

ine

Damp

Cre

dno

5z

Rif

ampi

ciny

Rip

azep

amy

p-R

osan

iline

HC

lz S

afro

lez

Sali

cyla

zosu

lfap

yrid

inez

Sel

eniu

mdi

ethy

ldith

ioca

rbam

ate

Sel

eniu

msu

lde

z S

trob

ane

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

11

12-

Tetr

achl

oroe

than

ey 1

12

2-Te

trac

hlor

oeth

aney

Tetr

achl

oroe

thyl

enez

Tetr

achl

orvi

npho

sy Te

tra

uoro

-m-p

heny

lene

diam

ine

2HC

ly Te

tra

uoro

ethy

lene

z Te

trah

ydro

fura

nz T

hioa

ceta

mid

ez 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

m-T

olui

dine

HC

ly o-

Tolu

idin

eH

Clz

p-To

luid

ine

HC

ly To

xaph

eney

T-2

toxi

nT

riam

tere

ney

Tri

chlo

roac

etic

acid

y 2

46-

Tri

chlo

roan

iline

y 1

12-

Tri

chlo

roet

hane

y T

rich

loro

ethy

lene

z T

rich

loro

ethy

lene

( wit

hout

epic

hlor

ohyd

rin)

y 2

46-

Tri

chlo

roph

enol

z 1

23-

Tri

chlo

ropr

opan

ez T

ri

ural

int

echn

ical

grad

ey 2

45-

Tri

met

hyla

nili

nez

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nilin

eH

Clz

24

6-T

rini

tro-

13-

dim

ethy

l-5-

tert

-but

ylbe

nzen

eT

ris(

2-ch

loro

ethy

l)ph

osph

atez

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez T

ris(

2-et

hylh

exyl

) pho

spha

tey

Trp

-P-1

acet

atez

Trp

-P-2

acet

atez

Ure

than

ez V

inyl

carb

amat

eV

inyl

uo

ride

z 2

5-X

ylid

ine

HC

lz C

Id

ispe

rse

yell

ow3z

Zea

rale

none

y

Mon

key

8A

ato

xin

B1y

Cyc

asin

and

met

hyla

zoxy

met

hano

lace

tate

IQ

z N

-Nitr

osod

ieth

ylam

ine

N-N

itro

sodi

prop

ylam

ine

N-N

itro

sopi

peri

dine

z S

teri

gmat

ocys

tinz

Ure

than

ez

Rat

206

Ace

tam

idez

Ace

tam

inop

henz

Ace

toxi

me

2-A

cety

lam

ino

uore

nez

A

atox

icol

A

atox

inB

y 1A

at

oxin

cru

dez

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

min

o-2-

met

hyla

nthr

aqui

none

z 2-

Am

inoa

nthr

aqui

none

z o-

Am

inoa

zoto

luen

ey 11

-Am

inou

ndec

anoi

cac

idy

Ara

mit

ez A

rocl

or12

60A

uram

ine-

Oz

Azo

xym

etha

neB

emit

radi

ne

Ben

zidi

ne3

-Ben

zyls

ydno

ne-4

-ace

tam

idez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

CI

dir

ectb

lue

15

Bro

mod

ichl

orom

etha

nez

Bud

eson

ide

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Chl

oren

dic

acid

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 2-

Chl

oro-

5-( 3

5-d

imet

hylp

iper

idin

osul

phon

yl) b

enzo

icac

id[

4-C

hlor

o-6-

( 23

-xy

lidi

no) -

2-py

rim

idin

ylth

io] a

ceti

cac

idz

4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

( N-b

-hyd

roxy

ethy

l)ac

etam

idez

Chl

orob

enze

ney

Chl

orof

orm

z 3-

( p-C

hlor

ophe

nyl)

-11

-dim

ethy

lure

ay C

ipro

bra

tez

Cliv

orin

eC

lob

rate

y C

loph

enA

30C

oum

arin

z p-

Cre

sidi

nez

Cro

tona

ldeh

yde

Cup

ferr

onz

Cyc

lope

ntan

one

oxim

eD

DT

z D

ecab

rom

odip

heny

loxi

dey

Deh

ydro

epia

ndro

ster

one

Deh

ydro

epia

ndro

ster

one

acet

ate

24-

Dia

min

otol

uene

z 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ibro

moe

than

ez D

ichl

oroa

ceti

cac

idz

Dic

hlor

oace

tyle

nez

NN

-Die

thyl

-4-(

4-[

pyri

dyl-

1-o

xide

] azo

) ani

line

Die

thyl

stil

best

rolz

Dim

etho

xane

3

3-D

imet

hoxy

benz

idin

e2H

Cl

56-

Dim

etho

xyst

erig

mat

ocys

tinN

N-D

imet

hyl-

4-am

inoa

zobe

nzen

e6-

Dim

ethy

lam

ino-

44-

diph

enyl

-3-h

epta

nola

ceta

teH

Cly

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hyln

itram

ine

Din

itros

ohom

opip

eraz

ine

26-

Din

itro

tolu

ene

24-

Din

itrot

olue

ne( c

onta

inin

g1

0-1

52

6-di

nitr

otol

uene

)z

Din

itrot

olue

net

echn

ical

grad

e( 2

4( 7

7) -

and

26

( 19

) -)

14-

Dio

xane

z D

ipen

tyln

itro

sam

ine

Dox

ylam

ine

succ

inat

ez E

thin

yles

trad

iol

Eth

ioni

ne

dl-E

thio

nine

z 4-

Eth

oxy-

phen

ylur

eaE

thyl

alco

holy

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neE

thyl

ene

thio

urea

z di

( 2-E

thyl

hexy

l)ph

thal

atez

Flu

cona

zole

y N

-(2-

Flu

oren

yl) -

22

2-tr

iuo

roac

etam

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

Fum

onis

inB

1F

uran

z Fu

rfur

alz

Glu

-P-1

z G

lu-P

-2z

FDamp

Cgr

een

no1

y H

CD

Dm

ixtu

rez

Hex

achl

orob

enze

nez

a-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

z H

ydra

zine

z H

ydra

zine

sulf

atez

Hyd

razo

benz

enez

Hyd

roch

loro

uor

ocar

bon

123

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z 1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-nitr

oso-

3-ch

loro

ethy

lure

a1

-Hyd

roxy

safr

olez

IQz

IQH

Cl

Ison

iazi

dz K

epon

ez L

asio

carp

ine

MeA

-a-C

acet

atez

MeI

Qxz

Met

hapy

rile

neH

Cl

Z-M

ethy

l-O

NN

-azo

xyet

hane

Met

hylc

arba

mat

ey M

ethy

lclo

fena

pate

z 3

-Met

hyl-

4-di

met

hyla

min

oazo

benz

ene

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

4-( 4

-N-M

ethy

l-N

-nit

rosa

min

osty

ryl)

quin

olin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line

) 4

4-M

ethy

lene

dian

ilin

e2H

Clz

4-( M

ethy

lnit

rosa

min

o)-1

-(3-

pyri

dyl)

-1-(

buta

none

) M

etro

nida

zole

z M

ichl

errsquos

keto

nez

Mir

exz

Mon

ocro

tali

neN

afen

opin

Nit

rite

sod

ium

y N

itrob

enze

nez

2-N

itro

buta

ne2

-Nit

ro

uore

ne3

-Nit

rope

ntan

eN

-Nitr

oso-

bis-

( 44

4-t

ri

uoro

-N-b

utyl

) am

ine

1-N

itros

o-5

6-di

hydr

oura

cil

N-N

itro

so-2

3-d

ihyd

roxy

prop

ylet

hano

lam

ine

1-N

itros

o-1-

hydr

oxye

thyl

-3-c

hlor

oeth

ylur

ea1

-Nitr

oso-

1-( 2

-hyd

roxy

prop

yl) -

3-ch

loro

ethy

lure

aN

-Nitr

oso-

( 2-h

ydro

xypr

opyl

) -( 2

-hyd

roxy

ethy

l)am

ine

N-N

itros

o-N

-met

hyl-

N-d

odec

ylam

ine

Nit

roso

-N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

e

( Con

tinue

don

next

page

)

643

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

N-N

itro

so-N

-met

hyld

ecyl

amin

e3-

Nit

roso

-2-o

xazo

lidin

one

Nit

roso

-2-o

xopr

opyl

etha

nola

min

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osoa

llyl

etha

nola

min

eN

-Nit

roso

bis(

2-ox

opro

pyl)

amin

eN

itro

sodi

buty

lam

inez

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

imet

hyla

min

ez p-

Nitr

osod

iphe

nyla

min

ez N

-Nit

roso

dipr

opyl

amin

eN

itros

odod

ecam

ethy

lene

imin

eN

-Nit

roso

ephe

drin

eN

itro

soet

hylm

ethy

lam

ine

Nitr

osoh

epta

met

hyle

neim

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

met

hyl-

( 2-h

ydro

xyet

hyl)

amin

eN

-Nitr

osom

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

-Nitr

osom

ethy

l(2-

oxop

ropy

l)am

ine

N-N

itro

som

ethy

l-( 2

-tos

ylox

yeth

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eN

-Nit

roso

mor

phol

ine

N-N

itros

opip

erid

inez

N-N

itro

sopy

rrol

idin

ez N

-Nit

roso

thia

ldin

eo-

Nit

roso

tolu

ene

Nor

lest

rinz

N-(

9-O

xo-2

-uo

reny

l)ac

etam

ide

44

-Oxy

dian

iline

z 2

34

56-

Pent

achl

orop

heno

lte

chni

calg

rade

z P

etas

iten

ine

Phe

noba

rbit

als

odiu

mz

1-P

heny

lazo

-2-n

apht

holy

o-P

heny

lene

diam

ine

2HC

lz P

iper

onyl

buto

xide

z P

olyb

rom

inat

edbi

phen

ylm

ixtu

rez

Pre

dnis

olon

eP

yril

amin

em

alea

tey

CI

aci

dre

d11

4C

Ip

igm

entr

ed3z

Damp

Cre

dno

5z

Damp

Cre

dno

9y

FD

ampC

red

no1

p-

Ros

anili

neH

Clz

Saf

role

z Se

leni

umsu

lde

z Se

nkir

kine

Ste

rigm

atoc

ystin

z S

ymph

ytin

eTa

mox

ifen

citr

atez

Telo

neII

tec

hnic

algr

adez

33

44

-Te

traa

min

obip

heny

l4H

Clz

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

auo

roet

hyle

nez

Thi

oace

tam

idez

44

-Thi

odia

nilin

ez To

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

Tri

amci

nolo

neac

eton

ide

24

5-T

rim

ethy

lani

line

z 2

45-

Tri

met

hyla

nili

neH

Clz

24

6-T

rim

ethy

lani

line

HC

lz T

rini

trog

lyce

rin

Trp

-P-1

acet

atez

Trp

-P-2

acet

atez

Vin

ylac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

CI

dis

pers

eye

llow

3z

Tre

esh

rew

1A

ato

xin

B1y

Lun

gH

amst

er3

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

1-N

itro

so-3

45

-tri

met

hylp

iper

azin

eM

ouse

116

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-is

onic

otin

oylh

ydra

zine

A

llyl

hydr

azin

eH

Cl

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

Are

coli

neH

Cl

5-A

zacy

tidi

nez

Ben

zene

z B

enzo

fura

nz B

enzo

tric

hlor

ide

Ben

zoyl

hydr

azin

eB

enzy

lhyd

razi

ne2

HC

l2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 2-c

hlor

o-1-

met

hyle

thyl

) eth

er

tech

nica

lgra

dey

Bis

-(ch

loro

met

hyl)

ethe

rz 1

3-B

utad

iene

z N

-n-B

utyl

-N-f

orm

ylhy

draz

ine

But

ylat

edhy

drox

ytol

uene

y 1

1-di

-n-B

utyl

hydr

azin

en-

But

ylhy

draz

ine

HC

l1

2-di

-N-B

utyl

hydr

azin

e2H

Cl

Caf

feic

acid

z C

arba

myl

hydr

azin

eH

Cl

1-C

arba

myl

-2-p

heny

lhyd

razi

neC

hlor

ambu

cilz

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z C

oum

arin

z C

yclo

phos

pham

idez

Dac

arba

zine

z D

amin

ozid

ez p

p-D

DD

y D

DT

z 1

1-D

iall

ylhy

draz

ine

12-

Dia

llyl

hydr

azin

e2H

Cl

Dib

enz(

ah)

anth

race

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

Dib

rom

odul

cito

lz 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

12-

Dic

hlor

oeth

anez

12-

Dif

orm

ylhy

draz

ine

Dih

ydro

safr

olez

25-

Dim

etho

xy-4

-am

inos

tilbe

nez

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

a-E

cdys

one

Est

radi

olm

usta

rdy

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylen

eim

ine

Eth

ylen

eox

idez

Eth

ylhy

draz

ine

HC

l5-

Flu

orou

raci

ly Fo

rmyl

hydr

azin

eG

lyci

dolz

c-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

y H

exan

alm

ethy

lfor

myl

hydr

azon

eH

ydra

zine

z H

ydra

zine

sulf

atez

IQz

Isob

utyl

nitr

itez

Ison

iazi

dz Is

onic

otin

icac

idva

nilly

liden

ehyd

razi

de

Isop

rene

Lov

asta

tinM

eIQ

xz M

elph

alan

z 1-

Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m

N-M

ethy

l-N

-for

myl

hydr

azin

eM

ethy

lmet

hane

sulf

onat

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eM

ethy

lene

chlo

ride

z M

ethy

lhyd

razi

ne

Met

hylh

ydra

zine

sulf

ate

( N-6

) -( M

ethy

lnit

roso

) ade

nine

(N

-6) -

( Met

hyln

itro

so) a

deno

sine

N-M

ethy

lola

cryl

amid

ey M

etro

nida

zole

z M

olyb

denu

mtr

ioxi

dey

Mon

oace

tylh

ydra

zine

Nap

htha

lene

15

-Nap

htha

lene

diam

inez

Nic

otin

icac

idhy

draz

ide

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez 3-

Nitr

o-3-

hexe

nez

Nit

robe

nzen

ez N

itrom

etha

nez

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

dim

ethy

lam

inez

N-N

itros

ohex

amet

hyle

neim

ine

N-N

itro

sopi

peri

dine

z O

zone

y Pe

ntan

alm

ethy

lfor

myl

hydr

azon

en-

Pen

tylh

ydra

zine

HC

lPh

enes

teri

nz Ph

enyl

ethy

lhyd

razi

nesu

lfat

eP

roca

rbaz

ine

HC

lz N

-N-P

ropy

l-N

-for

myl

hydr

azin

eP

ropy

lhyd

razi

neH

Cl

Sel

eniu

msu

lde

z S

trep

tozo

toci

nz Su

lfal

late

z Te

lone

IIt

echn

ical

grad

ez 3

34

4-T

etra

amin

obip

heny

l4H

Clz

Tetr

anitr

omet

hane

z T-

2to

xin

Tri

chlo

roet

hyle

nez

Tri

ura

lint

echn

ical

grad

ey 2

45-

Tri

met

hyla

nilin

eH

Clz

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez U

reth

anez

Vin

ylch

lori

dez

Vin

ylu

orid

ez V

inyl

iden

ech

lori

dey

24-

Xyl

idin

eH

Cly

Mon

key

1U

reth

anez

Rat

551-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro

-2-f

uryl

) -1

34-

oxad

iazo

le2

-Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-5-

nitr

othi

azol

ey 1-

Am

yl-1

-nitr

osou

rea

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is-(

chlo

rom

ethy

l)et

herz

HC

blue

no1

z B

rom

oeth

anez

N-n

-But

yl-N

-nit

roso

urea

Cad

miu

mch

lori

deC

adm

ium

sulp

hate

( 11

) 1-

Chl

oroe

thyl

nitr

oso-

3-( 2

-hyd

roxy

prop

yl) u

rea

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z 1

2-D

ibro

moe

than

ez D

imet

hylh

ydro

gen

phos

phit

ey tr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-

[ 2-(

5-ni

tro-

2-fu

ryl)

viny

l] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

12-

Epo

xybu

tane

y 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

Hyd

razi

nez

Hyd

razi

nesu

lfat

ez 1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

Isob

utyl

nitr

itez

Ison

iazi

dz 4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4-

( Met

hyln

itros

amin

o)-1

-(3-

pyri

dyl)

-1-b

utan

ol4

-(M

ethy

lnit

rosa

min

o)-1

-(3-

pyri

dyl)

-1-(

buta

none

) N

-[ 3

-(5-

Nitr

o-2-

fury

l)-

12

4-ox

adia

zole

-5-y

l] -m

ethy

lace

tam

ide

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

3-N

itro-

3-he

xene

z 5-

Nitr

oace

naph

then

ez N

-Nit

roso

-bis

-(4

44-

tri

uoro

-N-b

utyl

) am

ine

N-N

itros

o-N

-met

hyl-

N-d

odec

ylam

ine

N-N

itros

o-N

-met

hyl-

N-t

etra

decy

lam

ine

N-N

itro

so-N

-met

hyld

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

lure

az N

-Nitr

osob

is( 2

-hyd

roxy

prop

yl)

amin

eN

-Nitr

osob

is-2

3-d

ihyd

roxy

prop

ylam

ine

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itros

odim

ethy

lam

inez

N-N

itro

soep

hedr

ine

Nitr

osoe

thyl

met

hyla

min

eN

-Nit

roso

met

hyl

N-N

itro

som

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eC

Ia

cid

red

114

Sod

ium

dich

rom

ate

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

anit

rom

etha

nez

24

5-T

rim

ethy

lani

line

z 2

46-

Tri

met

hyla

nili

neH

Clz

Vin

ylch

lori

dez

Mam

mar

ygl

and

Dog

1Ly

nest

reno

lH

amst

er1

Vin

ylch

lori

dez

Mou

se24

5-A

zacy

tidin

ez B

enze

nez

CI

dir

ectb

lack

381

3-B

utad

iene

z C

alci

fero

lC

hlor

opre

nez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Die

thyl

stilb

estr

olz

a-E

cdys

one

Est

radi

olE

thyl

ene

oxid

ez F

uros

emid

ey G

lyci

dolz

Gri

seof

ulvi

nIs

onia

zidz

Ison

icot

inic

acid

vani

llylid

eneh

ydra

zide

( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Nitr

oben

zene

z R

eser

pine

z Su

lfal

late

z V

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y

644

Rat

102

4-A

cety

lam

inob

iphe

nyl

2-A

cety

lam

ino

uore

nez

Acr

onyc

ine

Acr

ylam

ide

Acr

ylon

itri

leA

F-2

z 1-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro-

2-fu

ryl)

-13

4-

oxad

iazo

le2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

e2-

Am

ino-

5-ni

trot

hiaz

oley

4-A

min

odip

heny

lHC

l1-

Am

yl-1

-nit

roso

urea

Atr

azin

ey B

emit

radi

ne

Ben

zidi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

4-B

is( 2

-hyd

roxy

ethy

l)am

ino-

2-( 5

-nit

ro-2

-thi

enyl

) qui

nazo

line

13-

But

adie

nez

N-n

-But

yl-N

-nitr

osou

rea

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Car

boxy

met

hyln

itros

oure

aC

hlor

ambu

cilz

Chl

orop

rene

z C

ytem

bena

y D

acar

bazi

nez

N-1

-Dia

ceta

mid

ouo

rene

46

-Dia

min

o-2-

( 5-n

itro-

2-fu

ryl)

-S-t

riaz

ine

24-

Dia

min

oani

sole

sulf

atez

24-

Dia

min

otol

uene

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dib

rom

oman

nito

lz 1

3-D

ibut

yl-1

-nit

roso

urea

33

-Dic

hlor

oben

zidi

ne1

2-D

ichl

oroe

than

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

12-

Dim

ethy

l-5-

nitr

oim

idaz

ole

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lam

inoe

thyl

nitr

osoe

thyl

urea

nitr

ite

salt

33

-Dim

ethy

lben

zidi

ne2

HC

lz 2-

( 22

-Dim

ethy

lhyd

razi

no) -

4-( 5

-nitr

o-2-

fury

l)th

iazo

le

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

24-

Dio

xane

z 1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

6-di

nitr

otol

uene

)zN

-(2-

Fluo

reny

l)-2

22

-tri

uo

roac

etam

ide

Form

icac

id2-

( 4-m

ethy

l-2-

thia

zoly

l)hy

draz

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-

thia

zoly

l] hyd

razi

dez

Gly

cido

lz H

exam

ethy

lmel

amin

eN

-Hex

ylni

tros

oure

a2-

Hyd

razi

no-4

-(p-

amin

ophe

nyl)

thia

zole

z 2-

Hyd

razi

no-4

-( 5

-nit

ro-2

-fur

yl) t

hiaz

olez

2-H

ydra

zino

-4-(

p-ni

trop

heny

l)th

iazo

lez

Hyd

razo

benz

enez

1-( 2

-Hyd

roxy

ethy

l)-3

-[( 5

-nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

e1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

1-(

2-H

ydro

xyet

hyl)

-1-n

itros

oure

az In

dom

etha

cin

IQz

IQH

Cl

Ison

iazi

dz 2-

Met

hoxy

-3-a

min

odib

enzo

fura

n4-

Met

hyl-

1-[(

5-ni

trof

urfu

rylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

-(N

-Met

hyl-

N-n

itro

soca

rbam

oyl)

-l-o

rnit

hine

3-M

ethy

lcho

lant

hren

e4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line)

Met

hyle

nech

lori

dez

Met

roni

dazo

lez

l-5-

Mor

phol

inom

ethy

l-3-

[(5-

nitr

ofur

fury

lide

ne) a

min

o]-

2-ox

azol

idin

one

HC

lN

ithia

zide

z 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

3-( 5

-Nitr

o-2-

fury

l)-i

mid

azo(

12-

a)

pyri

dine

z 4-

( 5-N

itro-

2-fu

ryl)

thia

zole

N

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

ide

NN

-[6-

( 5-N

itro

-2-f

uryl

) -S-

tria

zine

-24

-diy

l] bis

acet

amid

e5-

Nitr

oace

naph

then

ez 1-

[(5-

Nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

itrom

etha

nez

1-N

itrop

yren

eN

orle

stri

nz O

chra

toxi

nA

z N

-(9-

Oxo

-2-

uore

nyl)

acet

amid

ePh

enac

etin

z Ph

enes

teri

nz Ph

IPH

Clz

Proc

arba

zine

HC

lz Pr

opan

esu

lton

e1

2-Pr

opyl

ene

oxid

ez St

yren

ey Su

lfal

late

z 4

4-S

ulfo

nylb

isac

etan

ilid

eTo

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uor

o-N

-[4-

( 5-n

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

idez

Trp

-P-2

acet

atez

Vin

ylch

lori

dez

FD

ampC

viol

etno

1y

Mes

ovar

ium

Rat

2Sa

lbut

amol

Ter

buta

line

Myo

card

ium

Mou

se2

Est

radi

olm

usta

rdy

Phen

este

rinz

Nas

alca

vity

bB

ush

baby

1N

-Nitr

osod

ieth

ylam

ine

Ham

ster

11A

ceta

ldeh

yde

Dia

llyln

itros

amin

eD

imet

hylc

arba

myl

chlo

ride

Hyd

razi

nez

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osom

ethy

l-2

3-di

hydr

oxyp

ropy

lam

ine

N-N

itros

omor

phol

ine

N-N

itros

onor

nico

tine

N-N

itros

opip

erid

inez

Mou

se6

Ally

lgly

cidy

leth

ery

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 1

2-D

ibro

moe

than

ez Fo

rmal

dehy

dez

N-N

itro

sohe

xam

ethy

lene

imin

e1

2-Pr

opyl

ene

oxid

ez

Rat

43A

ceta

ldeh

yde

Acr

ylon

itril

e1-

Azo

xypr

opan

eB

enze

nez

Bis

-(ch

loro

met

hyl)

ethe

rz p-

Cre

sidi

nez

Dia

llyln

itros

amin

e1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dim

ethy

lnitr

amin

eD

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

e1

4-D

ioxa

nez

12-

Epo

xybu

tane

y Z

-Eth

yl-O

NN

-azo

xyet

hane

E

thyl

benz

ene

Eth

ylni

tros

ocya

nam

ide

Form

alde

hyde

z H

exam

ethy

lpho

spho

ram

ide

Hyd

razi

nez

N-N

itro

so-N

-met

hyld

ecyl

amin

edi

( N-N

itro

so) -

perh

ydro

pyri

mid

ine

N-N

itros

o(2

22-

tri

uoro

ethy

l)et

hyla

min

e1-

Nitr

oso-

34

5-tr

imet

hylp

iper

azin

eN

-Nitr

osoa

llyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyle

than

olam

ine

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

dipr

opyl

amin

eN

itros

oeth

ylm

ethy

lam

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nitr

osom

ethy

l-( 2

-hyd

roxy

ethy

l)am

ine

N-N

itro

som

ethy

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

norn

icot

ine-

1-N

-oxi

de

N-N

itro

sopi

peri

dine

z P

hena

cetin

z Ph

enyl

glyc

idyl

ethe

r1

2-Pr

opyl

ene

oxid

ez V

inyl

acet

atez

Vin

ylch

lori

dez

Ner

vous

Mou

se3

13-

But

adie

nez

N-N

itros

odim

ethy

lam

inez

Pro

carb

azin

eH

Clz

syst

emR

at21

Acr

ylam

ide

Acr

ylon

itril

eB

rom

oeth

anez

Chl

oram

buci

lz 1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

eC

yclo

phos

pham

idez

1-E

thyl

-1-n

itros

oure

aE

thyl

eneo

xide

z 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

eaG

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

R(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

S(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

M

ethy

lnit

ram

ine

N-N

itros

o-N

-met

hylu

reaz

N-N

itros

odie

than

olam

ine

1-P

heny

l-3

3-di

met

hyltr

iaze

neP

roca

rbaz

ine

HC

lz P

ropa

nesu

ltone

Vin

ylch

lori

dez

Ora

lcav

ityc

Ham

ster

4A

ceta

ldeh

yde

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itros

omor

phol

ine

N-N

itro

sopi

peri

dine

z

Mou

se3

N-N

itros

ohex

amet

hyle

neim

ine

12

3-T

rich

loro

prop

anez

Vin

ylac

etat

ez

Rat

32A

cryl

amid

eA

cryl

onitr

ile

Ben

zene

z 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

CI

dir

ectb

lue

15C

Id

irec

tblu

e21

8z C

hlor

opre

nez

3-D

iazo

tyra

min

eH

Cl

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

eG

lyci

dolz

IQz

MeA

-a-C

acet

atez

N-N

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

hydr

oxyp

ropy

lam

ine

Nit

roso

-23

-dih

ydro

xypr

opyl

-2-

oxop

ropy

lam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

itro

soam

ylur

etha

nN

-Nitr

osod

ieth

ylam

ine

Nit

roso

ethy

lure

than

N

itros

ohep

tam

ethy

lene

imin

e1-

Nitr

osoh

ydan

toin

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

thia

ldin

eN

-Nitr

osot

hiom

orph

olin

eC

Ia

cid

red

114

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tolu

eney

12

3-T

rich

loro

prop

anez

Xyl

ene

mix

ture

( m-x

ylen

eo-

xyle

nep

-xyl

ene)

Ova

ryM

ouse

10B

enze

nez

13-

But

adie

nez

Die

thyl

stil

best

rolz

N-M

ethy

lola

cryl

amid

ey 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

5-N

itroa

cena

phth

enez

1-[(

5-N

itro

furf

uryl

iden

e)am

ino]

hyda

ntoi

nz P

heno

lpht

hale

inz

Tam

oxif

enci

trat

ez 4-

Vin

ylcy

cloh

exen

ePa

ncre

asH

amst

er3

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

itro

so-2

6-d

imet

hylm

orph

olin

eN

itro

so-2

-oxo

prop

ylet

hano

lam

ine

Mon

key

1U

reth

anez

Rat

222-

Am

ino-

5-ni

trop

heno

ly 1-

( Am

inom

ethy

l)cy

cloh

exan

eace

ticac

idA

zase

rine

But

ylbe

nzyl

phth

alat

ey C

hlor

endi

cac

idz

Cin

nam

ylan

thra

nila

tez

Clo

bra

tey

Dic

hlor

vosz

Eth

ylal

coho

ly H

ydro

chlo

ro

uoro

carb

on12

3IQ

HC

lM

alon

alde

hyde

sod

ium

saltz

MeA

-a-C

acet

atez

2-M

erca

ptob

enzo

thia

zole

y M

ethy

lclo

fena

pate

z N

-(N

-Met

hyl-

N-n

itros

ocar

bam

oyl)

-l-o

rnit

hine

4-(

Met

hyln

itro

sam

ino)

-1-(

3-py

ridy

l)-1

-but

anol

4-(

Met

hyln

itros

amin

o)-1

-( 3

-pyr

idyl

) -1-

( but

anon

e)N

afen

opin

Nitr

ofen

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)z1

23

-Tri

chlo

ropr

opan

ez

Peri

tone

alM

ouse

8B

is-1

2-(

chlo

rom

etho

xy) e

than

eB

is-1

4-(

chlo

rom

etho

xy) -

p-xy

lene

Bis

-(ch

loro

met

hyl)

ethe

rz C

hlor

opre

nez

tran

s-1

4-D

ichl

orob

uten

e-2

cavi

tyD

imet

hylc

arba

myl

chlo

ride

Phe

noxy

benz

amin

eH

Clz

Tri

s-1

23-

( chl

orom

etho

xy) p

ropa

neR

at22

Acr

onyc

ine

Acr

ylam

ide

Act

inom

ycin

DA

nili

neH

Cly

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

rom

ate

pota

ssiu

mz

Chl

oroz

otoc

in

Cyt

embe

nay

Dap

sone

y 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

4-D

ioxa

nez

Eth

ylen

eox

idez

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz M

elph

alan

z N

-Met

hyl-

N4

-din

itros

oani

line

Mit

omyc

in-C

N-N

itro

so-2

24

-tri

met

hyl-

12-

dihy

droq

uino

line

poly

mer

Ph

enox

yben

zam

ine

HC

lz o-

Tolu

idin

eH

Clz

( Con

tinue

don

next

page

)

645

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Pitu

itar

ygl

and

Mou

se8

Die

thyl

stil

best

rolz

Eno

vid

Eth

ylen

eth

iour

eaz

Iodi

nate

dgl

ycer

olz

Isop

rene

Nor

lest

rinz

Pro

pylt

hiou

raci

lz Z

eara

leno

ney

Rat

73-

Am

inot

riaz

olez

12-

Dib

rom

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylal

coho

ly 2-

Mer

capt

oben

zoth

iazo

ley

Met

roni

dazo

lez

Nor

lest

rinz

Pros

tate

Rat

4C

adm

ium

chlo

ride

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

PhIP

HC

lz

Skin

Ham

ster

2U

reth

anez

Vin

ylch

lori

dez

Mou

se5

5-A

zacy

tidin

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Chl

orop

rene

z G

lyci

dolz

Thi

o-te

paz

Rat

332-

Ace

tyla

min

ouo

rene

z 3-

Am

ino-

9-et

hylc

arba

zole

mix

ture

z 1-

Azo

xypr

opan

e2-

Azo

xypr

opan

eB

enze

nez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

ol

tech

nica

lgra

dez

CI

dir

ectb

lue

15C

arbo

xym

ethy

lnitr

osou

rea

24-

Dia

min

oani

sole

sulf

atez

Dib

rom

odul

cito

lz D

ibro

mom

anni

tolz

Dim

etho

xane

2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

Dim

ethy

lvin

ylch

lori

dez

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

26-

dini

trot

olue

ne)z

1-E

thyl

nitr

oso-

3-( 2

-hyd

roxy

ethy

l)-u

rea

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz 1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

IQ

z L

asio

carp

ine

MeI

Qxz

N-(

N-M

ethy

l-N

-nitr

osoc

arba

moy

l)-l

-orn

ithi

ne

5-N

itro-

o-an

isid

inez

CI

aci

dre

d11

4p-

Ros

anili

neH

Clz

Thi

o-te

paz

Thi

oure

ay V

inyl

chlo

ride

z F

Damp

Cvi

olet

no1

y

Smal

lint

esti

neM

ouse

6C

apta

folz

Cap

tanz

N-E

thyl

-N-n

itro

-N-n

itro

sogu

anid

ine

Hyd

roge

npe

roxi

deN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-(

Tri

chlo

rom

ethy

lthi

o)ph

thal

imid

eM

onke

y1

Ure

than

ez

Rat

29A

cryl

onitr

ile

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is( 2

3-d

ibro

mop

ropy

l)ph

osph

ate

mag

nesi

umsa

lt4

-Bis

( 2-h

ydro

xyet

hyl)

amin

o-2-

( 5-n

itro

-2-t

hien

yl) q

uina

zolin

eC

Id

irec

tblu

e15

Car

boxy

met

hyln

itros

oure

a1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

e2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro

-2-f

uryl

)py

rim

idin

etr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-[

2-( 5

-nit

ro-2

-fur

yl) v

inyl

] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

Z-E

thyl

-ON

N-a

zoxy

met

hane

1-E

thyl

-1-n

itros

oure

aFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lu-P

-1z

Glu

-P-2

z IQ

z L

asio

carp

ine

N-M

ethy

l-N

-nitr

o-N

-nitr

osog

uani

dine

z N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez N

-Nitr

oso-

N-i

sobu

tylu

rea

3-N

itro

so-2

-oxa

zoli

dino

neN

itro

soet

hylu

reth

ane

PhI

PH

Clz

Pro

pane

sulto

neQ

uerc

etin

y C

Ia

cid

red

114

Trp

-P-2

acet

atez

Sple

enR

at7

Ani

line

HC

ly A

zobe

nzen

ey p-

Chl

oroa

nili

neH

Clz

Dap

sone

y o-

Nitr

osot

olue

neD

ampC

red

no9

y o-

Tolu

idin

eH

Clz

Stom

ach

Ham

ster

18A

F-2z

14-

Din

itros

o-2

6-di

met

hylp

iper

azin

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z H

ydra

zine

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] a

ceta

mid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

N-N

itro

so-2

3-d

ihyd

roxy

prop

yl-2

-hyd

roxy

prop

ylam

ine

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

-Nitr

oso-

ethy

l-2-

oxop

ropy

lure

aN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

itros

o-5-

met

hylo

xazo

lidon

eN

-Nit

roso

-N-m

ethy

lure

than

N-N

itros

o-1

3-ox

azol

idin

eN

-Nit

roso

-2-p

heny

leth

ylur

ea1

-Nit

roso

-34

5-t

rim

ethy

lpip

eraz

ine

Ure

than

ez V

inyl

chlo

ride

z

Mou

se63

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eA

ciu

orfe

nA

F-2

z 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

tran

s-5-

Am

ino-

3[2-

( 5-n

itro-

2-fu

ryl)

viny

l] -1

24-

oxad

iazo

leA

reco

line

HC

lB

enza

ldeh

ydey

Ben

zofu

ranz

Ben

zotr

ichl

orid

eB

enzy

lace

tate

y B

enzy

lchl

orid

ey B

rom

oeth

anol

13

-But

adie

nez

But

ylat

edhy

drox

yani

sole

z 1

1-di

-N-B

utyl

hydr

azin

eC

affe

icac

idz

Cap

tafo

lz C

arba

zole

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z3

-(C

hlor

omet

hyl)

pyri

dine

HC

lz C

hlor

opre

nez

2-C

hlor

opro

pana

l1-

Chl

orop

rope

neC

ypro

tero

neac

etat

e1

1-D

ially

lhyd

razi

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dic

hlor

vosz

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez D

imet

hylv

inyl

chlo

ride

z D

init

roso

pipe

razi

neE

stra

diol

mus

tard

y E

thyl

acry

late

z Fo

rmic

acid

2-[ 4

-( 5

-nit

ro-2

-fur

yl) -

2-th

iazo

lyl] h

ydra

zide

z G

lyci

dolz

2-H

ydra

zino

-4-(

5-ni

tro-

2-fu

ryl)

thia

zole

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

ICI

1628

46z

IQz

Isop

rene

Lov

asta

tin

MeI

Q1

-Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m3

-(5-

Nitr

o-2-

fury

l)-

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] f

orm

amid

ez N

-Nit

roso

-N

-met

hylu

reaz

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

hexa

met

hyle

neim

ine

N-N

itros

opip

erid

inez

b-P

ropi

olac

tone

z Se

sam

olz

Sty

rene

oxid

ez Te

lone

IIt

echn

ical

grad

ez N

-(T

rich

loro

met

hylth

io) p

htha

limid

e1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uo

ro-N

-[4-

( 5-n

itro

-2-f

uryl

) -2-

thia

zoly

l]ac

etam

idez

Tri

ur

alin

tec

hnic

algr

adey

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylac

etat

ez

Rat

85A

ceto

ne[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zone

1-A

ceto

xysa

frol

ey A

cryl

onitr

ile

1-A

llyl

-1-n

itro

sour

ea2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-ox

adia

zole

2-

Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-4-

( 5-n

itro

-2-f

uryl

) thi

azol

ez 1-

Am

yl-1

-nit

roso

urea

Ari

stol

ochi

cac

id

sodi

umsa

lt( 7

7A

AI

21

AA

II)

Ben

zene

z B

enzo

( a) p

yren

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

BL

-634

1H

Cl

N-n

-But

yl-N

-nitr

osou

rea

But

ylat

edhy

drox

yani

sole

z b

-But

yrol

acto

neC

affe

icac

idz

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z4

-Chl

oro-

o-ph

enyl

ened

iam

inez

Chl

oro

uoro

met

hane

3-

( Chl

orom

ethy

l)py

ridi

neH

Clz

Cip

rob

rate

z C

upfe

rron

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez 2

5-D

imet

hoxy

-4-a

min

osti

lben

ez D

imet

hylh

ydro

gen

phos

phit

ey 4

6-D

imet

hyl-

2-( 5

-nit

ro-2

-fu

ryl)

pyri

mid

ine

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lvin

ylch

lori

dez

Epi

chlo

rohy

drin

y E

thyl

acry

late

z E

thyl

ene

oxid

ez 2-

Flu

oroe

thyl

-nitr

osou

rea

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-

nitr

osou

reaz

1-( 3

-Hyd

roxy

prop

yl) -

1-ni

tros

oure

a1

-Hyd

roxy

safr

olez

ICI

1628

46z

Lox

tidin

eL

upit

idin

e3H

Cl

Mer

curi

cch

lori

dey

3-M

etho

xyca

tech

ol4

-Met

hoxy

phen

olN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-M

ethy

l-N

-nit

roso

benz

amid

e4-

Met

hylc

atec

hol

Met

hyln

itro

socy

anam

ide

3-( 5

-Nit

ro-2

-fur

yl) -

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

4-( 5

-Nit

ro-2

-fur

yl) t

hiaz

ole

2-N

itro

uo

rene

8-N

itro

quin

olin

eN

itro

so-B

aygo

nN

-Nit

roso

-23

-dih

ydro

xypr

opyl

-2-h

ydro

xypr

opyl

amin

eN

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

oxop

ropy

lam

ine

1-N

itro

so-3

5-d

imet

hyl-

4-be

nzoy

lpip

eraz

ine

N-N

itro

so-N

-met

hyl-

N-d

odec

ylam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itro

so-N

-met

hylu

reaz

Nit

roso

-12

36

-tet

rahy

drop

yrid

ine

N-N

itro

sobe

nzth

iazu

ron

Nitr

osod

ibut

ylam

inez

N-N

itros

odie

thyl

amin

eN

-Nit

roso

ephe

drin

eN

itros

oeth

ylur

etha

nO

mep

razo

ley

Phen

acet

inz

Piv

alol

acto

ney

b-P

ropi

olac

tone

z N

-Pro

pyl-

N-n

itro

-N-n

itro

sogu

anid

ine

12-

Pro

pyle

neox

idez

Ses

amol

z St

yren

eox

idez

Sulf

alla

tez

Telo

neII

tec

hnic

algr

adez

12

3-T

rich

loro

prop

anez

24

6-T

rim

ethy

lani

line

HC

lz

646

Subc

utan

eous

Mou

se4

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

2-D

ibro

moe

than

ez N

2-c

-Glu

tam

yl-p

-hyd

razi

nobe

nzoi

cac

idG

lyci

dolz

tissu

eR

at13

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ichl

oroe

than

ez D

imet

hoxa

ne1

4-D

ioxa

nez

MeA

-a-C

acet

atez

44

-Met

hyle

ne-b

is( 2

-met

hyla

nili

ne)

o-N

itro

soto

luen

ep-

Ros

anili

neH

Clz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 2

45-

Tri

met

hyla

nilin

eH

Clz

25-

Xyl

idin

eH

Clz

Test

isM

ouse

4D

ieth

ylst

ilbe

stro

lz Fi

nast

erid

eR

eser

pine

z Ta

mox

ifen

citr

atez

Rat

185-

Aza

cytid

inez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

3-B

utad

iene

z N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

Cad

miu

mch

lori

de

2-C

hlor

o-1

11-

tri

uoro

etha

ne1

1-D

ichl

oro-

1-u

oroe

than

eH

ydro

chlo

rou

oroc

arbo

n12

3M

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z M

etro

nida

zole

z N

-Nit

roso

dim

ethy

lam

inez

Oxo

linic

acid

y SD

Z20

0-11

01

11

2-Te

tra

uoro

etha

ney

Tri

chlo

roet

hyle

nez

Tri

nitr

ogly

ceri

nV

inyl

chlo

ride

z

Thy

roid

glan

dH

amst

er4

Hex

achl

orob

enze

nez

Hyd

razi

nez

Met

hylt

hiou

raci

lU

reth

anez

Mou

se18

3-A

min

o-4-

etho

xyac

etan

ilide

y H

Cbl

ueno

1z

tert

-But

ylal

coho

lz C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

24

-Dia

min

oani

sole

sulf

atez

Die

thyl

stil

best

rolz

Dox

ylam

ine

succ

inat

ez E

thio

nam

idey

Eth

ylen

eth

iour

eaz

44

-Met

hyle

nedi

anil

ine

2HC

lz 1

5-N

apht

hale

nedi

amin

ez N

itrob

enze

nez

Oxa

zepa

my

44

-Oxy

dian

iline

z C

Ip

igm

entr

ed3z

Sulf

amet

hazi

ne2

37

8-T

etra

chlo

rodi

benz

o-p-

diox

inz

44

-Thi

odia

nilin

ez

Rat

33A

cryl

amid

e3-

Am

inot

riaz

olez

o-A

nisi

dine

HC

lz B

emit

radi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

Chl

orop

rene

z 2

4-D

iam

inoa

niso

lesu

lfat

ez N

N-D

ieth

ylth

iour

eay

1-E

thyl

-1-n

itro

sour

ea

Eth

ylen

eth

iour

eaz

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Flu

vast

atin

Gly

cido

lz Io

dina

ted

glyc

erol

z Is

obut

eney

Mal

onal

dehy

des

odiu

msa

ltz

Met

him

azol

e4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Mir

exp

hoto

-N

itro

benz

enez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

44

-Oxy

dian

iline

z Pr

opyl

thio

urac

ilz p-

Ros

anil

ine

HC

lz 2

37

8-Te

trac

hlor

odib

enzo

-p-d

ioxi

nz 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tri

met

hylt

hiou

reay

Vin

ylac

etat

ez Z

inc

dim

ethy

ldith

ioca

rbam

atez

Uri

nary

blad

der

Dog

23

3-D

ichl

orob

enzi

dine

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nilin

e)H

amst

er3

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

acet

amid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

Mou

se12

2-A

cety

lam

ino

uore

nez

4-A

min

odip

heny

l2-

Am

inod

iphe

nyle

neox

ide

o-A

nisi

dine

HC

lz 4-

Chl

oro-

4-a

min

odip

heny

leth

erz

p-C

resi

dine

z 4-

Eth

ylsu

lpho

nyln

apht

hale

ne-1

-sul

fona

mid

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hena

cetin

z Te

lone

IIt

echn

ical

grad

ez U

raci

lz

Mon

key

12-

Nap

hthy

lam

inez

Rat

49A

ceta

min

ophe

nz A

llyli

soth

iocy

anat

ey 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

4-A

min

o-2-

nitr

ophe

noly

11-A

min

ound

ecan

oic

acid

y o-

Ani

sidi

neH

Clz

Ari

stol

ochi

cac

ids

odiu

msa

lt( 7

7A

AI

21

AA

II)

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

ispe

rse

blue

1y N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

4-C

hlor

o-o-

phen

ylen

edia

min

ez m

-Cre

sidi

ney

p-C

resi

dine

z C

yclo

phos

pham

idez

Die

thyl

ene

glyc

olD

imet

hyla

rsin

icac

idy

Fose

tylA

lIQ

HC

lM

eA-a

-Cac

etat

ez M

elam

iney

2-M

etho

xy-3

-am

inod

iben

zofu

ran

2-N

apht

hyla

min

ez N

itril

otri

acet

icac

idz

Nitr

ilot

riac

etic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez o-

Nitr

oani

sole

z N

-Nitr

oso-

N-m

ethy

l-N

-dod

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

l-N

-tet

rade

cyla

min

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itro

sodi

phen

ylam

iney

o-N

itros

otol

uene

N-O

xydi

ethy

lene

thio

carb

amyl

-N-o

xydi

ethy

lene

sulf

enam

ide

Phe

nace

tinz

Phen

azon

eo-

Phen

ylph

enat

eso

dium

y o-

Phen

ylph

enol

y P

otas

sium

bica

rbon

ate

Purp

urin

Que

rcet

iny

p-Q

uino

nedi

oxim

ey Sa

ccha

rin

sodi

umy

Sali

cyla

zosu

lfap

yrid

inez

o-To

luen

esul

fona

mid

eo-

Tolu

idin

eH

Clz

Trp

-P-2

acet

atez

Ura

cilz

Ute

rus

Ham

ster

1N

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aM

ouse

12B

rom

oeth

anez

Chl

oroe

than

ey D

acar

bazi

nez

12-

Dic

hlor

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylen

eox

idez

Gly

cido

lz ( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Proc

arba

zine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez T

rim

ethy

lpho

spha

tey

Vin

ylac

etat

ez

Rat

26A

cryl

amid

e1-

Ally

l-1-

nitr

osou

rea

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

myl

-1-n

itros

oure

aA

traz

iney

CI

dir

ectb

lue

15B

rom

ocri

ptin

em

esyl

atey

N-n

-But

yl-N

-nit

roso

urea

Cal

cium

valp

roat

eC

apta

nz 2-

Chl

oro-

11

1-tr

iuo

roet

hane

Dac

arba

zine

z D

amin

ozid

ez 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

lD

imet

hyla

min

oeth

ylni

tros

oeth

ylur

ean

itri

tesa

lt1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

ICR

F-1

59z

Isop

hosp

ham

idez

15-

Nap

htha

lene

diam

inez

Nit

robe

nzen

ez N

orle

stri

nz 4

4-T

hiod

iani

linez

Vin

ylac

etat

ez

Vag

ina

Mou

se1

AZ

Tz

Rat

2A

ZT

z N

-n-B

utyl

-N-n

itro

sour

ea( C

ontin

ued

onne

xtpa

ge)

647

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Vas

cula

rsy

stem

Ham

ster

91

2-D

imet

hylh

ydra

zine

2H

Cl

Gly

cido

lz H

exac

hlor

oben

zene

z N

-Nit

roso

-eth

yl-2

-oxo

prop

ylur

eaN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

-Nitr

oso-

oxop

ropy

lchl

oroe

thyl

urea

N-N

itro

so-o

xopr

opyl

urea

N-N

itros

o-2-

phen

ylet

hylu

rea

Vin

ylch

lori

dez

Mou

se59

A-a

-CN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-ph

enyl

hydr

azin

eA

llyl

hydr

azin

eH

Cl

Are

colin

eH

Cl

Aza

thio

prin

eB

enzi

dine

2H

Cl

2-B

iphe

nyla

min

eH

Cly

13-

But

adie

nez

Cap

tafo

lz C

arba

myl

hydr

azin

eH

Cl

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 1-

Chl

oro-

4-ni

trob

enze

ney

5-C

hlor

o-o-

tolu

idin

ey 4-

Chl

oro-

o-to

luid

ine

HC

ly p-

Chl

oroa

nilin

eH

Clz

Chl

orop

rene

z C

upfe

rron

z D

acar

bazi

nez

Dam

inoz

idez

24-

Dia

min

otol

uene

2H

Clz

12-

Dib

rom

oeth

anez

Dif

talo

ne7

12-

Dim

ethy

lben

z(a)

anth

race

ne1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylhy

draz

ine

HC

lG

lu-P

-1z

Glu

-P-2

z p-

Hyd

razi

nobe

nzoi

cac

idH

Cl

1-H

ydro

xysa

frol

ez Is

opre

neM

eA-a

-Cac

etat

ez N

-Met

hyl-

N-f

orm

ylhy

draz

ine

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

Mic

hler

rsquoske

tone

z 5-

Nitr

o-o-

tolu

idin

ey N

itro

fenz

N-N

itros

o-N

-met

hylu

reaz

Pent

achl

oroa

niso

lez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y2

34

56

-Pen

tach

loro

phen

olt

echn

ical

grad

ez n-

Pen

tylh

ydra

zine

HC

lPh

enyl

ethy

lhyd

razi

nesu

lfat

ePh

enyl

hydr

azin

eH

Cl

Ster

igm

atoc

ysti

nz Te

tra

uoro

ethy

lene

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)zo

-Tol

uidi

neH

Clz

24

6-T

rich

loro

anil

iney

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nili

neH

Clz

Ure

than

ez V

inyl

carb

amat

eV

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y 2

5-X

ylid

ine

HC

lz

Mon

key

2A

ato

xin

B1y

Ure

than

ez

Rat

32A

nilin

eH

Cly

Azo

benz

eney

Ben

zene

z C

livor

ine

Cup

ferr

onz

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neI

QH

Cl

Las

ioca

rpin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line)

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-N

itros

o-( 2

-hyd

roxy

prop

yl) -

( 2-h

ydro

xyet

hyl)

amin

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nitr

osob

is( 2

-oxo

prop

yl) a

min

eN

-Nit

roso

diet

hano

lam

ine

N-N

itro

sodi

ethy

lam

ine

N-N

itros

odim

ethy

lam

inez

N-N

itros

omet

hyl-

( 2-t

osyl

oxye

thyl

) am

ine

N-N

itros

omor

phol

ine

N-N

itro

sopy

rrol

idin

ez Pe

tasi

teni

neS

teri

gmat

ocys

tinz

Sym

phyt

ine

Tetr

auo

roet

hyle

nez

o-To

luid

ine

HC

lz T

rp-P

-2ac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

aT

here

was

nore

port

edta

rget

site

in1

spec

ies

( rat

sor

mic

e)fo

r5

chem

ical

sw

ithsu

pers

crip

tsb

utth

ech

emic

alw

asev

alua

ted

byth

epu

blis

hed

auth

oras

aca

rcin

ogen

ald

rinz

diel

drin

z N

-nit

roso

pyrr

olid

inez

23

45

6-pe

ntac

hlor

ophe

nol

( Dow

icid

eE

C-7

)ya

ndur

etha

nez

bN

asal

cavi

tyin

clud

estis

sues

ofth

eno

sen

asal

turb

inat

esp

aran

asal

sinu

ses

and

trac

hea

c Ora

lcav

ityin

clud

estis

sues

ofth

em

outh

oro

phar

ynx

phar

ynx

and

lary

nx

Ach

emic

alis

liste

dun

der

each

orga

nev

alua

ted

aspo

sitiv

ein

anex

peri

men

tin

that

spec

ies

byat

leas

t1au

thor

The

refo

rea

chem

ical

may

beli

sted

unde

rse

vera

ltar

geto

rgan

san

dev

ery

chem

ical

liste

din

the

tabl

eis

posi

tive

inat

leas

t1sp

ecie

sIn

orde

rto

com

pare

resu

ltsin

rats

and

mic

esy

mbo

lsfo

llow

chem

ical

ste

sted

inbo

thsp

ecie

sa

zin

dica

tes

that

the

chem

ical

ispo

sitiv

eat

som

esi

tein

both

spec

ies

and

ay

indi

cate

sth

atit

was

test

edin

both

butp

ositi

vein

only

1a

Nth

enu

mbe

rof

chem

ical

sw

ithat

leas

t1po

sitiv

ete

stat

that

site

inth

atsp

ecie

sB

ecau

sem

any

chem

ical

sin

duce

tum

ors

atm

ore

than

1si

tein

agi

ven

spec

ies

man

ych

emic

als

appe

arm

ore

than

once

inth

eta

ble

648

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649

species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters

RESULTS IN RATS AND MICE

For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens

TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database

Chemicals evaluated as carcinogenic in

Rats Mice

All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)

Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2

a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not

b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats

All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical

to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included

The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site

Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 5: Compendium of Chemical Carcinogens by Target Organ - Toxnet

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z Ph

enyl

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Pipe

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idy

N-N

-Pro

pyl-

N-f

orm

ylhy

draz

ine

Damp

Cre

dno

5z

Rif

ampi

ciny

Rip

azep

amy

p-R

osan

iline

HC

lz S

afro

lez

Sali

cyla

zosu

lfap

yrid

inez

Sel

eniu

mdi

ethy

ldith

ioca

rbam

ate

Sel

eniu

msu

lde

z S

trob

ane

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

11

12-

Tetr

achl

oroe

than

ey 1

12

2-Te

trac

hlor

oeth

aney

Tetr

achl

oroe

thyl

enez

Tetr

achl

orvi

npho

sy Te

tra

uoro

-m-p

heny

lene

diam

ine

2HC

ly Te

tra

uoro

ethy

lene

z Te

trah

ydro

fura

nz T

hioa

ceta

mid

ez 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

m-T

olui

dine

HC

ly o-

Tolu

idin

eH

Clz

p-To

luid

ine

HC

ly To

xaph

eney

T-2

toxi

nT

riam

tere

ney

Tri

chlo

roac

etic

acid

y 2

46-

Tri

chlo

roan

iline

y 1

12-

Tri

chlo

roet

hane

y T

rich

loro

ethy

lene

z T

rich

loro

ethy

lene

( wit

hout

epic

hlor

ohyd

rin)

y 2

46-

Tri

chlo

roph

enol

z 1

23-

Tri

chlo

ropr

opan

ez T

ri

ural

int

echn

ical

grad

ey 2

45-

Tri

met

hyla

nili

nez

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nilin

eH

Clz

24

6-T

rini

tro-

13-

dim

ethy

l-5-

tert

-but

ylbe

nzen

eT

ris(

2-ch

loro

ethy

l)ph

osph

atez

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez T

ris(

2-et

hylh

exyl

) pho

spha

tey

Trp

-P-1

acet

atez

Trp

-P-2

acet

atez

Ure

than

ez V

inyl

carb

amat

eV

inyl

uo

ride

z 2

5-X

ylid

ine

HC

lz C

Id

ispe

rse

yell

ow3z

Zea

rale

none

y

Mon

key

8A

ato

xin

B1y

Cyc

asin

and

met

hyla

zoxy

met

hano

lace

tate

IQ

z N

-Nitr

osod

ieth

ylam

ine

N-N

itro

sodi

prop

ylam

ine

N-N

itro

sopi

peri

dine

z S

teri

gmat

ocys

tinz

Ure

than

ez

Rat

206

Ace

tam

idez

Ace

tam

inop

henz

Ace

toxi

me

2-A

cety

lam

ino

uore

nez

A

atox

icol

A

atox

inB

y 1A

at

oxin

cru

dez

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

min

o-2-

met

hyla

nthr

aqui

none

z 2-

Am

inoa

nthr

aqui

none

z o-

Am

inoa

zoto

luen

ey 11

-Am

inou

ndec

anoi

cac

idy

Ara

mit

ez A

rocl

or12

60A

uram

ine-

Oz

Azo

xym

etha

neB

emit

radi

ne

Ben

zidi

ne3

-Ben

zyls

ydno

ne-4

-ace

tam

idez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

CI

dir

ectb

lue

15

Bro

mod

ichl

orom

etha

nez

Bud

eson

ide

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Chl

oren

dic

acid

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 2-

Chl

oro-

5-( 3

5-d

imet

hylp

iper

idin

osul

phon

yl) b

enzo

icac

id[

4-C

hlor

o-6-

( 23

-xy

lidi

no) -

2-py

rim

idin

ylth

io] a

ceti

cac

idz

4-C

hlor

o-6-

( 23

-xyl

idin

o)-2

-pyr

imid

inyl

thio

( N-b

-hyd

roxy

ethy

l)ac

etam

idez

Chl

orob

enze

ney

Chl

orof

orm

z 3-

( p-C

hlor

ophe

nyl)

-11

-dim

ethy

lure

ay C

ipro

bra

tez

Cliv

orin

eC

lob

rate

y C

loph

enA

30C

oum

arin

z p-

Cre

sidi

nez

Cro

tona

ldeh

yde

Cup

ferr

onz

Cyc

lope

ntan

one

oxim

eD

DT

z D

ecab

rom

odip

heny

loxi

dey

Deh

ydro

epia

ndro

ster

one

Deh

ydro

epia

ndro

ster

one

acet

ate

24-

Dia

min

otol

uene

z 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ibro

moe

than

ez D

ichl

oroa

ceti

cac

idz

Dic

hlor

oace

tyle

nez

NN

-Die

thyl

-4-(

4-[

pyri

dyl-

1-o

xide

] azo

) ani

line

Die

thyl

stil

best

rolz

Dim

etho

xane

3

3-D

imet

hoxy

benz

idin

e2H

Cl

56-

Dim

etho

xyst

erig

mat

ocys

tinN

N-D

imet

hyl-

4-am

inoa

zobe

nzen

e6-

Dim

ethy

lam

ino-

44-

diph

enyl

-3-h

epta

nola

ceta

teH

Cly

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hyln

itram

ine

Din

itros

ohom

opip

eraz

ine

26-

Din

itro

tolu

ene

24-

Din

itrot

olue

ne( c

onta

inin

g1

0-1

52

6-di

nitr

otol

uene

)z

Din

itrot

olue

net

echn

ical

grad

e( 2

4( 7

7) -

and

26

( 19

) -)

14-

Dio

xane

z D

ipen

tyln

itro

sam

ine

Dox

ylam

ine

succ

inat

ez E

thin

yles

trad

iol

Eth

ioni

ne

dl-E

thio

nine

z 4-

Eth

oxy-

phen

ylur

eaE

thyl

alco

holy

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neE

thyl

ene

thio

urea

z di

( 2-E

thyl

hexy

l)ph

thal

atez

Flu

cona

zole

y N

-(2-

Flu

oren

yl) -

22

2-tr

iuo

roac

etam

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

Fum

onis

inB

1F

uran

z Fu

rfur

alz

Glu

-P-1

z G

lu-P

-2z

FDamp

Cgr

een

no1

y H

CD

Dm

ixtu

rez

Hex

achl

orob

enze

nez

a-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

z H

ydra

zine

z H

ydra

zine

sulf

atez

Hyd

razo

benz

enez

Hyd

roch

loro

uor

ocar

bon

123

N-H

ydro

xy-2

-ace

tyla

min

ouo

rene

z 1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-nitr

oso-

3-ch

loro

ethy

lure

a1

-Hyd

roxy

safr

olez

IQz

IQH

Cl

Ison

iazi

dz K

epon

ez L

asio

carp

ine

MeA

-a-C

acet

atez

MeI

Qxz

Met

hapy

rile

neH

Cl

Z-M

ethy

l-O

NN

-azo

xyet

hane

Met

hylc

arba

mat

ey M

ethy

lclo

fena

pate

z 3

-Met

hyl-

4-di

met

hyla

min

oazo

benz

ene

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

4-( 4

-N-M

ethy

l-N

-nit

rosa

min

osty

ryl)

quin

olin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line

) 4

4-M

ethy

lene

dian

ilin

e2H

Clz

4-( M

ethy

lnit

rosa

min

o)-1

-(3-

pyri

dyl)

-1-(

buta

none

) M

etro

nida

zole

z M

ichl

errsquos

keto

nez

Mir

exz

Mon

ocro

tali

neN

afen

opin

Nit

rite

sod

ium

y N

itrob

enze

nez

2-N

itro

buta

ne2

-Nit

ro

uore

ne3

-Nit

rope

ntan

eN

-Nitr

oso-

bis-

( 44

4-t

ri

uoro

-N-b

utyl

) am

ine

1-N

itros

o-5

6-di

hydr

oura

cil

N-N

itro

so-2

3-d

ihyd

roxy

prop

ylet

hano

lam

ine

1-N

itros

o-1-

hydr

oxye

thyl

-3-c

hlor

oeth

ylur

ea1

-Nitr

oso-

1-( 2

-hyd

roxy

prop

yl) -

3-ch

loro

ethy

lure

aN

-Nitr

oso-

( 2-h

ydro

xypr

opyl

) -( 2

-hyd

roxy

ethy

l)am

ine

N-N

itros

o-N

-met

hyl-

N-d

odec

ylam

ine

Nit

roso

-N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

e

( Con

tinue

don

next

page

)

643

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

N-N

itro

so-N

-met

hyld

ecyl

amin

e3-

Nit

roso

-2-o

xazo

lidin

one

Nit

roso

-2-o

xopr

opyl

etha

nola

min

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osoa

llyl

etha

nola

min

eN

-Nit

roso

bis(

2-ox

opro

pyl)

amin

eN

itro

sodi

buty

lam

inez

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

imet

hyla

min

ez p-

Nitr

osod

iphe

nyla

min

ez N

-Nit

roso

dipr

opyl

amin

eN

itros

odod

ecam

ethy

lene

imin

eN

-Nit

roso

ephe

drin

eN

itro

soet

hylm

ethy

lam

ine

Nitr

osoh

epta

met

hyle

neim

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

met

hyl-

( 2-h

ydro

xyet

hyl)

amin

eN

-Nitr

osom

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

-Nitr

osom

ethy

l(2-

oxop

ropy

l)am

ine

N-N

itro

som

ethy

l-( 2

-tos

ylox

yeth

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eN

-Nit

roso

mor

phol

ine

N-N

itros

opip

erid

inez

N-N

itro

sopy

rrol

idin

ez N

-Nit

roso

thia

ldin

eo-

Nit

roso

tolu

ene

Nor

lest

rinz

N-(

9-O

xo-2

-uo

reny

l)ac

etam

ide

44

-Oxy

dian

iline

z 2

34

56-

Pent

achl

orop

heno

lte

chni

calg

rade

z P

etas

iten

ine

Phe

noba

rbit

als

odiu

mz

1-P

heny

lazo

-2-n

apht

holy

o-P

heny

lene

diam

ine

2HC

lz P

iper

onyl

buto

xide

z P

olyb

rom

inat

edbi

phen

ylm

ixtu

rez

Pre

dnis

olon

eP

yril

amin

em

alea

tey

CI

aci

dre

d11

4C

Ip

igm

entr

ed3z

Damp

Cre

dno

5z

Damp

Cre

dno

9y

FD

ampC

red

no1

p-

Ros

anili

neH

Clz

Saf

role

z Se

leni

umsu

lde

z Se

nkir

kine

Ste

rigm

atoc

ystin

z S

ymph

ytin

eTa

mox

ifen

citr

atez

Telo

neII

tec

hnic

algr

adez

33

44

-Te

traa

min

obip

heny

l4H

Clz

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

auo

roet

hyle

nez

Thi

oace

tam

idez

44

-Thi

odia

nilin

ez To

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

Tri

amci

nolo

neac

eton

ide

24

5-T

rim

ethy

lani

line

z 2

45-

Tri

met

hyla

nili

neH

Clz

24

6-T

rim

ethy

lani

line

HC

lz T

rini

trog

lyce

rin

Trp

-P-1

acet

atez

Trp

-P-2

acet

atez

Vin

ylac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

CI

dis

pers

eye

llow

3z

Tre

esh

rew

1A

ato

xin

B1y

Lun

gH

amst

er3

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

1-N

itro

so-3

45

-tri

met

hylp

iper

azin

eM

ouse

116

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-is

onic

otin

oylh

ydra

zine

A

llyl

hydr

azin

eH

Cl

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

Are

coli

neH

Cl

5-A

zacy

tidi

nez

Ben

zene

z B

enzo

fura

nz B

enzo

tric

hlor

ide

Ben

zoyl

hydr

azin

eB

enzy

lhyd

razi

ne2

HC

l2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 2-c

hlor

o-1-

met

hyle

thyl

) eth

er

tech

nica

lgra

dey

Bis

-(ch

loro

met

hyl)

ethe

rz 1

3-B

utad

iene

z N

-n-B

utyl

-N-f

orm

ylhy

draz

ine

But

ylat

edhy

drox

ytol

uene

y 1

1-di

-n-B

utyl

hydr

azin

en-

But

ylhy

draz

ine

HC

l1

2-di

-N-B

utyl

hydr

azin

e2H

Cl

Caf

feic

acid

z C

arba

myl

hydr

azin

eH

Cl

1-C

arba

myl

-2-p

heny

lhyd

razi

neC

hlor

ambu

cilz

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z C

oum

arin

z C

yclo

phos

pham

idez

Dac

arba

zine

z D

amin

ozid

ez p

p-D

DD

y D

DT

z 1

1-D

iall

ylhy

draz

ine

12-

Dia

llyl

hydr

azin

e2H

Cl

Dib

enz(

ah)

anth

race

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

Dib

rom

odul

cito

lz 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

12-

Dic

hlor

oeth

anez

12-

Dif

orm

ylhy

draz

ine

Dih

ydro

safr

olez

25-

Dim

etho

xy-4

-am

inos

tilbe

nez

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

a-E

cdys

one

Est

radi

olm

usta

rdy

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylen

eim

ine

Eth

ylen

eox

idez

Eth

ylhy

draz

ine

HC

l5-

Flu

orou

raci

ly Fo

rmyl

hydr

azin

eG

lyci

dolz

c-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

y H

exan

alm

ethy

lfor

myl

hydr

azon

eH

ydra

zine

z H

ydra

zine

sulf

atez

IQz

Isob

utyl

nitr

itez

Ison

iazi

dz Is

onic

otin

icac

idva

nilly

liden

ehyd

razi

de

Isop

rene

Lov

asta

tinM

eIQ

xz M

elph

alan

z 1-

Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m

N-M

ethy

l-N

-for

myl

hydr

azin

eM

ethy

lmet

hane

sulf

onat

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eM

ethy

lene

chlo

ride

z M

ethy

lhyd

razi

ne

Met

hylh

ydra

zine

sulf

ate

( N-6

) -( M

ethy

lnit

roso

) ade

nine

(N

-6) -

( Met

hyln

itro

so) a

deno

sine

N-M

ethy

lola

cryl

amid

ey M

etro

nida

zole

z M

olyb

denu

mtr

ioxi

dey

Mon

oace

tylh

ydra

zine

Nap

htha

lene

15

-Nap

htha

lene

diam

inez

Nic

otin

icac

idhy

draz

ide

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez 3-

Nitr

o-3-

hexe

nez

Nit

robe

nzen

ez N

itrom

etha

nez

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

dim

ethy

lam

inez

N-N

itros

ohex

amet

hyle

neim

ine

N-N

itro

sopi

peri

dine

z O

zone

y Pe

ntan

alm

ethy

lfor

myl

hydr

azon

en-

Pen

tylh

ydra

zine

HC

lPh

enes

teri

nz Ph

enyl

ethy

lhyd

razi

nesu

lfat

eP

roca

rbaz

ine

HC

lz N

-N-P

ropy

l-N

-for

myl

hydr

azin

eP

ropy

lhyd

razi

neH

Cl

Sel

eniu

msu

lde

z S

trep

tozo

toci

nz Su

lfal

late

z Te

lone

IIt

echn

ical

grad

ez 3

34

4-T

etra

amin

obip

heny

l4H

Clz

Tetr

anitr

omet

hane

z T-

2to

xin

Tri

chlo

roet

hyle

nez

Tri

ura

lint

echn

ical

grad

ey 2

45-

Tri

met

hyla

nilin

eH

Clz

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez U

reth

anez

Vin

ylch

lori

dez

Vin

ylu

orid

ez V

inyl

iden

ech

lori

dey

24-

Xyl

idin

eH

Cly

Mon

key

1U

reth

anez

Rat

551-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro

-2-f

uryl

) -1

34-

oxad

iazo

le2

-Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-5-

nitr

othi

azol

ey 1-

Am

yl-1

-nitr

osou

rea

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is-(

chlo

rom

ethy

l)et

herz

HC

blue

no1

z B

rom

oeth

anez

N-n

-But

yl-N

-nit

roso

urea

Cad

miu

mch

lori

deC

adm

ium

sulp

hate

( 11

) 1-

Chl

oroe

thyl

nitr

oso-

3-( 2

-hyd

roxy

prop

yl) u

rea

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z 1

2-D

ibro

moe

than

ez D

imet

hylh

ydro

gen

phos

phit

ey tr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-

[ 2-(

5-ni

tro-

2-fu

ryl)

viny

l] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

12-

Epo

xybu

tane

y 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

Hyd

razi

nez

Hyd

razi

nesu

lfat

ez 1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

Isob

utyl

nitr

itez

Ison

iazi

dz 4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4-

( Met

hyln

itros

amin

o)-1

-(3-

pyri

dyl)

-1-b

utan

ol4

-(M

ethy

lnit

rosa

min

o)-1

-(3-

pyri

dyl)

-1-(

buta

none

) N

-[ 3

-(5-

Nitr

o-2-

fury

l)-

12

4-ox

adia

zole

-5-y

l] -m

ethy

lace

tam

ide

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

3-N

itro-

3-he

xene

z 5-

Nitr

oace

naph

then

ez N

-Nit

roso

-bis

-(4

44-

tri

uoro

-N-b

utyl

) am

ine

N-N

itros

o-N

-met

hyl-

N-d

odec

ylam

ine

N-N

itros

o-N

-met

hyl-

N-t

etra

decy

lam

ine

N-N

itro

so-N

-met

hyld

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

lure

az N

-Nitr

osob

is( 2

-hyd

roxy

prop

yl)

amin

eN

-Nitr

osob

is-2

3-d

ihyd

roxy

prop

ylam

ine

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itros

odim

ethy

lam

inez

N-N

itro

soep

hedr

ine

Nitr

osoe

thyl

met

hyla

min

eN

-Nit

roso

met

hyl

N-N

itro

som

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eC

Ia

cid

red

114

Sod

ium

dich

rom

ate

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

anit

rom

etha

nez

24

5-T

rim

ethy

lani

line

z 2

46-

Tri

met

hyla

nili

neH

Clz

Vin

ylch

lori

dez

Mam

mar

ygl

and

Dog

1Ly

nest

reno

lH

amst

er1

Vin

ylch

lori

dez

Mou

se24

5-A

zacy

tidin

ez B

enze

nez

CI

dir

ectb

lack

381

3-B

utad

iene

z C

alci

fero

lC

hlor

opre

nez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Die

thyl

stilb

estr

olz

a-E

cdys

one

Est

radi

olE

thyl

ene

oxid

ez F

uros

emid

ey G

lyci

dolz

Gri

seof

ulvi

nIs

onia

zidz

Ison

icot

inic

acid

vani

llylid

eneh

ydra

zide

( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Nitr

oben

zene

z R

eser

pine

z Su

lfal

late

z V

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y

644

Rat

102

4-A

cety

lam

inob

iphe

nyl

2-A

cety

lam

ino

uore

nez

Acr

onyc

ine

Acr

ylam

ide

Acr

ylon

itri

leA

F-2

z 1-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro-

2-fu

ryl)

-13

4-

oxad

iazo

le2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

e2-

Am

ino-

5-ni

trot

hiaz

oley

4-A

min

odip

heny

lHC

l1-

Am

yl-1

-nit

roso

urea

Atr

azin

ey B

emit

radi

ne

Ben

zidi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

4-B

is( 2

-hyd

roxy

ethy

l)am

ino-

2-( 5

-nit

ro-2

-thi

enyl

) qui

nazo

line

13-

But

adie

nez

N-n

-But

yl-N

-nitr

osou

rea

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Car

boxy

met

hyln

itros

oure

aC

hlor

ambu

cilz

Chl

orop

rene

z C

ytem

bena

y D

acar

bazi

nez

N-1

-Dia

ceta

mid

ouo

rene

46

-Dia

min

o-2-

( 5-n

itro-

2-fu

ryl)

-S-t

riaz

ine

24-

Dia

min

oani

sole

sulf

atez

24-

Dia

min

otol

uene

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dib

rom

oman

nito

lz 1

3-D

ibut

yl-1

-nit

roso

urea

33

-Dic

hlor

oben

zidi

ne1

2-D

ichl

oroe

than

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

12-

Dim

ethy

l-5-

nitr

oim

idaz

ole

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lam

inoe

thyl

nitr

osoe

thyl

urea

nitr

ite

salt

33

-Dim

ethy

lben

zidi

ne2

HC

lz 2-

( 22

-Dim

ethy

lhyd

razi

no) -

4-( 5

-nitr

o-2-

fury

l)th

iazo

le

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

24-

Dio

xane

z 1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

6-di

nitr

otol

uene

)zN

-(2-

Fluo

reny

l)-2

22

-tri

uo

roac

etam

ide

Form

icac

id2-

( 4-m

ethy

l-2-

thia

zoly

l)hy

draz

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-

thia

zoly

l] hyd

razi

dez

Gly

cido

lz H

exam

ethy

lmel

amin

eN

-Hex

ylni

tros

oure

a2-

Hyd

razi

no-4

-(p-

amin

ophe

nyl)

thia

zole

z 2-

Hyd

razi

no-4

-( 5

-nit

ro-2

-fur

yl) t

hiaz

olez

2-H

ydra

zino

-4-(

p-ni

trop

heny

l)th

iazo

lez

Hyd

razo

benz

enez

1-( 2

-Hyd

roxy

ethy

l)-3

-[( 5

-nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

e1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

1-(

2-H

ydro

xyet

hyl)

-1-n

itros

oure

az In

dom

etha

cin

IQz

IQH

Cl

Ison

iazi

dz 2-

Met

hoxy

-3-a

min

odib

enzo

fura

n4-

Met

hyl-

1-[(

5-ni

trof

urfu

rylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

-(N

-Met

hyl-

N-n

itro

soca

rbam

oyl)

-l-o

rnit

hine

3-M

ethy

lcho

lant

hren

e4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line)

Met

hyle

nech

lori

dez

Met

roni

dazo

lez

l-5-

Mor

phol

inom

ethy

l-3-

[(5-

nitr

ofur

fury

lide

ne) a

min

o]-

2-ox

azol

idin

one

HC

lN

ithia

zide

z 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

3-( 5

-Nitr

o-2-

fury

l)-i

mid

azo(

12-

a)

pyri

dine

z 4-

( 5-N

itro-

2-fu

ryl)

thia

zole

N

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

ide

NN

-[6-

( 5-N

itro

-2-f

uryl

) -S-

tria

zine

-24

-diy

l] bis

acet

amid

e5-

Nitr

oace

naph

then

ez 1-

[(5-

Nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

itrom

etha

nez

1-N

itrop

yren

eN

orle

stri

nz O

chra

toxi

nA

z N

-(9-

Oxo

-2-

uore

nyl)

acet

amid

ePh

enac

etin

z Ph

enes

teri

nz Ph

IPH

Clz

Proc

arba

zine

HC

lz Pr

opan

esu

lton

e1

2-Pr

opyl

ene

oxid

ez St

yren

ey Su

lfal

late

z 4

4-S

ulfo

nylb

isac

etan

ilid

eTo

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uor

o-N

-[4-

( 5-n

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

idez

Trp

-P-2

acet

atez

Vin

ylch

lori

dez

FD

ampC

viol

etno

1y

Mes

ovar

ium

Rat

2Sa

lbut

amol

Ter

buta

line

Myo

card

ium

Mou

se2

Est

radi

olm

usta

rdy

Phen

este

rinz

Nas

alca

vity

bB

ush

baby

1N

-Nitr

osod

ieth

ylam

ine

Ham

ster

11A

ceta

ldeh

yde

Dia

llyln

itros

amin

eD

imet

hylc

arba

myl

chlo

ride

Hyd

razi

nez

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osom

ethy

l-2

3-di

hydr

oxyp

ropy

lam

ine

N-N

itros

omor

phol

ine

N-N

itros

onor

nico

tine

N-N

itros

opip

erid

inez

Mou

se6

Ally

lgly

cidy

leth

ery

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 1

2-D

ibro

moe

than

ez Fo

rmal

dehy

dez

N-N

itro

sohe

xam

ethy

lene

imin

e1

2-Pr

opyl

ene

oxid

ez

Rat

43A

ceta

ldeh

yde

Acr

ylon

itril

e1-

Azo

xypr

opan

eB

enze

nez

Bis

-(ch

loro

met

hyl)

ethe

rz p-

Cre

sidi

nez

Dia

llyln

itros

amin

e1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dim

ethy

lnitr

amin

eD

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

e1

4-D

ioxa

nez

12-

Epo

xybu

tane

y Z

-Eth

yl-O

NN

-azo

xyet

hane

E

thyl

benz

ene

Eth

ylni

tros

ocya

nam

ide

Form

alde

hyde

z H

exam

ethy

lpho

spho

ram

ide

Hyd

razi

nez

N-N

itro

so-N

-met

hyld

ecyl

amin

edi

( N-N

itro

so) -

perh

ydro

pyri

mid

ine

N-N

itros

o(2

22-

tri

uoro

ethy

l)et

hyla

min

e1-

Nitr

oso-

34

5-tr

imet

hylp

iper

azin

eN

-Nitr

osoa

llyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyle

than

olam

ine

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

dipr

opyl

amin

eN

itros

oeth

ylm

ethy

lam

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nitr

osom

ethy

l-( 2

-hyd

roxy

ethy

l)am

ine

N-N

itro

som

ethy

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

norn

icot

ine-

1-N

-oxi

de

N-N

itro

sopi

peri

dine

z P

hena

cetin

z Ph

enyl

glyc

idyl

ethe

r1

2-Pr

opyl

ene

oxid

ez V

inyl

acet

atez

Vin

ylch

lori

dez

Ner

vous

Mou

se3

13-

But

adie

nez

N-N

itros

odim

ethy

lam

inez

Pro

carb

azin

eH

Clz

syst

emR

at21

Acr

ylam

ide

Acr

ylon

itril

eB

rom

oeth

anez

Chl

oram

buci

lz 1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

eC

yclo

phos

pham

idez

1-E

thyl

-1-n

itros

oure

aE

thyl

eneo

xide

z 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

eaG

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

R(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

S(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

M

ethy

lnit

ram

ine

N-N

itros

o-N

-met

hylu

reaz

N-N

itros

odie

than

olam

ine

1-P

heny

l-3

3-di

met

hyltr

iaze

neP

roca

rbaz

ine

HC

lz P

ropa

nesu

ltone

Vin

ylch

lori

dez

Ora

lcav

ityc

Ham

ster

4A

ceta

ldeh

yde

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itros

omor

phol

ine

N-N

itro

sopi

peri

dine

z

Mou

se3

N-N

itros

ohex

amet

hyle

neim

ine

12

3-T

rich

loro

prop

anez

Vin

ylac

etat

ez

Rat

32A

cryl

amid

eA

cryl

onitr

ile

Ben

zene

z 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

CI

dir

ectb

lue

15C

Id

irec

tblu

e21

8z C

hlor

opre

nez

3-D

iazo

tyra

min

eH

Cl

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

eG

lyci

dolz

IQz

MeA

-a-C

acet

atez

N-N

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

hydr

oxyp

ropy

lam

ine

Nit

roso

-23

-dih

ydro

xypr

opyl

-2-

oxop

ropy

lam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

itro

soam

ylur

etha

nN

-Nitr

osod

ieth

ylam

ine

Nit

roso

ethy

lure

than

N

itros

ohep

tam

ethy

lene

imin

e1-

Nitr

osoh

ydan

toin

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

thia

ldin

eN

-Nitr

osot

hiom

orph

olin

eC

Ia

cid

red

114

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tolu

eney

12

3-T

rich

loro

prop

anez

Xyl

ene

mix

ture

( m-x

ylen

eo-

xyle

nep

-xyl

ene)

Ova

ryM

ouse

10B

enze

nez

13-

But

adie

nez

Die

thyl

stil

best

rolz

N-M

ethy

lola

cryl

amid

ey 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

5-N

itroa

cena

phth

enez

1-[(

5-N

itro

furf

uryl

iden

e)am

ino]

hyda

ntoi

nz P

heno

lpht

hale

inz

Tam

oxif

enci

trat

ez 4-

Vin

ylcy

cloh

exen

ePa

ncre

asH

amst

er3

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

itro

so-2

6-d

imet

hylm

orph

olin

eN

itro

so-2

-oxo

prop

ylet

hano

lam

ine

Mon

key

1U

reth

anez

Rat

222-

Am

ino-

5-ni

trop

heno

ly 1-

( Am

inom

ethy

l)cy

cloh

exan

eace

ticac

idA

zase

rine

But

ylbe

nzyl

phth

alat

ey C

hlor

endi

cac

idz

Cin

nam

ylan

thra

nila

tez

Clo

bra

tey

Dic

hlor

vosz

Eth

ylal

coho

ly H

ydro

chlo

ro

uoro

carb

on12

3IQ

HC

lM

alon

alde

hyde

sod

ium

saltz

MeA

-a-C

acet

atez

2-M

erca

ptob

enzo

thia

zole

y M

ethy

lclo

fena

pate

z N

-(N

-Met

hyl-

N-n

itros

ocar

bam

oyl)

-l-o

rnit

hine

4-(

Met

hyln

itro

sam

ino)

-1-(

3-py

ridy

l)-1

-but

anol

4-(

Met

hyln

itros

amin

o)-1

-( 3

-pyr

idyl

) -1-

( but

anon

e)N

afen

opin

Nitr

ofen

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)z1

23

-Tri

chlo

ropr

opan

ez

Peri

tone

alM

ouse

8B

is-1

2-(

chlo

rom

etho

xy) e

than

eB

is-1

4-(

chlo

rom

etho

xy) -

p-xy

lene

Bis

-(ch

loro

met

hyl)

ethe

rz C

hlor

opre

nez

tran

s-1

4-D

ichl

orob

uten

e-2

cavi

tyD

imet

hylc

arba

myl

chlo

ride

Phe

noxy

benz

amin

eH

Clz

Tri

s-1

23-

( chl

orom

etho

xy) p

ropa

neR

at22

Acr

onyc

ine

Acr

ylam

ide

Act

inom

ycin

DA

nili

neH

Cly

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

rom

ate

pota

ssiu

mz

Chl

oroz

otoc

in

Cyt

embe

nay

Dap

sone

y 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

4-D

ioxa

nez

Eth

ylen

eox

idez

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz M

elph

alan

z N

-Met

hyl-

N4

-din

itros

oani

line

Mit

omyc

in-C

N-N

itro

so-2

24

-tri

met

hyl-

12-

dihy

droq

uino

line

poly

mer

Ph

enox

yben

zam

ine

HC

lz o-

Tolu

idin

eH

Clz

( Con

tinue

don

next

page

)

645

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Pitu

itar

ygl

and

Mou

se8

Die

thyl

stil

best

rolz

Eno

vid

Eth

ylen

eth

iour

eaz

Iodi

nate

dgl

ycer

olz

Isop

rene

Nor

lest

rinz

Pro

pylt

hiou

raci

lz Z

eara

leno

ney

Rat

73-

Am

inot

riaz

olez

12-

Dib

rom

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylal

coho

ly 2-

Mer

capt

oben

zoth

iazo

ley

Met

roni

dazo

lez

Nor

lest

rinz

Pros

tate

Rat

4C

adm

ium

chlo

ride

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

PhIP

HC

lz

Skin

Ham

ster

2U

reth

anez

Vin

ylch

lori

dez

Mou

se5

5-A

zacy

tidin

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Chl

orop

rene

z G

lyci

dolz

Thi

o-te

paz

Rat

332-

Ace

tyla

min

ouo

rene

z 3-

Am

ino-

9-et

hylc

arba

zole

mix

ture

z 1-

Azo

xypr

opan

e2-

Azo

xypr

opan

eB

enze

nez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

ol

tech

nica

lgra

dez

CI

dir

ectb

lue

15C

arbo

xym

ethy

lnitr

osou

rea

24-

Dia

min

oani

sole

sulf

atez

Dib

rom

odul

cito

lz D

ibro

mom

anni

tolz

Dim

etho

xane

2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

Dim

ethy

lvin

ylch

lori

dez

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

26-

dini

trot

olue

ne)z

1-E

thyl

nitr

oso-

3-( 2

-hyd

roxy

ethy

l)-u

rea

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz 1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

IQ

z L

asio

carp

ine

MeI

Qxz

N-(

N-M

ethy

l-N

-nitr

osoc

arba

moy

l)-l

-orn

ithi

ne

5-N

itro-

o-an

isid

inez

CI

aci

dre

d11

4p-

Ros

anili

neH

Clz

Thi

o-te

paz

Thi

oure

ay V

inyl

chlo

ride

z F

Damp

Cvi

olet

no1

y

Smal

lint

esti

neM

ouse

6C

apta

folz

Cap

tanz

N-E

thyl

-N-n

itro

-N-n

itro

sogu

anid

ine

Hyd

roge

npe

roxi

deN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-(

Tri

chlo

rom

ethy

lthi

o)ph

thal

imid

eM

onke

y1

Ure

than

ez

Rat

29A

cryl

onitr

ile

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is( 2

3-d

ibro

mop

ropy

l)ph

osph

ate

mag

nesi

umsa

lt4

-Bis

( 2-h

ydro

xyet

hyl)

amin

o-2-

( 5-n

itro

-2-t

hien

yl) q

uina

zolin

eC

Id

irec

tblu

e15

Car

boxy

met

hyln

itros

oure

a1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

e2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro

-2-f

uryl

)py

rim

idin

etr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-[

2-( 5

-nit

ro-2

-fur

yl) v

inyl

] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

Z-E

thyl

-ON

N-a

zoxy

met

hane

1-E

thyl

-1-n

itros

oure

aFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lu-P

-1z

Glu

-P-2

z IQ

z L

asio

carp

ine

N-M

ethy

l-N

-nitr

o-N

-nitr

osog

uani

dine

z N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez N

-Nitr

oso-

N-i

sobu

tylu

rea

3-N

itro

so-2

-oxa

zoli

dino

neN

itro

soet

hylu

reth

ane

PhI

PH

Clz

Pro

pane

sulto

neQ

uerc

etin

y C

Ia

cid

red

114

Trp

-P-2

acet

atez

Sple

enR

at7

Ani

line

HC

ly A

zobe

nzen

ey p-

Chl

oroa

nili

neH

Clz

Dap

sone

y o-

Nitr

osot

olue

neD

ampC

red

no9

y o-

Tolu

idin

eH

Clz

Stom

ach

Ham

ster

18A

F-2z

14-

Din

itros

o-2

6-di

met

hylp

iper

azin

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z H

ydra

zine

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] a

ceta

mid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

N-N

itro

so-2

3-d

ihyd

roxy

prop

yl-2

-hyd

roxy

prop

ylam

ine

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

-Nitr

oso-

ethy

l-2-

oxop

ropy

lure

aN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

itros

o-5-

met

hylo

xazo

lidon

eN

-Nit

roso

-N-m

ethy

lure

than

N-N

itros

o-1

3-ox

azol

idin

eN

-Nit

roso

-2-p

heny

leth

ylur

ea1

-Nit

roso

-34

5-t

rim

ethy

lpip

eraz

ine

Ure

than

ez V

inyl

chlo

ride

z

Mou

se63

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eA

ciu

orfe

nA

F-2

z 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

tran

s-5-

Am

ino-

3[2-

( 5-n

itro-

2-fu

ryl)

viny

l] -1

24-

oxad

iazo

leA

reco

line

HC

lB

enza

ldeh

ydey

Ben

zofu

ranz

Ben

zotr

ichl

orid

eB

enzy

lace

tate

y B

enzy

lchl

orid

ey B

rom

oeth

anol

13

-But

adie

nez

But

ylat

edhy

drox

yani

sole

z 1

1-di

-N-B

utyl

hydr

azin

eC

affe

icac

idz

Cap

tafo

lz C

arba

zole

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z3

-(C

hlor

omet

hyl)

pyri

dine

HC

lz C

hlor

opre

nez

2-C

hlor

opro

pana

l1-

Chl

orop

rope

neC

ypro

tero

neac

etat

e1

1-D

ially

lhyd

razi

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dic

hlor

vosz

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez D

imet

hylv

inyl

chlo

ride

z D

init

roso

pipe

razi

neE

stra

diol

mus

tard

y E

thyl

acry

late

z Fo

rmic

acid

2-[ 4

-( 5

-nit

ro-2

-fur

yl) -

2-th

iazo

lyl] h

ydra

zide

z G

lyci

dolz

2-H

ydra

zino

-4-(

5-ni

tro-

2-fu

ryl)

thia

zole

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

ICI

1628

46z

IQz

Isop

rene

Lov

asta

tin

MeI

Q1

-Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m3

-(5-

Nitr

o-2-

fury

l)-

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] f

orm

amid

ez N

-Nit

roso

-N

-met

hylu

reaz

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

hexa

met

hyle

neim

ine

N-N

itros

opip

erid

inez

b-P

ropi

olac

tone

z Se

sam

olz

Sty

rene

oxid

ez Te

lone

IIt

echn

ical

grad

ez N

-(T

rich

loro

met

hylth

io) p

htha

limid

e1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uo

ro-N

-[4-

( 5-n

itro

-2-f

uryl

) -2-

thia

zoly

l]ac

etam

idez

Tri

ur

alin

tec

hnic

algr

adey

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylac

etat

ez

Rat

85A

ceto

ne[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zone

1-A

ceto

xysa

frol

ey A

cryl

onitr

ile

1-A

llyl

-1-n

itro

sour

ea2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-ox

adia

zole

2-

Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-4-

( 5-n

itro

-2-f

uryl

) thi

azol

ez 1-

Am

yl-1

-nit

roso

urea

Ari

stol

ochi

cac

id

sodi

umsa

lt( 7

7A

AI

21

AA

II)

Ben

zene

z B

enzo

( a) p

yren

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

BL

-634

1H

Cl

N-n

-But

yl-N

-nitr

osou

rea

But

ylat

edhy

drox

yani

sole

z b

-But

yrol

acto

neC

affe

icac

idz

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z4

-Chl

oro-

o-ph

enyl

ened

iam

inez

Chl

oro

uoro

met

hane

3-

( Chl

orom

ethy

l)py

ridi

neH

Clz

Cip

rob

rate

z C

upfe

rron

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez 2

5-D

imet

hoxy

-4-a

min

osti

lben

ez D

imet

hylh

ydro

gen

phos

phit

ey 4

6-D

imet

hyl-

2-( 5

-nit

ro-2

-fu

ryl)

pyri

mid

ine

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lvin

ylch

lori

dez

Epi

chlo

rohy

drin

y E

thyl

acry

late

z E

thyl

ene

oxid

ez 2-

Flu

oroe

thyl

-nitr

osou

rea

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-

nitr

osou

reaz

1-( 3

-Hyd

roxy

prop

yl) -

1-ni

tros

oure

a1

-Hyd

roxy

safr

olez

ICI

1628

46z

Lox

tidin

eL

upit

idin

e3H

Cl

Mer

curi

cch

lori

dey

3-M

etho

xyca

tech

ol4

-Met

hoxy

phen

olN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-M

ethy

l-N

-nit

roso

benz

amid

e4-

Met

hylc

atec

hol

Met

hyln

itro

socy

anam

ide

3-( 5

-Nit

ro-2

-fur

yl) -

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

4-( 5

-Nit

ro-2

-fur

yl) t

hiaz

ole

2-N

itro

uo

rene

8-N

itro

quin

olin

eN

itro

so-B

aygo

nN

-Nit

roso

-23

-dih

ydro

xypr

opyl

-2-h

ydro

xypr

opyl

amin

eN

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

oxop

ropy

lam

ine

1-N

itro

so-3

5-d

imet

hyl-

4-be

nzoy

lpip

eraz

ine

N-N

itro

so-N

-met

hyl-

N-d

odec

ylam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itro

so-N

-met

hylu

reaz

Nit

roso

-12

36

-tet

rahy

drop

yrid

ine

N-N

itro

sobe

nzth

iazu

ron

Nitr

osod

ibut

ylam

inez

N-N

itros

odie

thyl

amin

eN

-Nit

roso

ephe

drin

eN

itros

oeth

ylur

etha

nO

mep

razo

ley

Phen

acet

inz

Piv

alol

acto

ney

b-P

ropi

olac

tone

z N

-Pro

pyl-

N-n

itro

-N-n

itro

sogu

anid

ine

12-

Pro

pyle

neox

idez

Ses

amol

z St

yren

eox

idez

Sulf

alla

tez

Telo

neII

tec

hnic

algr

adez

12

3-T

rich

loro

prop

anez

24

6-T

rim

ethy

lani

line

HC

lz

646

Subc

utan

eous

Mou

se4

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

2-D

ibro

moe

than

ez N

2-c

-Glu

tam

yl-p

-hyd

razi

nobe

nzoi

cac

idG

lyci

dolz

tissu

eR

at13

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ichl

oroe

than

ez D

imet

hoxa

ne1

4-D

ioxa

nez

MeA

-a-C

acet

atez

44

-Met

hyle

ne-b

is( 2

-met

hyla

nili

ne)

o-N

itro

soto

luen

ep-

Ros

anili

neH

Clz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 2

45-

Tri

met

hyla

nilin

eH

Clz

25-

Xyl

idin

eH

Clz

Test

isM

ouse

4D

ieth

ylst

ilbe

stro

lz Fi

nast

erid

eR

eser

pine

z Ta

mox

ifen

citr

atez

Rat

185-

Aza

cytid

inez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

3-B

utad

iene

z N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

Cad

miu

mch

lori

de

2-C

hlor

o-1

11-

tri

uoro

etha

ne1

1-D

ichl

oro-

1-u

oroe

than

eH

ydro

chlo

rou

oroc

arbo

n12

3M

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z M

etro

nida

zole

z N

-Nit

roso

dim

ethy

lam

inez

Oxo

linic

acid

y SD

Z20

0-11

01

11

2-Te

tra

uoro

etha

ney

Tri

chlo

roet

hyle

nez

Tri

nitr

ogly

ceri

nV

inyl

chlo

ride

z

Thy

roid

glan

dH

amst

er4

Hex

achl

orob

enze

nez

Hyd

razi

nez

Met

hylt

hiou

raci

lU

reth

anez

Mou

se18

3-A

min

o-4-

etho

xyac

etan

ilide

y H

Cbl

ueno

1z

tert

-But

ylal

coho

lz C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

24

-Dia

min

oani

sole

sulf

atez

Die

thyl

stil

best

rolz

Dox

ylam

ine

succ

inat

ez E

thio

nam

idey

Eth

ylen

eth

iour

eaz

44

-Met

hyle

nedi

anil

ine

2HC

lz 1

5-N

apht

hale

nedi

amin

ez N

itrob

enze

nez

Oxa

zepa

my

44

-Oxy

dian

iline

z C

Ip

igm

entr

ed3z

Sulf

amet

hazi

ne2

37

8-T

etra

chlo

rodi

benz

o-p-

diox

inz

44

-Thi

odia

nilin

ez

Rat

33A

cryl

amid

e3-

Am

inot

riaz

olez

o-A

nisi

dine

HC

lz B

emit

radi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

Chl

orop

rene

z 2

4-D

iam

inoa

niso

lesu

lfat

ez N

N-D

ieth

ylth

iour

eay

1-E

thyl

-1-n

itro

sour

ea

Eth

ylen

eth

iour

eaz

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Flu

vast

atin

Gly

cido

lz Io

dina

ted

glyc

erol

z Is

obut

eney

Mal

onal

dehy

des

odiu

msa

ltz

Met

him

azol

e4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Mir

exp

hoto

-N

itro

benz

enez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

44

-Oxy

dian

iline

z Pr

opyl

thio

urac

ilz p-

Ros

anil

ine

HC

lz 2

37

8-Te

trac

hlor

odib

enzo

-p-d

ioxi

nz 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tri

met

hylt

hiou

reay

Vin

ylac

etat

ez Z

inc

dim

ethy

ldith

ioca

rbam

atez

Uri

nary

blad

der

Dog

23

3-D

ichl

orob

enzi

dine

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nilin

e)H

amst

er3

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

acet

amid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

Mou

se12

2-A

cety

lam

ino

uore

nez

4-A

min

odip

heny

l2-

Am

inod

iphe

nyle

neox

ide

o-A

nisi

dine

HC

lz 4-

Chl

oro-

4-a

min

odip

heny

leth

erz

p-C

resi

dine

z 4-

Eth

ylsu

lpho

nyln

apht

hale

ne-1

-sul

fona

mid

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hena

cetin

z Te

lone

IIt

echn

ical

grad

ez U

raci

lz

Mon

key

12-

Nap

hthy

lam

inez

Rat

49A

ceta

min

ophe

nz A

llyli

soth

iocy

anat

ey 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

4-A

min

o-2-

nitr

ophe

noly

11-A

min

ound

ecan

oic

acid

y o-

Ani

sidi

neH

Clz

Ari

stol

ochi

cac

ids

odiu

msa

lt( 7

7A

AI

21

AA

II)

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

ispe

rse

blue

1y N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

4-C

hlor

o-o-

phen

ylen

edia

min

ez m

-Cre

sidi

ney

p-C

resi

dine

z C

yclo

phos

pham

idez

Die

thyl

ene

glyc

olD

imet

hyla

rsin

icac

idy

Fose

tylA

lIQ

HC

lM

eA-a

-Cac

etat

ez M

elam

iney

2-M

etho

xy-3

-am

inod

iben

zofu

ran

2-N

apht

hyla

min

ez N

itril

otri

acet

icac

idz

Nitr

ilot

riac

etic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez o-

Nitr

oani

sole

z N

-Nitr

oso-

N-m

ethy

l-N

-dod

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

l-N

-tet

rade

cyla

min

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itro

sodi

phen

ylam

iney

o-N

itros

otol

uene

N-O

xydi

ethy

lene

thio

carb

amyl

-N-o

xydi

ethy

lene

sulf

enam

ide

Phe

nace

tinz

Phen

azon

eo-

Phen

ylph

enat

eso

dium

y o-

Phen

ylph

enol

y P

otas

sium

bica

rbon

ate

Purp

urin

Que

rcet

iny

p-Q

uino

nedi

oxim

ey Sa

ccha

rin

sodi

umy

Sali

cyla

zosu

lfap

yrid

inez

o-To

luen

esul

fona

mid

eo-

Tolu

idin

eH

Clz

Trp

-P-2

acet

atez

Ura

cilz

Ute

rus

Ham

ster

1N

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aM

ouse

12B

rom

oeth

anez

Chl

oroe

than

ey D

acar

bazi

nez

12-

Dic

hlor

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylen

eox

idez

Gly

cido

lz ( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Proc

arba

zine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez T

rim

ethy

lpho

spha

tey

Vin

ylac

etat

ez

Rat

26A

cryl

amid

e1-

Ally

l-1-

nitr

osou

rea

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

myl

-1-n

itros

oure

aA

traz

iney

CI

dir

ectb

lue

15B

rom

ocri

ptin

em

esyl

atey

N-n

-But

yl-N

-nit

roso

urea

Cal

cium

valp

roat

eC

apta

nz 2-

Chl

oro-

11

1-tr

iuo

roet

hane

Dac

arba

zine

z D

amin

ozid

ez 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

lD

imet

hyla

min

oeth

ylni

tros

oeth

ylur

ean

itri

tesa

lt1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

ICR

F-1

59z

Isop

hosp

ham

idez

15-

Nap

htha

lene

diam

inez

Nit

robe

nzen

ez N

orle

stri

nz 4

4-T

hiod

iani

linez

Vin

ylac

etat

ez

Vag

ina

Mou

se1

AZ

Tz

Rat

2A

ZT

z N

-n-B

utyl

-N-n

itro

sour

ea( C

ontin

ued

onne

xtpa

ge)

647

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Vas

cula

rsy

stem

Ham

ster

91

2-D

imet

hylh

ydra

zine

2H

Cl

Gly

cido

lz H

exac

hlor

oben

zene

z N

-Nit

roso

-eth

yl-2

-oxo

prop

ylur

eaN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

-Nitr

oso-

oxop

ropy

lchl

oroe

thyl

urea

N-N

itro

so-o

xopr

opyl

urea

N-N

itros

o-2-

phen

ylet

hylu

rea

Vin

ylch

lori

dez

Mou

se59

A-a

-CN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-ph

enyl

hydr

azin

eA

llyl

hydr

azin

eH

Cl

Are

colin

eH

Cl

Aza

thio

prin

eB

enzi

dine

2H

Cl

2-B

iphe

nyla

min

eH

Cly

13-

But

adie

nez

Cap

tafo

lz C

arba

myl

hydr

azin

eH

Cl

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 1-

Chl

oro-

4-ni

trob

enze

ney

5-C

hlor

o-o-

tolu

idin

ey 4-

Chl

oro-

o-to

luid

ine

HC

ly p-

Chl

oroa

nilin

eH

Clz

Chl

orop

rene

z C

upfe

rron

z D

acar

bazi

nez

Dam

inoz

idez

24-

Dia

min

otol

uene

2H

Clz

12-

Dib

rom

oeth

anez

Dif

talo

ne7

12-

Dim

ethy

lben

z(a)

anth

race

ne1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylhy

draz

ine

HC

lG

lu-P

-1z

Glu

-P-2

z p-

Hyd

razi

nobe

nzoi

cac

idH

Cl

1-H

ydro

xysa

frol

ez Is

opre

neM

eA-a

-Cac

etat

ez N

-Met

hyl-

N-f

orm

ylhy

draz

ine

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

Mic

hler

rsquoske

tone

z 5-

Nitr

o-o-

tolu

idin

ey N

itro

fenz

N-N

itros

o-N

-met

hylu

reaz

Pent

achl

oroa

niso

lez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y2

34

56

-Pen

tach

loro

phen

olt

echn

ical

grad

ez n-

Pen

tylh

ydra

zine

HC

lPh

enyl

ethy

lhyd

razi

nesu

lfat

ePh

enyl

hydr

azin

eH

Cl

Ster

igm

atoc

ysti

nz Te

tra

uoro

ethy

lene

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)zo

-Tol

uidi

neH

Clz

24

6-T

rich

loro

anil

iney

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nili

neH

Clz

Ure

than

ez V

inyl

carb

amat

eV

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y 2

5-X

ylid

ine

HC

lz

Mon

key

2A

ato

xin

B1y

Ure

than

ez

Rat

32A

nilin

eH

Cly

Azo

benz

eney

Ben

zene

z C

livor

ine

Cup

ferr

onz

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neI

QH

Cl

Las

ioca

rpin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line)

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-N

itros

o-( 2

-hyd

roxy

prop

yl) -

( 2-h

ydro

xyet

hyl)

amin

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nitr

osob

is( 2

-oxo

prop

yl) a

min

eN

-Nit

roso

diet

hano

lam

ine

N-N

itro

sodi

ethy

lam

ine

N-N

itros

odim

ethy

lam

inez

N-N

itros

omet

hyl-

( 2-t

osyl

oxye

thyl

) am

ine

N-N

itros

omor

phol

ine

N-N

itro

sopy

rrol

idin

ez Pe

tasi

teni

neS

teri

gmat

ocys

tinz

Sym

phyt

ine

Tetr

auo

roet

hyle

nez

o-To

luid

ine

HC

lz T

rp-P

-2ac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

aT

here

was

nore

port

edta

rget

site

in1

spec

ies

( rat

sor

mic

e)fo

r5

chem

ical

sw

ithsu

pers

crip

tsb

utth

ech

emic

alw

asev

alua

ted

byth

epu

blis

hed

auth

oras

aca

rcin

ogen

ald

rinz

diel

drin

z N

-nit

roso

pyrr

olid

inez

23

45

6-pe

ntac

hlor

ophe

nol

( Dow

icid

eE

C-7

)ya

ndur

etha

nez

bN

asal

cavi

tyin

clud

estis

sues

ofth

eno

sen

asal

turb

inat

esp

aran

asal

sinu

ses

and

trac

hea

c Ora

lcav

ityin

clud

estis

sues

ofth

em

outh

oro

phar

ynx

phar

ynx

and

lary

nx

Ach

emic

alis

liste

dun

der

each

orga

nev

alua

ted

aspo

sitiv

ein

anex

peri

men

tin

that

spec

ies

byat

leas

t1au

thor

The

refo

rea

chem

ical

may

beli

sted

unde

rse

vera

ltar

geto

rgan

san

dev

ery

chem

ical

liste

din

the

tabl

eis

posi

tive

inat

leas

t1sp

ecie

sIn

orde

rto

com

pare

resu

ltsin

rats

and

mic

esy

mbo

lsfo

llow

chem

ical

ste

sted

inbo

thsp

ecie

sa

zin

dica

tes

that

the

chem

ical

ispo

sitiv

eat

som

esi

tein

both

spec

ies

and

ay

indi

cate

sth

atit

was

test

edin

both

butp

ositi

vein

only

1a

Nth

enu

mbe

rof

chem

ical

sw

ithat

leas

t1po

sitiv

ete

stat

that

site

inth

atsp

ecie

sB

ecau

sem

any

chem

ical

sin

duce

tum

ors

atm

ore

than

1si

tein

agi

ven

spec

ies

man

ych

emic

als

appe

arm

ore

than

once

inth

eta

ble

648

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649

species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters

RESULTS IN RATS AND MICE

For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens

TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database

Chemicals evaluated as carcinogenic in

Rats Mice

All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)

Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2

a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not

b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats

All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical

to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included

The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site

Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 6: Compendium of Chemical Carcinogens by Target Organ - Toxnet

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

N-N

itro

so-N

-met

hyld

ecyl

amin

e3-

Nit

roso

-2-o

xazo

lidin

one

Nit

roso

-2-o

xopr

opyl

etha

nola

min

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osoa

llyl

etha

nola

min

eN

-Nit

roso

bis(

2-ox

opro

pyl)

amin

eN

itro

sodi

buty

lam

inez

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

diet

hyla

min

eN

-Nitr

osod

imet

hyla

min

ez p-

Nitr

osod

iphe

nyla

min

ez N

-Nit

roso

dipr

opyl

amin

eN

itros

odod

ecam

ethy

lene

imin

eN

-Nit

roso

ephe

drin

eN

itro

soet

hylm

ethy

lam

ine

Nitr

osoh

epta

met

hyle

neim

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

met

hyl-

( 2-h

ydro

xyet

hyl)

amin

eN

-Nitr

osom

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

-Nitr

osom

ethy

l(2-

oxop

ropy

l)am

ine

N-N

itro

som

ethy

l-( 2

-tos

ylox

yeth

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eN

-Nit

roso

mor

phol

ine

N-N

itros

opip

erid

inez

N-N

itro

sopy

rrol

idin

ez N

-Nit

roso

thia

ldin

eo-

Nit

roso

tolu

ene

Nor

lest

rinz

N-(

9-O

xo-2

-uo

reny

l)ac

etam

ide

44

-Oxy

dian

iline

z 2

34

56-

Pent

achl

orop

heno

lte

chni

calg

rade

z P

etas

iten

ine

Phe

noba

rbit

als

odiu

mz

1-P

heny

lazo

-2-n

apht

holy

o-P

heny

lene

diam

ine

2HC

lz P

iper

onyl

buto

xide

z P

olyb

rom

inat

edbi

phen

ylm

ixtu

rez

Pre

dnis

olon

eP

yril

amin

em

alea

tey

CI

aci

dre

d11

4C

Ip

igm

entr

ed3z

Damp

Cre

dno

5z

Damp

Cre

dno

9y

FD

ampC

red

no1

p-

Ros

anili

neH

Clz

Saf

role

z Se

leni

umsu

lde

z Se

nkir

kine

Ste

rigm

atoc

ystin

z S

ymph

ytin

eTa

mox

ifen

citr

atez

Telo

neII

tec

hnic

algr

adez

33

44

-Te

traa

min

obip

heny

l4H

Clz

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

auo

roet

hyle

nez

Thi

oace

tam

idez

44

-Thi

odia

nilin

ez To

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

Tri

amci

nolo

neac

eton

ide

24

5-T

rim

ethy

lani

line

z 2

45-

Tri

met

hyla

nili

neH

Clz

24

6-T

rim

ethy

lani

line

HC

lz T

rini

trog

lyce

rin

Trp

-P-1

acet

atez

Trp

-P-2

acet

atez

Vin

ylac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

CI

dis

pers

eye

llow

3z

Tre

esh

rew

1A

ato

xin

B1y

Lun

gH

amst

er3

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

1-N

itro

so-3

45

-tri

met

hylp

iper

azin

eM

ouse

116

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-is

onic

otin

oylh

ydra

zine

A

llyl

hydr

azin

eH

Cl

1-A

min

o-2

4-di

brom

oant

hraq

uino

nez

Are

coli

neH

Cl

5-A

zacy

tidi

nez

Ben

zene

z B

enzo

fura

nz B

enzo

tric

hlor

ide

Ben

zoyl

hydr

azin

eB

enzy

lhyd

razi

ne2

HC

l2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 2-c

hlor

o-1-

met

hyle

thyl

) eth

er

tech

nica

lgra

dey

Bis

-(ch

loro

met

hyl)

ethe

rz 1

3-B

utad

iene

z N

-n-B

utyl

-N-f

orm

ylhy

draz

ine

But

ylat

edhy

drox

ytol

uene

y 1

1-di

-n-B

utyl

hydr

azin

en-

But

ylhy

draz

ine

HC

l1

2-di

-N-B

utyl

hydr

azin

e2H

Cl

Caf

feic

acid

z C

arba

myl

hydr

azin

eH

Cl

1-C

arba

myl

-2-p

heny

lhyd

razi

neC

hlor

ambu

cilz

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z C

oum

arin

z C

yclo

phos

pham

idez

Dac

arba

zine

z D

amin

ozid

ez p

p-D

DD

y D

DT

z 1

1-D

iall

ylhy

draz

ine

12-

Dia

llyl

hydr

azin

e2H

Cl

Dib

enz(

ah)

anth

race

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

Dib

rom

odul

cito

lz 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

12-

Dic

hlor

oeth

anez

12-

Dif

orm

ylhy

draz

ine

Dih

ydro

safr

olez

25-

Dim

etho

xy-4

-am

inos

tilbe

nez

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

a-E

cdys

one

Est

radi

olm

usta

rdy

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylen

eim

ine

Eth

ylen

eox

idez

Eth

ylhy

draz

ine

HC

l5-

Flu

orou

raci

ly Fo

rmyl

hydr

azin

eG

lyci

dolz

c-1

23

45

6-H

exac

hlor

ocyc

lohe

xane

y H

exan

alm

ethy

lfor

myl

hydr

azon

eH

ydra

zine

z H

ydra

zine

sulf

atez

IQz

Isob

utyl

nitr

itez

Ison

iazi

dz Is

onic

otin

icac

idva

nilly

liden

ehyd

razi

de

Isop

rene

Lov

asta

tinM

eIQ

xz M

elph

alan

z 1-

Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m

N-M

ethy

l-N

-for

myl

hydr

azin

eM

ethy

lmet

hane

sulf

onat

e3-

Met

hylb

utan

alm

ethy

lfor

myl

hydr

azon

eM

ethy

lene

chlo

ride

z M

ethy

lhyd

razi

ne

Met

hylh

ydra

zine

sulf

ate

( N-6

) -( M

ethy

lnit

roso

) ade

nine

(N

-6) -

( Met

hyln

itro

so) a

deno

sine

N-M

ethy

lola

cryl

amid

ey M

etro

nida

zole

z M

olyb

denu

mtr

ioxi

dey

Mon

oace

tylh

ydra

zine

Nap

htha

lene

15

-Nap

htha

lene

diam

inez

Nic

otin

icac

idhy

draz

ide

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez 3-

Nitr

o-3-

hexe

nez

Nit

robe

nzen

ez N

itrom

etha

nez

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

dim

ethy

lam

inez

N-N

itros

ohex

amet

hyle

neim

ine

N-N

itro

sopi

peri

dine

z O

zone

y Pe

ntan

alm

ethy

lfor

myl

hydr

azon

en-

Pen

tylh

ydra

zine

HC

lPh

enes

teri

nz Ph

enyl

ethy

lhyd

razi

nesu

lfat

eP

roca

rbaz

ine

HC

lz N

-N-P

ropy

l-N

-for

myl

hydr

azin

eP

ropy

lhyd

razi

neH

Cl

Sel

eniu

msu

lde

z S

trep

tozo

toci

nz Su

lfal

late

z Te

lone

IIt

echn

ical

grad

ez 3

34

4-T

etra

amin

obip

heny

l4H

Clz

Tetr

anitr

omet

hane

z T-

2to

xin

Tri

chlo

roet

hyle

nez

Tri

ura

lint

echn

ical

grad

ey 2

45-

Tri

met

hyla

nilin

eH

Clz

Tri

s(2

3-di

brom

opro

pyl)

phos

phat

ez U

reth

anez

Vin

ylch

lori

dez

Vin

ylu

orid

ez V

inyl

iden

ech

lori

dey

24-

Xyl

idin

eH

Cly

Mon

key

1U

reth

anez

Rat

551-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro

-2-f

uryl

) -1

34-

oxad

iazo

le2

-Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-5-

nitr

othi

azol

ey 1-

Am

yl-1

-nitr

osou

rea

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is-(

chlo

rom

ethy

l)et

herz

HC

blue

no1

z B

rom

oeth

anez

N-n

-But

yl-N

-nit

roso

urea

Cad

miu

mch

lori

deC

adm

ium

sulp

hate

( 11

) 1-

Chl

oroe

thyl

nitr

oso-

3-( 2

-hyd

roxy

prop

yl) u

rea

Chl

orop

rene

z C

obal

tsul

fate

hept

ahyd

rate

z 1

2-D

ibro

moe

than

ez D

imet

hylh

ydro

gen

phos

phit

ey tr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-

[ 2-(

5-ni

tro-

2-fu

ryl)

viny

l] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

12-

Epo

xybu

tane

y 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

Hyd

razi

nez

Hyd

razi

nesu

lfat

ez 1-

( 2-H

ydro

xyet

hyl)

-1-n

itro

sour

eaz

Isob

utyl

nitr

itez

Ison

iazi

dz 4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4-

( Met

hyln

itros

amin

o)-1

-(3-

pyri

dyl)

-1-b

utan

ol4

-(M

ethy

lnit

rosa

min

o)-1

-(3-

pyri

dyl)

-1-(

buta

none

) N

-[ 3

-(5-

Nitr

o-2-

fury

l)-

12

4-ox

adia

zole

-5-y

l] -m

ethy

lace

tam

ide

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

3-N

itro-

3-he

xene

z 5-

Nitr

oace

naph

then

ez N

-Nit

roso

-bis

-(4

44-

tri

uoro

-N-b

utyl

) am

ine

N-N

itros

o-N

-met

hyl-

N-d

odec

ylam

ine

N-N

itros

o-N

-met

hyl-

N-t

etra

decy

lam

ine

N-N

itro

so-N

-met

hyld

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

lure

az N

-Nitr

osob

is( 2

-hyd

roxy

prop

yl)

amin

eN

-Nitr

osob

is-2

3-d

ihyd

roxy

prop

ylam

ine

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itros

odim

ethy

lam

inez

N-N

itro

soep

hedr

ine

Nitr

osoe

thyl

met

hyla

min

eN

-Nit

roso

met

hyl

N-N

itro

som

ethy

l-( 3

-hyd

roxy

prop

yl) a

min

eN

itro

som

ethy

lund

ecyl

amin

eC

Ia

cid

red

114

Sod

ium

dich

rom

ate

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tetr

anit

rom

etha

nez

24

5-T

rim

ethy

lani

line

z 2

46-

Tri

met

hyla

nili

neH

Clz

Vin

ylch

lori

dez

Mam

mar

ygl

and

Dog

1Ly

nest

reno

lH

amst

er1

Vin

ylch

lori

dez

Mou

se24

5-A

zacy

tidin

ez B

enze

nez

CI

dir

ectb

lack

381

3-B

utad

iene

z C

alci

fero

lC

hlor

opre

nez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Die

thyl

stilb

estr

olz

a-E

cdys

one

Est

radi

olE

thyl

ene

oxid

ez F

uros

emid

ey G

lyci

dolz

Gri

seof

ulvi

nIs

onia

zidz

Ison

icot

inic

acid

vani

llylid

eneh

ydra

zide

( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Nitr

oben

zene

z R

eser

pine

z Su

lfal

late

z V

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y

644

Rat

102

4-A

cety

lam

inob

iphe

nyl

2-A

cety

lam

ino

uore

nez

Acr

onyc

ine

Acr

ylam

ide

Acr

ylon

itri

leA

F-2

z 1-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro-

2-fu

ryl)

-13

4-

oxad

iazo

le2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

e2-

Am

ino-

5-ni

trot

hiaz

oley

4-A

min

odip

heny

lHC

l1-

Am

yl-1

-nit

roso

urea

Atr

azin

ey B

emit

radi

ne

Ben

zidi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

4-B

is( 2

-hyd

roxy

ethy

l)am

ino-

2-( 5

-nit

ro-2

-thi

enyl

) qui

nazo

line

13-

But

adie

nez

N-n

-But

yl-N

-nitr

osou

rea

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Car

boxy

met

hyln

itros

oure

aC

hlor

ambu

cilz

Chl

orop

rene

z C

ytem

bena

y D

acar

bazi

nez

N-1

-Dia

ceta

mid

ouo

rene

46

-Dia

min

o-2-

( 5-n

itro-

2-fu

ryl)

-S-t

riaz

ine

24-

Dia

min

oani

sole

sulf

atez

24-

Dia

min

otol

uene

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dib

rom

oman

nito

lz 1

3-D

ibut

yl-1

-nit

roso

urea

33

-Dic

hlor

oben

zidi

ne1

2-D

ichl

oroe

than

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

12-

Dim

ethy

l-5-

nitr

oim

idaz

ole

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lam

inoe

thyl

nitr

osoe

thyl

urea

nitr

ite

salt

33

-Dim

ethy

lben

zidi

ne2

HC

lz 2-

( 22

-Dim

ethy

lhyd

razi

no) -

4-( 5

-nitr

o-2-

fury

l)th

iazo

le

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

24-

Dio

xane

z 1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

6-di

nitr

otol

uene

)zN

-(2-

Fluo

reny

l)-2

22

-tri

uo

roac

etam

ide

Form

icac

id2-

( 4-m

ethy

l-2-

thia

zoly

l)hy

draz

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-

thia

zoly

l] hyd

razi

dez

Gly

cido

lz H

exam

ethy

lmel

amin

eN

-Hex

ylni

tros

oure

a2-

Hyd

razi

no-4

-(p-

amin

ophe

nyl)

thia

zole

z 2-

Hyd

razi

no-4

-( 5

-nit

ro-2

-fur

yl) t

hiaz

olez

2-H

ydra

zino

-4-(

p-ni

trop

heny

l)th

iazo

lez

Hyd

razo

benz

enez

1-( 2

-Hyd

roxy

ethy

l)-3

-[( 5

-nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

e1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

1-(

2-H

ydro

xyet

hyl)

-1-n

itros

oure

az In

dom

etha

cin

IQz

IQH

Cl

Ison

iazi

dz 2-

Met

hoxy

-3-a

min

odib

enzo

fura

n4-

Met

hyl-

1-[(

5-ni

trof

urfu

rylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

-(N

-Met

hyl-

N-n

itro

soca

rbam

oyl)

-l-o

rnit

hine

3-M

ethy

lcho

lant

hren

e4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line)

Met

hyle

nech

lori

dez

Met

roni

dazo

lez

l-5-

Mor

phol

inom

ethy

l-3-

[(5-

nitr

ofur

fury

lide

ne) a

min

o]-

2-ox

azol

idin

one

HC

lN

ithia

zide

z 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

3-( 5

-Nitr

o-2-

fury

l)-i

mid

azo(

12-

a)

pyri

dine

z 4-

( 5-N

itro-

2-fu

ryl)

thia

zole

N

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

ide

NN

-[6-

( 5-N

itro

-2-f

uryl

) -S-

tria

zine

-24

-diy

l] bis

acet

amid

e5-

Nitr

oace

naph

then

ez 1-

[(5-

Nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

itrom

etha

nez

1-N

itrop

yren

eN

orle

stri

nz O

chra

toxi

nA

z N

-(9-

Oxo

-2-

uore

nyl)

acet

amid

ePh

enac

etin

z Ph

enes

teri

nz Ph

IPH

Clz

Proc

arba

zine

HC

lz Pr

opan

esu

lton

e1

2-Pr

opyl

ene

oxid

ez St

yren

ey Su

lfal

late

z 4

4-S

ulfo

nylb

isac

etan

ilid

eTo

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uor

o-N

-[4-

( 5-n

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

idez

Trp

-P-2

acet

atez

Vin

ylch

lori

dez

FD

ampC

viol

etno

1y

Mes

ovar

ium

Rat

2Sa

lbut

amol

Ter

buta

line

Myo

card

ium

Mou

se2

Est

radi

olm

usta

rdy

Phen

este

rinz

Nas

alca

vity

bB

ush

baby

1N

-Nitr

osod

ieth

ylam

ine

Ham

ster

11A

ceta

ldeh

yde

Dia

llyln

itros

amin

eD

imet

hylc

arba

myl

chlo

ride

Hyd

razi

nez

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osom

ethy

l-2

3-di

hydr

oxyp

ropy

lam

ine

N-N

itros

omor

phol

ine

N-N

itros

onor

nico

tine

N-N

itros

opip

erid

inez

Mou

se6

Ally

lgly

cidy

leth

ery

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 1

2-D

ibro

moe

than

ez Fo

rmal

dehy

dez

N-N

itro

sohe

xam

ethy

lene

imin

e1

2-Pr

opyl

ene

oxid

ez

Rat

43A

ceta

ldeh

yde

Acr

ylon

itril

e1-

Azo

xypr

opan

eB

enze

nez

Bis

-(ch

loro

met

hyl)

ethe

rz p-

Cre

sidi

nez

Dia

llyln

itros

amin

e1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dim

ethy

lnitr

amin

eD

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

e1

4-D

ioxa

nez

12-

Epo

xybu

tane

y Z

-Eth

yl-O

NN

-azo

xyet

hane

E

thyl

benz

ene

Eth

ylni

tros

ocya

nam

ide

Form

alde

hyde

z H

exam

ethy

lpho

spho

ram

ide

Hyd

razi

nez

N-N

itro

so-N

-met

hyld

ecyl

amin

edi

( N-N

itro

so) -

perh

ydro

pyri

mid

ine

N-N

itros

o(2

22-

tri

uoro

ethy

l)et

hyla

min

e1-

Nitr

oso-

34

5-tr

imet

hylp

iper

azin

eN

-Nitr

osoa

llyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyle

than

olam

ine

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

dipr

opyl

amin

eN

itros

oeth

ylm

ethy

lam

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nitr

osom

ethy

l-( 2

-hyd

roxy

ethy

l)am

ine

N-N

itro

som

ethy

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

norn

icot

ine-

1-N

-oxi

de

N-N

itro

sopi

peri

dine

z P

hena

cetin

z Ph

enyl

glyc

idyl

ethe

r1

2-Pr

opyl

ene

oxid

ez V

inyl

acet

atez

Vin

ylch

lori

dez

Ner

vous

Mou

se3

13-

But

adie

nez

N-N

itros

odim

ethy

lam

inez

Pro

carb

azin

eH

Clz

syst

emR

at21

Acr

ylam

ide

Acr

ylon

itril

eB

rom

oeth

anez

Chl

oram

buci

lz 1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

eC

yclo

phos

pham

idez

1-E

thyl

-1-n

itros

oure

aE

thyl

eneo

xide

z 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

eaG

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

R(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

S(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

M

ethy

lnit

ram

ine

N-N

itros

o-N

-met

hylu

reaz

N-N

itros

odie

than

olam

ine

1-P

heny

l-3

3-di

met

hyltr

iaze

neP

roca

rbaz

ine

HC

lz P

ropa

nesu

ltone

Vin

ylch

lori

dez

Ora

lcav

ityc

Ham

ster

4A

ceta

ldeh

yde

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itros

omor

phol

ine

N-N

itro

sopi

peri

dine

z

Mou

se3

N-N

itros

ohex

amet

hyle

neim

ine

12

3-T

rich

loro

prop

anez

Vin

ylac

etat

ez

Rat

32A

cryl

amid

eA

cryl

onitr

ile

Ben

zene

z 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

CI

dir

ectb

lue

15C

Id

irec

tblu

e21

8z C

hlor

opre

nez

3-D

iazo

tyra

min

eH

Cl

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

eG

lyci

dolz

IQz

MeA

-a-C

acet

atez

N-N

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

hydr

oxyp

ropy

lam

ine

Nit

roso

-23

-dih

ydro

xypr

opyl

-2-

oxop

ropy

lam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

itro

soam

ylur

etha

nN

-Nitr

osod

ieth

ylam

ine

Nit

roso

ethy

lure

than

N

itros

ohep

tam

ethy

lene

imin

e1-

Nitr

osoh

ydan

toin

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

thia

ldin

eN

-Nitr

osot

hiom

orph

olin

eC

Ia

cid

red

114

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tolu

eney

12

3-T

rich

loro

prop

anez

Xyl

ene

mix

ture

( m-x

ylen

eo-

xyle

nep

-xyl

ene)

Ova

ryM

ouse

10B

enze

nez

13-

But

adie

nez

Die

thyl

stil

best

rolz

N-M

ethy

lola

cryl

amid

ey 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

5-N

itroa

cena

phth

enez

1-[(

5-N

itro

furf

uryl

iden

e)am

ino]

hyda

ntoi

nz P

heno

lpht

hale

inz

Tam

oxif

enci

trat

ez 4-

Vin

ylcy

cloh

exen

ePa

ncre

asH

amst

er3

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

itro

so-2

6-d

imet

hylm

orph

olin

eN

itro

so-2

-oxo

prop

ylet

hano

lam

ine

Mon

key

1U

reth

anez

Rat

222-

Am

ino-

5-ni

trop

heno

ly 1-

( Am

inom

ethy

l)cy

cloh

exan

eace

ticac

idA

zase

rine

But

ylbe

nzyl

phth

alat

ey C

hlor

endi

cac

idz

Cin

nam

ylan

thra

nila

tez

Clo

bra

tey

Dic

hlor

vosz

Eth

ylal

coho

ly H

ydro

chlo

ro

uoro

carb

on12

3IQ

HC

lM

alon

alde

hyde

sod

ium

saltz

MeA

-a-C

acet

atez

2-M

erca

ptob

enzo

thia

zole

y M

ethy

lclo

fena

pate

z N

-(N

-Met

hyl-

N-n

itros

ocar

bam

oyl)

-l-o

rnit

hine

4-(

Met

hyln

itro

sam

ino)

-1-(

3-py

ridy

l)-1

-but

anol

4-(

Met

hyln

itros

amin

o)-1

-( 3

-pyr

idyl

) -1-

( but

anon

e)N

afen

opin

Nitr

ofen

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)z1

23

-Tri

chlo

ropr

opan

ez

Peri

tone

alM

ouse

8B

is-1

2-(

chlo

rom

etho

xy) e

than

eB

is-1

4-(

chlo

rom

etho

xy) -

p-xy

lene

Bis

-(ch

loro

met

hyl)

ethe

rz C

hlor

opre

nez

tran

s-1

4-D

ichl

orob

uten

e-2

cavi

tyD

imet

hylc

arba

myl

chlo

ride

Phe

noxy

benz

amin

eH

Clz

Tri

s-1

23-

( chl

orom

etho

xy) p

ropa

neR

at22

Acr

onyc

ine

Acr

ylam

ide

Act

inom

ycin

DA

nili

neH

Cly

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

rom

ate

pota

ssiu

mz

Chl

oroz

otoc

in

Cyt

embe

nay

Dap

sone

y 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

4-D

ioxa

nez

Eth

ylen

eox

idez

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz M

elph

alan

z N

-Met

hyl-

N4

-din

itros

oani

line

Mit

omyc

in-C

N-N

itro

so-2

24

-tri

met

hyl-

12-

dihy

droq

uino

line

poly

mer

Ph

enox

yben

zam

ine

HC

lz o-

Tolu

idin

eH

Clz

( Con

tinue

don

next

page

)

645

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Pitu

itar

ygl

and

Mou

se8

Die

thyl

stil

best

rolz

Eno

vid

Eth

ylen

eth

iour

eaz

Iodi

nate

dgl

ycer

olz

Isop

rene

Nor

lest

rinz

Pro

pylt

hiou

raci

lz Z

eara

leno

ney

Rat

73-

Am

inot

riaz

olez

12-

Dib

rom

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylal

coho

ly 2-

Mer

capt

oben

zoth

iazo

ley

Met

roni

dazo

lez

Nor

lest

rinz

Pros

tate

Rat

4C

adm

ium

chlo

ride

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

PhIP

HC

lz

Skin

Ham

ster

2U

reth

anez

Vin

ylch

lori

dez

Mou

se5

5-A

zacy

tidin

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Chl

orop

rene

z G

lyci

dolz

Thi

o-te

paz

Rat

332-

Ace

tyla

min

ouo

rene

z 3-

Am

ino-

9-et

hylc

arba

zole

mix

ture

z 1-

Azo

xypr

opan

e2-

Azo

xypr

opan

eB

enze

nez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

ol

tech

nica

lgra

dez

CI

dir

ectb

lue

15C

arbo

xym

ethy

lnitr

osou

rea

24-

Dia

min

oani

sole

sulf

atez

Dib

rom

odul

cito

lz D

ibro

mom

anni

tolz

Dim

etho

xane

2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

Dim

ethy

lvin

ylch

lori

dez

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

26-

dini

trot

olue

ne)z

1-E

thyl

nitr

oso-

3-( 2

-hyd

roxy

ethy

l)-u

rea

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz 1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

IQ

z L

asio

carp

ine

MeI

Qxz

N-(

N-M

ethy

l-N

-nitr

osoc

arba

moy

l)-l

-orn

ithi

ne

5-N

itro-

o-an

isid

inez

CI

aci

dre

d11

4p-

Ros

anili

neH

Clz

Thi

o-te

paz

Thi

oure

ay V

inyl

chlo

ride

z F

Damp

Cvi

olet

no1

y

Smal

lint

esti

neM

ouse

6C

apta

folz

Cap

tanz

N-E

thyl

-N-n

itro

-N-n

itro

sogu

anid

ine

Hyd

roge

npe

roxi

deN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-(

Tri

chlo

rom

ethy

lthi

o)ph

thal

imid

eM

onke

y1

Ure

than

ez

Rat

29A

cryl

onitr

ile

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is( 2

3-d

ibro

mop

ropy

l)ph

osph

ate

mag

nesi

umsa

lt4

-Bis

( 2-h

ydro

xyet

hyl)

amin

o-2-

( 5-n

itro

-2-t

hien

yl) q

uina

zolin

eC

Id

irec

tblu

e15

Car

boxy

met

hyln

itros

oure

a1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

e2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro

-2-f

uryl

)py

rim

idin

etr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-[

2-( 5

-nit

ro-2

-fur

yl) v

inyl

] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

Z-E

thyl

-ON

N-a

zoxy

met

hane

1-E

thyl

-1-n

itros

oure

aFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lu-P

-1z

Glu

-P-2

z IQ

z L

asio

carp

ine

N-M

ethy

l-N

-nitr

o-N

-nitr

osog

uani

dine

z N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez N

-Nitr

oso-

N-i

sobu

tylu

rea

3-N

itro

so-2

-oxa

zoli

dino

neN

itro

soet

hylu

reth

ane

PhI

PH

Clz

Pro

pane

sulto

neQ

uerc

etin

y C

Ia

cid

red

114

Trp

-P-2

acet

atez

Sple

enR

at7

Ani

line

HC

ly A

zobe

nzen

ey p-

Chl

oroa

nili

neH

Clz

Dap

sone

y o-

Nitr

osot

olue

neD

ampC

red

no9

y o-

Tolu

idin

eH

Clz

Stom

ach

Ham

ster

18A

F-2z

14-

Din

itros

o-2

6-di

met

hylp

iper

azin

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z H

ydra

zine

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] a

ceta

mid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

N-N

itro

so-2

3-d

ihyd

roxy

prop

yl-2

-hyd

roxy

prop

ylam

ine

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

-Nitr

oso-

ethy

l-2-

oxop

ropy

lure

aN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

itros

o-5-

met

hylo

xazo

lidon

eN

-Nit

roso

-N-m

ethy

lure

than

N-N

itros

o-1

3-ox

azol

idin

eN

-Nit

roso

-2-p

heny

leth

ylur

ea1

-Nit

roso

-34

5-t

rim

ethy

lpip

eraz

ine

Ure

than

ez V

inyl

chlo

ride

z

Mou

se63

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eA

ciu

orfe

nA

F-2

z 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

tran

s-5-

Am

ino-

3[2-

( 5-n

itro-

2-fu

ryl)

viny

l] -1

24-

oxad

iazo

leA

reco

line

HC

lB

enza

ldeh

ydey

Ben

zofu

ranz

Ben

zotr

ichl

orid

eB

enzy

lace

tate

y B

enzy

lchl

orid

ey B

rom

oeth

anol

13

-But

adie

nez

But

ylat

edhy

drox

yani

sole

z 1

1-di

-N-B

utyl

hydr

azin

eC

affe

icac

idz

Cap

tafo

lz C

arba

zole

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z3

-(C

hlor

omet

hyl)

pyri

dine

HC

lz C

hlor

opre

nez

2-C

hlor

opro

pana

l1-

Chl

orop

rope

neC

ypro

tero

neac

etat

e1

1-D

ially

lhyd

razi

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dic

hlor

vosz

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez D

imet

hylv

inyl

chlo

ride

z D

init

roso

pipe

razi

neE

stra

diol

mus

tard

y E

thyl

acry

late

z Fo

rmic

acid

2-[ 4

-( 5

-nit

ro-2

-fur

yl) -

2-th

iazo

lyl] h

ydra

zide

z G

lyci

dolz

2-H

ydra

zino

-4-(

5-ni

tro-

2-fu

ryl)

thia

zole

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

ICI

1628

46z

IQz

Isop

rene

Lov

asta

tin

MeI

Q1

-Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m3

-(5-

Nitr

o-2-

fury

l)-

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] f

orm

amid

ez N

-Nit

roso

-N

-met

hylu

reaz

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

hexa

met

hyle

neim

ine

N-N

itros

opip

erid

inez

b-P

ropi

olac

tone

z Se

sam

olz

Sty

rene

oxid

ez Te

lone

IIt

echn

ical

grad

ez N

-(T

rich

loro

met

hylth

io) p

htha

limid

e1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uo

ro-N

-[4-

( 5-n

itro

-2-f

uryl

) -2-

thia

zoly

l]ac

etam

idez

Tri

ur

alin

tec

hnic

algr

adey

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylac

etat

ez

Rat

85A

ceto

ne[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zone

1-A

ceto

xysa

frol

ey A

cryl

onitr

ile

1-A

llyl

-1-n

itro

sour

ea2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-ox

adia

zole

2-

Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-4-

( 5-n

itro

-2-f

uryl

) thi

azol

ez 1-

Am

yl-1

-nit

roso

urea

Ari

stol

ochi

cac

id

sodi

umsa

lt( 7

7A

AI

21

AA

II)

Ben

zene

z B

enzo

( a) p

yren

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

BL

-634

1H

Cl

N-n

-But

yl-N

-nitr

osou

rea

But

ylat

edhy

drox

yani

sole

z b

-But

yrol

acto

neC

affe

icac

idz

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z4

-Chl

oro-

o-ph

enyl

ened

iam

inez

Chl

oro

uoro

met

hane

3-

( Chl

orom

ethy

l)py

ridi

neH

Clz

Cip

rob

rate

z C

upfe

rron

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez 2

5-D

imet

hoxy

-4-a

min

osti

lben

ez D

imet

hylh

ydro

gen

phos

phit

ey 4

6-D

imet

hyl-

2-( 5

-nit

ro-2

-fu

ryl)

pyri

mid

ine

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lvin

ylch

lori

dez

Epi

chlo

rohy

drin

y E

thyl

acry

late

z E

thyl

ene

oxid

ez 2-

Flu

oroe

thyl

-nitr

osou

rea

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-

nitr

osou

reaz

1-( 3

-Hyd

roxy

prop

yl) -

1-ni

tros

oure

a1

-Hyd

roxy

safr

olez

ICI

1628

46z

Lox

tidin

eL

upit

idin

e3H

Cl

Mer

curi

cch

lori

dey

3-M

etho

xyca

tech

ol4

-Met

hoxy

phen

olN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-M

ethy

l-N

-nit

roso

benz

amid

e4-

Met

hylc

atec

hol

Met

hyln

itro

socy

anam

ide

3-( 5

-Nit

ro-2

-fur

yl) -

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

4-( 5

-Nit

ro-2

-fur

yl) t

hiaz

ole

2-N

itro

uo

rene

8-N

itro

quin

olin

eN

itro

so-B

aygo

nN

-Nit

roso

-23

-dih

ydro

xypr

opyl

-2-h

ydro

xypr

opyl

amin

eN

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

oxop

ropy

lam

ine

1-N

itro

so-3

5-d

imet

hyl-

4-be

nzoy

lpip

eraz

ine

N-N

itro

so-N

-met

hyl-

N-d

odec

ylam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itro

so-N

-met

hylu

reaz

Nit

roso

-12

36

-tet

rahy

drop

yrid

ine

N-N

itro

sobe

nzth

iazu

ron

Nitr

osod

ibut

ylam

inez

N-N

itros

odie

thyl

amin

eN

-Nit

roso

ephe

drin

eN

itros

oeth

ylur

etha

nO

mep

razo

ley

Phen

acet

inz

Piv

alol

acto

ney

b-P

ropi

olac

tone

z N

-Pro

pyl-

N-n

itro

-N-n

itro

sogu

anid

ine

12-

Pro

pyle

neox

idez

Ses

amol

z St

yren

eox

idez

Sulf

alla

tez

Telo

neII

tec

hnic

algr

adez

12

3-T

rich

loro

prop

anez

24

6-T

rim

ethy

lani

line

HC

lz

646

Subc

utan

eous

Mou

se4

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

2-D

ibro

moe

than

ez N

2-c

-Glu

tam

yl-p

-hyd

razi

nobe

nzoi

cac

idG

lyci

dolz

tissu

eR

at13

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ichl

oroe

than

ez D

imet

hoxa

ne1

4-D

ioxa

nez

MeA

-a-C

acet

atez

44

-Met

hyle

ne-b

is( 2

-met

hyla

nili

ne)

o-N

itro

soto

luen

ep-

Ros

anili

neH

Clz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 2

45-

Tri

met

hyla

nilin

eH

Clz

25-

Xyl

idin

eH

Clz

Test

isM

ouse

4D

ieth

ylst

ilbe

stro

lz Fi

nast

erid

eR

eser

pine

z Ta

mox

ifen

citr

atez

Rat

185-

Aza

cytid

inez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

3-B

utad

iene

z N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

Cad

miu

mch

lori

de

2-C

hlor

o-1

11-

tri

uoro

etha

ne1

1-D

ichl

oro-

1-u

oroe

than

eH

ydro

chlo

rou

oroc

arbo

n12

3M

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z M

etro

nida

zole

z N

-Nit

roso

dim

ethy

lam

inez

Oxo

linic

acid

y SD

Z20

0-11

01

11

2-Te

tra

uoro

etha

ney

Tri

chlo

roet

hyle

nez

Tri

nitr

ogly

ceri

nV

inyl

chlo

ride

z

Thy

roid

glan

dH

amst

er4

Hex

achl

orob

enze

nez

Hyd

razi

nez

Met

hylt

hiou

raci

lU

reth

anez

Mou

se18

3-A

min

o-4-

etho

xyac

etan

ilide

y H

Cbl

ueno

1z

tert

-But

ylal

coho

lz C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

24

-Dia

min

oani

sole

sulf

atez

Die

thyl

stil

best

rolz

Dox

ylam

ine

succ

inat

ez E

thio

nam

idey

Eth

ylen

eth

iour

eaz

44

-Met

hyle

nedi

anil

ine

2HC

lz 1

5-N

apht

hale

nedi

amin

ez N

itrob

enze

nez

Oxa

zepa

my

44

-Oxy

dian

iline

z C

Ip

igm

entr

ed3z

Sulf

amet

hazi

ne2

37

8-T

etra

chlo

rodi

benz

o-p-

diox

inz

44

-Thi

odia

nilin

ez

Rat

33A

cryl

amid

e3-

Am

inot

riaz

olez

o-A

nisi

dine

HC

lz B

emit

radi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

Chl

orop

rene

z 2

4-D

iam

inoa

niso

lesu

lfat

ez N

N-D

ieth

ylth

iour

eay

1-E

thyl

-1-n

itro

sour

ea

Eth

ylen

eth

iour

eaz

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Flu

vast

atin

Gly

cido

lz Io

dina

ted

glyc

erol

z Is

obut

eney

Mal

onal

dehy

des

odiu

msa

ltz

Met

him

azol

e4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Mir

exp

hoto

-N

itro

benz

enez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

44

-Oxy

dian

iline

z Pr

opyl

thio

urac

ilz p-

Ros

anil

ine

HC

lz 2

37

8-Te

trac

hlor

odib

enzo

-p-d

ioxi

nz 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tri

met

hylt

hiou

reay

Vin

ylac

etat

ez Z

inc

dim

ethy

ldith

ioca

rbam

atez

Uri

nary

blad

der

Dog

23

3-D

ichl

orob

enzi

dine

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nilin

e)H

amst

er3

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

acet

amid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

Mou

se12

2-A

cety

lam

ino

uore

nez

4-A

min

odip

heny

l2-

Am

inod

iphe

nyle

neox

ide

o-A

nisi

dine

HC

lz 4-

Chl

oro-

4-a

min

odip

heny

leth

erz

p-C

resi

dine

z 4-

Eth

ylsu

lpho

nyln

apht

hale

ne-1

-sul

fona

mid

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hena

cetin

z Te

lone

IIt

echn

ical

grad

ez U

raci

lz

Mon

key

12-

Nap

hthy

lam

inez

Rat

49A

ceta

min

ophe

nz A

llyli

soth

iocy

anat

ey 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

4-A

min

o-2-

nitr

ophe

noly

11-A

min

ound

ecan

oic

acid

y o-

Ani

sidi

neH

Clz

Ari

stol

ochi

cac

ids

odiu

msa

lt( 7

7A

AI

21

AA

II)

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

ispe

rse

blue

1y N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

4-C

hlor

o-o-

phen

ylen

edia

min

ez m

-Cre

sidi

ney

p-C

resi

dine

z C

yclo

phos

pham

idez

Die

thyl

ene

glyc

olD

imet

hyla

rsin

icac

idy

Fose

tylA

lIQ

HC

lM

eA-a

-Cac

etat

ez M

elam

iney

2-M

etho

xy-3

-am

inod

iben

zofu

ran

2-N

apht

hyla

min

ez N

itril

otri

acet

icac

idz

Nitr

ilot

riac

etic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez o-

Nitr

oani

sole

z N

-Nitr

oso-

N-m

ethy

l-N

-dod

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

l-N

-tet

rade

cyla

min

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itro

sodi

phen

ylam

iney

o-N

itros

otol

uene

N-O

xydi

ethy

lene

thio

carb

amyl

-N-o

xydi

ethy

lene

sulf

enam

ide

Phe

nace

tinz

Phen

azon

eo-

Phen

ylph

enat

eso

dium

y o-

Phen

ylph

enol

y P

otas

sium

bica

rbon

ate

Purp

urin

Que

rcet

iny

p-Q

uino

nedi

oxim

ey Sa

ccha

rin

sodi

umy

Sali

cyla

zosu

lfap

yrid

inez

o-To

luen

esul

fona

mid

eo-

Tolu

idin

eH

Clz

Trp

-P-2

acet

atez

Ura

cilz

Ute

rus

Ham

ster

1N

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aM

ouse

12B

rom

oeth

anez

Chl

oroe

than

ey D

acar

bazi

nez

12-

Dic

hlor

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylen

eox

idez

Gly

cido

lz ( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Proc

arba

zine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez T

rim

ethy

lpho

spha

tey

Vin

ylac

etat

ez

Rat

26A

cryl

amid

e1-

Ally

l-1-

nitr

osou

rea

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

myl

-1-n

itros

oure

aA

traz

iney

CI

dir

ectb

lue

15B

rom

ocri

ptin

em

esyl

atey

N-n

-But

yl-N

-nit

roso

urea

Cal

cium

valp

roat

eC

apta

nz 2-

Chl

oro-

11

1-tr

iuo

roet

hane

Dac

arba

zine

z D

amin

ozid

ez 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

lD

imet

hyla

min

oeth

ylni

tros

oeth

ylur

ean

itri

tesa

lt1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

ICR

F-1

59z

Isop

hosp

ham

idez

15-

Nap

htha

lene

diam

inez

Nit

robe

nzen

ez N

orle

stri

nz 4

4-T

hiod

iani

linez

Vin

ylac

etat

ez

Vag

ina

Mou

se1

AZ

Tz

Rat

2A

ZT

z N

-n-B

utyl

-N-n

itro

sour

ea( C

ontin

ued

onne

xtpa

ge)

647

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Vas

cula

rsy

stem

Ham

ster

91

2-D

imet

hylh

ydra

zine

2H

Cl

Gly

cido

lz H

exac

hlor

oben

zene

z N

-Nit

roso

-eth

yl-2

-oxo

prop

ylur

eaN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

-Nitr

oso-

oxop

ropy

lchl

oroe

thyl

urea

N-N

itro

so-o

xopr

opyl

urea

N-N

itros

o-2-

phen

ylet

hylu

rea

Vin

ylch

lori

dez

Mou

se59

A-a

-CN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-ph

enyl

hydr

azin

eA

llyl

hydr

azin

eH

Cl

Are

colin

eH

Cl

Aza

thio

prin

eB

enzi

dine

2H

Cl

2-B

iphe

nyla

min

eH

Cly

13-

But

adie

nez

Cap

tafo

lz C

arba

myl

hydr

azin

eH

Cl

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 1-

Chl

oro-

4-ni

trob

enze

ney

5-C

hlor

o-o-

tolu

idin

ey 4-

Chl

oro-

o-to

luid

ine

HC

ly p-

Chl

oroa

nilin

eH

Clz

Chl

orop

rene

z C

upfe

rron

z D

acar

bazi

nez

Dam

inoz

idez

24-

Dia

min

otol

uene

2H

Clz

12-

Dib

rom

oeth

anez

Dif

talo

ne7

12-

Dim

ethy

lben

z(a)

anth

race

ne1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylhy

draz

ine

HC

lG

lu-P

-1z

Glu

-P-2

z p-

Hyd

razi

nobe

nzoi

cac

idH

Cl

1-H

ydro

xysa

frol

ez Is

opre

neM

eA-a

-Cac

etat

ez N

-Met

hyl-

N-f

orm

ylhy

draz

ine

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

Mic

hler

rsquoske

tone

z 5-

Nitr

o-o-

tolu

idin

ey N

itro

fenz

N-N

itros

o-N

-met

hylu

reaz

Pent

achl

oroa

niso

lez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y2

34

56

-Pen

tach

loro

phen

olt

echn

ical

grad

ez n-

Pen

tylh

ydra

zine

HC

lPh

enyl

ethy

lhyd

razi

nesu

lfat

ePh

enyl

hydr

azin

eH

Cl

Ster

igm

atoc

ysti

nz Te

tra

uoro

ethy

lene

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)zo

-Tol

uidi

neH

Clz

24

6-T

rich

loro

anil

iney

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nili

neH

Clz

Ure

than

ez V

inyl

carb

amat

eV

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y 2

5-X

ylid

ine

HC

lz

Mon

key

2A

ato

xin

B1y

Ure

than

ez

Rat

32A

nilin

eH

Cly

Azo

benz

eney

Ben

zene

z C

livor

ine

Cup

ferr

onz

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neI

QH

Cl

Las

ioca

rpin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line)

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-N

itros

o-( 2

-hyd

roxy

prop

yl) -

( 2-h

ydro

xyet

hyl)

amin

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nitr

osob

is( 2

-oxo

prop

yl) a

min

eN

-Nit

roso

diet

hano

lam

ine

N-N

itro

sodi

ethy

lam

ine

N-N

itros

odim

ethy

lam

inez

N-N

itros

omet

hyl-

( 2-t

osyl

oxye

thyl

) am

ine

N-N

itros

omor

phol

ine

N-N

itro

sopy

rrol

idin

ez Pe

tasi

teni

neS

teri

gmat

ocys

tinz

Sym

phyt

ine

Tetr

auo

roet

hyle

nez

o-To

luid

ine

HC

lz T

rp-P

-2ac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

aT

here

was

nore

port

edta

rget

site

in1

spec

ies

( rat

sor

mic

e)fo

r5

chem

ical

sw

ithsu

pers

crip

tsb

utth

ech

emic

alw

asev

alua

ted

byth

epu

blis

hed

auth

oras

aca

rcin

ogen

ald

rinz

diel

drin

z N

-nit

roso

pyrr

olid

inez

23

45

6-pe

ntac

hlor

ophe

nol

( Dow

icid

eE

C-7

)ya

ndur

etha

nez

bN

asal

cavi

tyin

clud

estis

sues

ofth

eno

sen

asal

turb

inat

esp

aran

asal

sinu

ses

and

trac

hea

c Ora

lcav

ityin

clud

estis

sues

ofth

em

outh

oro

phar

ynx

phar

ynx

and

lary

nx

Ach

emic

alis

liste

dun

der

each

orga

nev

alua

ted

aspo

sitiv

ein

anex

peri

men

tin

that

spec

ies

byat

leas

t1au

thor

The

refo

rea

chem

ical

may

beli

sted

unde

rse

vera

ltar

geto

rgan

san

dev

ery

chem

ical

liste

din

the

tabl

eis

posi

tive

inat

leas

t1sp

ecie

sIn

orde

rto

com

pare

resu

ltsin

rats

and

mic

esy

mbo

lsfo

llow

chem

ical

ste

sted

inbo

thsp

ecie

sa

zin

dica

tes

that

the

chem

ical

ispo

sitiv

eat

som

esi

tein

both

spec

ies

and

ay

indi

cate

sth

atit

was

test

edin

both

butp

ositi

vein

only

1a

Nth

enu

mbe

rof

chem

ical

sw

ithat

leas

t1po

sitiv

ete

stat

that

site

inth

atsp

ecie

sB

ecau

sem

any

chem

ical

sin

duce

tum

ors

atm

ore

than

1si

tein

agi

ven

spec

ies

man

ych

emic

als

appe

arm

ore

than

once

inth

eta

ble

648

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649

species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters

RESULTS IN RATS AND MICE

For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens

TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database

Chemicals evaluated as carcinogenic in

Rats Mice

All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)

Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2

a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not

b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats

All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical

to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included

The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site

Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 7: Compendium of Chemical Carcinogens by Target Organ - Toxnet

Rat

102

4-A

cety

lam

inob

iphe

nyl

2-A

cety

lam

ino

uore

nez

Acr

onyc

ine

Acr

ylam

ide

Acr

ylon

itri

leA

F-2

z 1-

Ally

l-1-

nitr

osou

rea

2-A

min

o-5-

( 5-n

itro-

2-fu

ryl)

-13

4-

oxad

iazo

le2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

e2-

Am

ino-

5-ni

trot

hiaz

oley

4-A

min

odip

heny

lHC

l1-

Am

yl-1

-nit

roso

urea

Atr

azin

ey B

emit

radi

ne

Ben

zidi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

4-B

is( 2

-hyd

roxy

ethy

l)am

ino-

2-( 5

-nit

ro-2

-thi

enyl

) qui

nazo

line

13-

But

adie

nez

N-n

-But

yl-N

-nitr

osou

rea

Cap

tafo

lz C

arbo

nte

trac

hlor

idez

Car

boxy

met

hyln

itros

oure

aC

hlor

ambu

cilz

Chl

orop

rene

z C

ytem

bena

y D

acar

bazi

nez

N-1

-Dia

ceta

mid

ouo

rene

46

-Dia

min

o-2-

( 5-n

itro-

2-fu

ryl)

-S-t

riaz

ine

24-

Dia

min

oani

sole

sulf

atez

24-

Dia

min

otol

uene

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dib

rom

oman

nito

lz 1

3-D

ibut

yl-1

-nit

roso

urea

33

-Dic

hlor

oben

zidi

ne1

2-D

ichl

oroe

than

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

12-

Dim

ethy

l-5-

nitr

oim

idaz

ole

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lam

inoe

thyl

nitr

osoe

thyl

urea

nitr

ite

salt

33

-Dim

ethy

lben

zidi

ne2

HC

lz 2-

( 22

-Dim

ethy

lhyd

razi

no) -

4-( 5

-nitr

o-2-

fury

l)th

iazo

le

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

24-

Dio

xane

z 1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

6-di

nitr

otol

uene

)zN

-(2-

Fluo

reny

l)-2

22

-tri

uo

roac

etam

ide

Form

icac

id2-

( 4-m

ethy

l-2-

thia

zoly

l)hy

draz

ide

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-

thia

zoly

l] hyd

razi

dez

Gly

cido

lz H

exam

ethy

lmel

amin

eN

-Hex

ylni

tros

oure

a2-

Hyd

razi

no-4

-(p-

amin

ophe

nyl)

thia

zole

z 2-

Hyd

razi

no-4

-( 5

-nit

ro-2

-fur

yl) t

hiaz

olez

2-H

ydra

zino

-4-(

p-ni

trop

heny

l)th

iazo

lez

Hyd

razo

benz

enez

1-( 2

-Hyd

roxy

ethy

l)-3

-[( 5

-nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

e1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

1-(

2-H

ydro

xyet

hyl)

-1-n

itros

oure

az In

dom

etha

cin

IQz

IQH

Cl

Ison

iazi

dz 2-

Met

hoxy

-3-a

min

odib

enzo

fura

n4-

Met

hyl-

1-[(

5-ni

trof

urfu

rylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

-(N

-Met

hyl-

N-n

itro

soca

rbam

oyl)

-l-o

rnit

hine

3-M

ethy

lcho

lant

hren

e4

4-M

ethy

lene

-bi

s(2-

chlo

roan

iline

) 4

4-M

ethy

lene

-bis

( 2-m

ethy

lani

line)

Met

hyle

nech

lori

dez

Met

roni

dazo

lez

l-5-

Mor

phol

inom

ethy

l-3-

[(5-

nitr

ofur

fury

lide

ne) a

min

o]-

2-ox

azol

idin

one

HC

lN

ithia

zide

z 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

3-( 5

-Nitr

o-2-

fury

l)-i

mid

azo(

12-

a)

pyri

dine

z 4-

( 5-N

itro-

2-fu

ryl)

thia

zole

N

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

ide

NN

-[6-

( 5-N

itro

-2-f

uryl

) -S-

tria

zine

-24

-diy

l] bis

acet

amid

e5-

Nitr

oace

naph

then

ez 1-

[(5-

Nit

rofu

rfur

ylid

ene)

amin

o]-2

-im

idaz

olid

inon

eN

itrom

etha

nez

1-N

itrop

yren

eN

orle

stri

nz O

chra

toxi

nA

z N

-(9-

Oxo

-2-

uore

nyl)

acet

amid

ePh

enac

etin

z Ph

enes

teri

nz Ph

IPH

Clz

Proc

arba

zine

HC

lz Pr

opan

esu

lton

e1

2-Pr

opyl

ene

oxid

ez St

yren

ey Su

lfal

late

z 4

4-S

ulfo

nylb

isac

etan

ilid

eTo

luen

edi

isoc

yana

te

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uor

o-N

-[4-

( 5-n

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] ace

tam

idez

Trp

-P-2

acet

atez

Vin

ylch

lori

dez

FD

ampC

viol

etno

1y

Mes

ovar

ium

Rat

2Sa

lbut

amol

Ter

buta

line

Myo

card

ium

Mou

se2

Est

radi

olm

usta

rdy

Phen

este

rinz

Nas

alca

vity

bB

ush

baby

1N

-Nitr

osod

ieth

ylam

ine

Ham

ster

11A

ceta

ldeh

yde

Dia

llyln

itros

amin

eD

imet

hylc

arba

myl

chlo

ride

Hyd

razi

nez

Met

hyln

itro

sam

ino-

NN

-dim

ethy

leth

ylam

ine

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itro

soal

lyl-

2-ox

opro

pyla

min

eN

-Nitr

osom

ethy

l-2

3-di

hydr

oxyp

ropy

lam

ine

N-N

itros

omor

phol

ine

N-N

itros

onor

nico

tine

N-N

itros

opip

erid

inez

Mou

se6

Ally

lgly

cidy

leth

ery

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 1

2-D

ibro

moe

than

ez Fo

rmal

dehy

dez

N-N

itro

sohe

xam

ethy

lene

imin

e1

2-Pr

opyl

ene

oxid

ez

Rat

43A

ceta

ldeh

yde

Acr

ylon

itril

e1-

Azo

xypr

opan

eB

enze

nez

Bis

-(ch

loro

met

hyl)

ethe

rz p-

Cre

sidi

nez

Dia

llyln

itros

amin

e1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dim

ethy

lnitr

amin

eD

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

e1

4-D

ioxa

nez

12-

Epo

xybu

tane

y Z

-Eth

yl-O

NN

-azo

xyet

hane

E

thyl

benz

ene

Eth

ylni

tros

ocya

nam

ide

Form

alde

hyde

z H

exam

ethy

lpho

spho

ram

ide

Hyd

razi

nez

N-N

itro

so-N

-met

hyld

ecyl

amin

edi

( N-N

itro

so) -

perh

ydro

pyri

mid

ine

N-N

itros

o(2

22-

tri

uoro

ethy

l)et

hyla

min

e1-

Nitr

oso-

34

5-tr

imet

hylp

iper

azin

eN

-Nitr

osoa

llyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nit

roso

ally

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itro

soal

lyle

than

olam

ine

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

N-N

itro

sodi

etha

nola

min

eN

-Nit

roso

dipr

opyl

amin

eN

itros

oeth

ylm

ethy

lam

ine

N-N

itros

omet

hyl-

23-

dihy

drox

ypro

pyla

min

eN

-Nitr

osom

ethy

l-( 2

-hyd

roxy

ethy

l)am

ine

N-N

itro

som

ethy

l-2-

hydr

oxyp

ropy

lam

ine

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

norn

icot

ine-

1-N

-oxi

de

N-N

itro

sopi

peri

dine

z P

hena

cetin

z Ph

enyl

glyc

idyl

ethe

r1

2-Pr

opyl

ene

oxid

ez V

inyl

acet

atez

Vin

ylch

lori

dez

Ner

vous

Mou

se3

13-

But

adie

nez

N-N

itros

odim

ethy

lam

inez

Pro

carb

azin

eH

Clz

syst

emR

at21

Acr

ylam

ide

Acr

ylon

itril

eB

rom

oeth

anez

Chl

oram

buci

lz 1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

eC

yclo

phos

pham

idez

1-E

thyl

-1-n

itros

oure

aE

thyl

eneo

xide

z 1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

eaG

lu-P

-1z

Glu

-P-2

z G

lyci

dolz

R(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

S(

) -2-

Met

hyl-

N-n

itro

sopi

peri

dine

M

ethy

lnit

ram

ine

N-N

itros

o-N

-met

hylu

reaz

N-N

itros

odie

than

olam

ine

1-P

heny

l-3

3-di

met

hyltr

iaze

neP

roca

rbaz

ine

HC

lz P

ropa

nesu

ltone

Vin

ylch

lori

dez

Ora

lcav

ityc

Ham

ster

4A

ceta

ldeh

yde

Nitr

oso-

26-

dim

ethy

lmor

phol

ine

N-N

itros

omor

phol

ine

N-N

itro

sopi

peri

dine

z

Mou

se3

N-N

itros

ohex

amet

hyle

neim

ine

12

3-T

rich

loro

prop

anez

Vin

ylac

etat

ez

Rat

32A

cryl

amid

eA

cryl

onitr

ile

Ben

zene

z 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

CI

dir

ectb

lue

15C

Id

irec

tblu

e21

8z C

hlor

opre

nez

3-D

iazo

tyra

min

eH

Cl

12-

Dib

rom

o-3-

chlo

ropr

opan

ez 3

3-D

imet

hoxy

benz

idin

e2H

Cl

33

-Dim

ethy

lben

zidi

ne2

HC

lz D

imet

hylv

inyl

chlo

ride

z D

initr

osoh

omop

iper

azin

eG

lyci

dolz

IQz

MeA

-a-C

acet

atez

N-N

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

hydr

oxyp

ropy

lam

ine

Nit

roso

-23

-dih

ydro

xypr

opyl

-2-

oxop

ropy

lam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

itro

soam

ylur

etha

nN

-Nitr

osod

ieth

ylam

ine

Nit

roso

ethy

lure

than

N

itros

ohep

tam

ethy

lene

imin

e1-

Nitr

osoh

ydan

toin

N-N

itros

omet

hyl(

2-ox

opro

pyl)

amin

eN

-Nit

roso

thia

ldin

eN

-Nitr

osot

hiom

orph

olin

eC

Ia

cid

red

114

23

78-

Tetr

achl

orod

iben

zo-p

-dio

xinz

Tolu

eney

12

3-T

rich

loro

prop

anez

Xyl

ene

mix

ture

( m-x

ylen

eo-

xyle

nep

-xyl

ene)

Ova

ryM

ouse

10B

enze

nez

13-

But

adie

nez

Die

thyl

stil

best

rolz

N-M

ethy

lola

cryl

amid

ey 5-

Nitr

o-2-

fura

ldeh

yde

sem

icar

bazo

nez

5-N

itroa

cena

phth

enez

1-[(

5-N

itro

furf

uryl

iden

e)am

ino]

hyda

ntoi

nz P

heno

lpht

hale

inz

Tam

oxif

enci

trat

ez 4-

Vin

ylcy

cloh

exen

ePa

ncre

asH

amst

er3

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

itro

so-2

6-d

imet

hylm

orph

olin

eN

itro

so-2

-oxo

prop

ylet

hano

lam

ine

Mon

key

1U

reth

anez

Rat

222-

Am

ino-

5-ni

trop

heno

ly 1-

( Am

inom

ethy

l)cy

cloh

exan

eace

ticac

idA

zase

rine

But

ylbe

nzyl

phth

alat

ey C

hlor

endi

cac

idz

Cin

nam

ylan

thra

nila

tez

Clo

bra

tey

Dic

hlor

vosz

Eth

ylal

coho

ly H

ydro

chlo

ro

uoro

carb

on12

3IQ

HC

lM

alon

alde

hyde

sod

ium

saltz

MeA

-a-C

acet

atez

2-M

erca

ptob

enzo

thia

zole

y M

ethy

lclo

fena

pate

z N

-(N

-Met

hyl-

N-n

itros

ocar

bam

oyl)

-l-o

rnit

hine

4-(

Met

hyln

itro

sam

ino)

-1-(

3-py

ridy

l)-1

-but

anol

4-(

Met

hyln

itros

amin

o)-1

-( 3

-pyr

idyl

) -1-

( but

anon

e)N

afen

opin

Nitr

ofen

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)z1

23

-Tri

chlo

ropr

opan

ez

Peri

tone

alM

ouse

8B

is-1

2-(

chlo

rom

etho

xy) e

than

eB

is-1

4-(

chlo

rom

etho

xy) -

p-xy

lene

Bis

-(ch

loro

met

hyl)

ethe

rz C

hlor

opre

nez

tran

s-1

4-D

ichl

orob

uten

e-2

cavi

tyD

imet

hylc

arba

myl

chlo

ride

Phe

noxy

benz

amin

eH

Clz

Tri

s-1

23-

( chl

orom

etho

xy) p

ropa

neR

at22

Acr

onyc

ine

Acr

ylam

ide

Act

inom

ycin

DA

nili

neH

Cly

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

rom

ate

pota

ssiu

mz

Chl

oroz

otoc

in

Cyt

embe

nay

Dap

sone

y 1

2-D

ibro

moe

than

ez D

ibro

mom

anni

tolz

33

-Dim

ethy

lben

zidi

ne2

HC

lz 1

4-D

ioxa

nez

Eth

ylen

eox

idez

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz M

elph

alan

z N

-Met

hyl-

N4

-din

itros

oani

line

Mit

omyc

in-C

N-N

itro

so-2

24

-tri

met

hyl-

12-

dihy

droq

uino

line

poly

mer

Ph

enox

yben

zam

ine

HC

lz o-

Tolu

idin

eH

Clz

( Con

tinue

don

next

page

)

645

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Pitu

itar

ygl

and

Mou

se8

Die

thyl

stil

best

rolz

Eno

vid

Eth

ylen

eth

iour

eaz

Iodi

nate

dgl

ycer

olz

Isop

rene

Nor

lest

rinz

Pro

pylt

hiou

raci

lz Z

eara

leno

ney

Rat

73-

Am

inot

riaz

olez

12-

Dib

rom

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylal

coho

ly 2-

Mer

capt

oben

zoth

iazo

ley

Met

roni

dazo

lez

Nor

lest

rinz

Pros

tate

Rat

4C

adm

ium

chlo

ride

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

PhIP

HC

lz

Skin

Ham

ster

2U

reth

anez

Vin

ylch

lori

dez

Mou

se5

5-A

zacy

tidin

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Chl

orop

rene

z G

lyci

dolz

Thi

o-te

paz

Rat

332-

Ace

tyla

min

ouo

rene

z 3-

Am

ino-

9-et

hylc

arba

zole

mix

ture

z 1-

Azo

xypr

opan

e2-

Azo

xypr

opan

eB

enze

nez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

ol

tech

nica

lgra

dez

CI

dir

ectb

lue

15C

arbo

xym

ethy

lnitr

osou

rea

24-

Dia

min

oani

sole

sulf

atez

Dib

rom

odul

cito

lz D

ibro

mom

anni

tolz

Dim

etho

xane

2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

Dim

ethy

lvin

ylch

lori

dez

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

26-

dini

trot

olue

ne)z

1-E

thyl

nitr

oso-

3-( 2

-hyd

roxy

ethy

l)-u

rea

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz 1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

IQ

z L

asio

carp

ine

MeI

Qxz

N-(

N-M

ethy

l-N

-nitr

osoc

arba

moy

l)-l

-orn

ithi

ne

5-N

itro-

o-an

isid

inez

CI

aci

dre

d11

4p-

Ros

anili

neH

Clz

Thi

o-te

paz

Thi

oure

ay V

inyl

chlo

ride

z F

Damp

Cvi

olet

no1

y

Smal

lint

esti

neM

ouse

6C

apta

folz

Cap

tanz

N-E

thyl

-N-n

itro

-N-n

itro

sogu

anid

ine

Hyd

roge

npe

roxi

deN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-(

Tri

chlo

rom

ethy

lthi

o)ph

thal

imid

eM

onke

y1

Ure

than

ez

Rat

29A

cryl

onitr

ile

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is( 2

3-d

ibro

mop

ropy

l)ph

osph

ate

mag

nesi

umsa

lt4

-Bis

( 2-h

ydro

xyet

hyl)

amin

o-2-

( 5-n

itro

-2-t

hien

yl) q

uina

zolin

eC

Id

irec

tblu

e15

Car

boxy

met

hyln

itros

oure

a1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

e2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro

-2-f

uryl

)py

rim

idin

etr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-[

2-( 5

-nit

ro-2

-fur

yl) v

inyl

] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

Z-E

thyl

-ON

N-a

zoxy

met

hane

1-E

thyl

-1-n

itros

oure

aFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lu-P

-1z

Glu

-P-2

z IQ

z L

asio

carp

ine

N-M

ethy

l-N

-nitr

o-N

-nitr

osog

uani

dine

z N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez N

-Nitr

oso-

N-i

sobu

tylu

rea

3-N

itro

so-2

-oxa

zoli

dino

neN

itro

soet

hylu

reth

ane

PhI

PH

Clz

Pro

pane

sulto

neQ

uerc

etin

y C

Ia

cid

red

114

Trp

-P-2

acet

atez

Sple

enR

at7

Ani

line

HC

ly A

zobe

nzen

ey p-

Chl

oroa

nili

neH

Clz

Dap

sone

y o-

Nitr

osot

olue

neD

ampC

red

no9

y o-

Tolu

idin

eH

Clz

Stom

ach

Ham

ster

18A

F-2z

14-

Din

itros

o-2

6-di

met

hylp

iper

azin

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z H

ydra

zine

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] a

ceta

mid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

N-N

itro

so-2

3-d

ihyd

roxy

prop

yl-2

-hyd

roxy

prop

ylam

ine

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

-Nitr

oso-

ethy

l-2-

oxop

ropy

lure

aN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

itros

o-5-

met

hylo

xazo

lidon

eN

-Nit

roso

-N-m

ethy

lure

than

N-N

itros

o-1

3-ox

azol

idin

eN

-Nit

roso

-2-p

heny

leth

ylur

ea1

-Nit

roso

-34

5-t

rim

ethy

lpip

eraz

ine

Ure

than

ez V

inyl

chlo

ride

z

Mou

se63

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eA

ciu

orfe

nA

F-2

z 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

tran

s-5-

Am

ino-

3[2-

( 5-n

itro-

2-fu

ryl)

viny

l] -1

24-

oxad

iazo

leA

reco

line

HC

lB

enza

ldeh

ydey

Ben

zofu

ranz

Ben

zotr

ichl

orid

eB

enzy

lace

tate

y B

enzy

lchl

orid

ey B

rom

oeth

anol

13

-But

adie

nez

But

ylat

edhy

drox

yani

sole

z 1

1-di

-N-B

utyl

hydr

azin

eC

affe

icac

idz

Cap

tafo

lz C

arba

zole

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z3

-(C

hlor

omet

hyl)

pyri

dine

HC

lz C

hlor

opre

nez

2-C

hlor

opro

pana

l1-

Chl

orop

rope

neC

ypro

tero

neac

etat

e1

1-D

ially

lhyd

razi

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dic

hlor

vosz

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez D

imet

hylv

inyl

chlo

ride

z D

init

roso

pipe

razi

neE

stra

diol

mus

tard

y E

thyl

acry

late

z Fo

rmic

acid

2-[ 4

-( 5

-nit

ro-2

-fur

yl) -

2-th

iazo

lyl] h

ydra

zide

z G

lyci

dolz

2-H

ydra

zino

-4-(

5-ni

tro-

2-fu

ryl)

thia

zole

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

ICI

1628

46z

IQz

Isop

rene

Lov

asta

tin

MeI

Q1

-Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m3

-(5-

Nitr

o-2-

fury

l)-

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] f

orm

amid

ez N

-Nit

roso

-N

-met

hylu

reaz

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

hexa

met

hyle

neim

ine

N-N

itros

opip

erid

inez

b-P

ropi

olac

tone

z Se

sam

olz

Sty

rene

oxid

ez Te

lone

IIt

echn

ical

grad

ez N

-(T

rich

loro

met

hylth

io) p

htha

limid

e1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uo

ro-N

-[4-

( 5-n

itro

-2-f

uryl

) -2-

thia

zoly

l]ac

etam

idez

Tri

ur

alin

tec

hnic

algr

adey

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylac

etat

ez

Rat

85A

ceto

ne[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zone

1-A

ceto

xysa

frol

ey A

cryl

onitr

ile

1-A

llyl

-1-n

itro

sour

ea2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-ox

adia

zole

2-

Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-4-

( 5-n

itro

-2-f

uryl

) thi

azol

ez 1-

Am

yl-1

-nit

roso

urea

Ari

stol

ochi

cac

id

sodi

umsa

lt( 7

7A

AI

21

AA

II)

Ben

zene

z B

enzo

( a) p

yren

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

BL

-634

1H

Cl

N-n

-But

yl-N

-nitr

osou

rea

But

ylat

edhy

drox

yani

sole

z b

-But

yrol

acto

neC

affe

icac

idz

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z4

-Chl

oro-

o-ph

enyl

ened

iam

inez

Chl

oro

uoro

met

hane

3-

( Chl

orom

ethy

l)py

ridi

neH

Clz

Cip

rob

rate

z C

upfe

rron

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez 2

5-D

imet

hoxy

-4-a

min

osti

lben

ez D

imet

hylh

ydro

gen

phos

phit

ey 4

6-D

imet

hyl-

2-( 5

-nit

ro-2

-fu

ryl)

pyri

mid

ine

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lvin

ylch

lori

dez

Epi

chlo

rohy

drin

y E

thyl

acry

late

z E

thyl

ene

oxid

ez 2-

Flu

oroe

thyl

-nitr

osou

rea

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-

nitr

osou

reaz

1-( 3

-Hyd

roxy

prop

yl) -

1-ni

tros

oure

a1

-Hyd

roxy

safr

olez

ICI

1628

46z

Lox

tidin

eL

upit

idin

e3H

Cl

Mer

curi

cch

lori

dey

3-M

etho

xyca

tech

ol4

-Met

hoxy

phen

olN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-M

ethy

l-N

-nit

roso

benz

amid

e4-

Met

hylc

atec

hol

Met

hyln

itro

socy

anam

ide

3-( 5

-Nit

ro-2

-fur

yl) -

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

4-( 5

-Nit

ro-2

-fur

yl) t

hiaz

ole

2-N

itro

uo

rene

8-N

itro

quin

olin

eN

itro

so-B

aygo

nN

-Nit

roso

-23

-dih

ydro

xypr

opyl

-2-h

ydro

xypr

opyl

amin

eN

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

oxop

ropy

lam

ine

1-N

itro

so-3

5-d

imet

hyl-

4-be

nzoy

lpip

eraz

ine

N-N

itro

so-N

-met

hyl-

N-d

odec

ylam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itro

so-N

-met

hylu

reaz

Nit

roso

-12

36

-tet

rahy

drop

yrid

ine

N-N

itro

sobe

nzth

iazu

ron

Nitr

osod

ibut

ylam

inez

N-N

itros

odie

thyl

amin

eN

-Nit

roso

ephe

drin

eN

itros

oeth

ylur

etha

nO

mep

razo

ley

Phen

acet

inz

Piv

alol

acto

ney

b-P

ropi

olac

tone

z N

-Pro

pyl-

N-n

itro

-N-n

itro

sogu

anid

ine

12-

Pro

pyle

neox

idez

Ses

amol

z St

yren

eox

idez

Sulf

alla

tez

Telo

neII

tec

hnic

algr

adez

12

3-T

rich

loro

prop

anez

24

6-T

rim

ethy

lani

line

HC

lz

646

Subc

utan

eous

Mou

se4

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

2-D

ibro

moe

than

ez N

2-c

-Glu

tam

yl-p

-hyd

razi

nobe

nzoi

cac

idG

lyci

dolz

tissu

eR

at13

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ichl

oroe

than

ez D

imet

hoxa

ne1

4-D

ioxa

nez

MeA

-a-C

acet

atez

44

-Met

hyle

ne-b

is( 2

-met

hyla

nili

ne)

o-N

itro

soto

luen

ep-

Ros

anili

neH

Clz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 2

45-

Tri

met

hyla

nilin

eH

Clz

25-

Xyl

idin

eH

Clz

Test

isM

ouse

4D

ieth

ylst

ilbe

stro

lz Fi

nast

erid

eR

eser

pine

z Ta

mox

ifen

citr

atez

Rat

185-

Aza

cytid

inez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

3-B

utad

iene

z N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

Cad

miu

mch

lori

de

2-C

hlor

o-1

11-

tri

uoro

etha

ne1

1-D

ichl

oro-

1-u

oroe

than

eH

ydro

chlo

rou

oroc

arbo

n12

3M

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z M

etro

nida

zole

z N

-Nit

roso

dim

ethy

lam

inez

Oxo

linic

acid

y SD

Z20

0-11

01

11

2-Te

tra

uoro

etha

ney

Tri

chlo

roet

hyle

nez

Tri

nitr

ogly

ceri

nV

inyl

chlo

ride

z

Thy

roid

glan

dH

amst

er4

Hex

achl

orob

enze

nez

Hyd

razi

nez

Met

hylt

hiou

raci

lU

reth

anez

Mou

se18

3-A

min

o-4-

etho

xyac

etan

ilide

y H

Cbl

ueno

1z

tert

-But

ylal

coho

lz C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

24

-Dia

min

oani

sole

sulf

atez

Die

thyl

stil

best

rolz

Dox

ylam

ine

succ

inat

ez E

thio

nam

idey

Eth

ylen

eth

iour

eaz

44

-Met

hyle

nedi

anil

ine

2HC

lz 1

5-N

apht

hale

nedi

amin

ez N

itrob

enze

nez

Oxa

zepa

my

44

-Oxy

dian

iline

z C

Ip

igm

entr

ed3z

Sulf

amet

hazi

ne2

37

8-T

etra

chlo

rodi

benz

o-p-

diox

inz

44

-Thi

odia

nilin

ez

Rat

33A

cryl

amid

e3-

Am

inot

riaz

olez

o-A

nisi

dine

HC

lz B

emit

radi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

Chl

orop

rene

z 2

4-D

iam

inoa

niso

lesu

lfat

ez N

N-D

ieth

ylth

iour

eay

1-E

thyl

-1-n

itro

sour

ea

Eth

ylen

eth

iour

eaz

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Flu

vast

atin

Gly

cido

lz Io

dina

ted

glyc

erol

z Is

obut

eney

Mal

onal

dehy

des

odiu

msa

ltz

Met

him

azol

e4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Mir

exp

hoto

-N

itro

benz

enez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

44

-Oxy

dian

iline

z Pr

opyl

thio

urac

ilz p-

Ros

anil

ine

HC

lz 2

37

8-Te

trac

hlor

odib

enzo

-p-d

ioxi

nz 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tri

met

hylt

hiou

reay

Vin

ylac

etat

ez Z

inc

dim

ethy

ldith

ioca

rbam

atez

Uri

nary

blad

der

Dog

23

3-D

ichl

orob

enzi

dine

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nilin

e)H

amst

er3

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

acet

amid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

Mou

se12

2-A

cety

lam

ino

uore

nez

4-A

min

odip

heny

l2-

Am

inod

iphe

nyle

neox

ide

o-A

nisi

dine

HC

lz 4-

Chl

oro-

4-a

min

odip

heny

leth

erz

p-C

resi

dine

z 4-

Eth

ylsu

lpho

nyln

apht

hale

ne-1

-sul

fona

mid

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hena

cetin

z Te

lone

IIt

echn

ical

grad

ez U

raci

lz

Mon

key

12-

Nap

hthy

lam

inez

Rat

49A

ceta

min

ophe

nz A

llyli

soth

iocy

anat

ey 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

4-A

min

o-2-

nitr

ophe

noly

11-A

min

ound

ecan

oic

acid

y o-

Ani

sidi

neH

Clz

Ari

stol

ochi

cac

ids

odiu

msa

lt( 7

7A

AI

21

AA

II)

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

ispe

rse

blue

1y N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

4-C

hlor

o-o-

phen

ylen

edia

min

ez m

-Cre

sidi

ney

p-C

resi

dine

z C

yclo

phos

pham

idez

Die

thyl

ene

glyc

olD

imet

hyla

rsin

icac

idy

Fose

tylA

lIQ

HC

lM

eA-a

-Cac

etat

ez M

elam

iney

2-M

etho

xy-3

-am

inod

iben

zofu

ran

2-N

apht

hyla

min

ez N

itril

otri

acet

icac

idz

Nitr

ilot

riac

etic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez o-

Nitr

oani

sole

z N

-Nitr

oso-

N-m

ethy

l-N

-dod

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

l-N

-tet

rade

cyla

min

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itro

sodi

phen

ylam

iney

o-N

itros

otol

uene

N-O

xydi

ethy

lene

thio

carb

amyl

-N-o

xydi

ethy

lene

sulf

enam

ide

Phe

nace

tinz

Phen

azon

eo-

Phen

ylph

enat

eso

dium

y o-

Phen

ylph

enol

y P

otas

sium

bica

rbon

ate

Purp

urin

Que

rcet

iny

p-Q

uino

nedi

oxim

ey Sa

ccha

rin

sodi

umy

Sali

cyla

zosu

lfap

yrid

inez

o-To

luen

esul

fona

mid

eo-

Tolu

idin

eH

Clz

Trp

-P-2

acet

atez

Ura

cilz

Ute

rus

Ham

ster

1N

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aM

ouse

12B

rom

oeth

anez

Chl

oroe

than

ey D

acar

bazi

nez

12-

Dic

hlor

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylen

eox

idez

Gly

cido

lz ( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Proc

arba

zine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez T

rim

ethy

lpho

spha

tey

Vin

ylac

etat

ez

Rat

26A

cryl

amid

e1-

Ally

l-1-

nitr

osou

rea

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

myl

-1-n

itros

oure

aA

traz

iney

CI

dir

ectb

lue

15B

rom

ocri

ptin

em

esyl

atey

N-n

-But

yl-N

-nit

roso

urea

Cal

cium

valp

roat

eC

apta

nz 2-

Chl

oro-

11

1-tr

iuo

roet

hane

Dac

arba

zine

z D

amin

ozid

ez 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

lD

imet

hyla

min

oeth

ylni

tros

oeth

ylur

ean

itri

tesa

lt1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

ICR

F-1

59z

Isop

hosp

ham

idez

15-

Nap

htha

lene

diam

inez

Nit

robe

nzen

ez N

orle

stri

nz 4

4-T

hiod

iani

linez

Vin

ylac

etat

ez

Vag

ina

Mou

se1

AZ

Tz

Rat

2A

ZT

z N

-n-B

utyl

-N-n

itro

sour

ea( C

ontin

ued

onne

xtpa

ge)

647

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Vas

cula

rsy

stem

Ham

ster

91

2-D

imet

hylh

ydra

zine

2H

Cl

Gly

cido

lz H

exac

hlor

oben

zene

z N

-Nit

roso

-eth

yl-2

-oxo

prop

ylur

eaN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

-Nitr

oso-

oxop

ropy

lchl

oroe

thyl

urea

N-N

itro

so-o

xopr

opyl

urea

N-N

itros

o-2-

phen

ylet

hylu

rea

Vin

ylch

lori

dez

Mou

se59

A-a

-CN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-ph

enyl

hydr

azin

eA

llyl

hydr

azin

eH

Cl

Are

colin

eH

Cl

Aza

thio

prin

eB

enzi

dine

2H

Cl

2-B

iphe

nyla

min

eH

Cly

13-

But

adie

nez

Cap

tafo

lz C

arba

myl

hydr

azin

eH

Cl

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 1-

Chl

oro-

4-ni

trob

enze

ney

5-C

hlor

o-o-

tolu

idin

ey 4-

Chl

oro-

o-to

luid

ine

HC

ly p-

Chl

oroa

nilin

eH

Clz

Chl

orop

rene

z C

upfe

rron

z D

acar

bazi

nez

Dam

inoz

idez

24-

Dia

min

otol

uene

2H

Clz

12-

Dib

rom

oeth

anez

Dif

talo

ne7

12-

Dim

ethy

lben

z(a)

anth

race

ne1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylhy

draz

ine

HC

lG

lu-P

-1z

Glu

-P-2

z p-

Hyd

razi

nobe

nzoi

cac

idH

Cl

1-H

ydro

xysa

frol

ez Is

opre

neM

eA-a

-Cac

etat

ez N

-Met

hyl-

N-f

orm

ylhy

draz

ine

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

Mic

hler

rsquoske

tone

z 5-

Nitr

o-o-

tolu

idin

ey N

itro

fenz

N-N

itros

o-N

-met

hylu

reaz

Pent

achl

oroa

niso

lez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y2

34

56

-Pen

tach

loro

phen

olt

echn

ical

grad

ez n-

Pen

tylh

ydra

zine

HC

lPh

enyl

ethy

lhyd

razi

nesu

lfat

ePh

enyl

hydr

azin

eH

Cl

Ster

igm

atoc

ysti

nz Te

tra

uoro

ethy

lene

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)zo

-Tol

uidi

neH

Clz

24

6-T

rich

loro

anil

iney

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nili

neH

Clz

Ure

than

ez V

inyl

carb

amat

eV

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y 2

5-X

ylid

ine

HC

lz

Mon

key

2A

ato

xin

B1y

Ure

than

ez

Rat

32A

nilin

eH

Cly

Azo

benz

eney

Ben

zene

z C

livor

ine

Cup

ferr

onz

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neI

QH

Cl

Las

ioca

rpin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line)

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-N

itros

o-( 2

-hyd

roxy

prop

yl) -

( 2-h

ydro

xyet

hyl)

amin

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nitr

osob

is( 2

-oxo

prop

yl) a

min

eN

-Nit

roso

diet

hano

lam

ine

N-N

itro

sodi

ethy

lam

ine

N-N

itros

odim

ethy

lam

inez

N-N

itros

omet

hyl-

( 2-t

osyl

oxye

thyl

) am

ine

N-N

itros

omor

phol

ine

N-N

itro

sopy

rrol

idin

ez Pe

tasi

teni

neS

teri

gmat

ocys

tinz

Sym

phyt

ine

Tetr

auo

roet

hyle

nez

o-To

luid

ine

HC

lz T

rp-P

-2ac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

aT

here

was

nore

port

edta

rget

site

in1

spec

ies

( rat

sor

mic

e)fo

r5

chem

ical

sw

ithsu

pers

crip

tsb

utth

ech

emic

alw

asev

alua

ted

byth

epu

blis

hed

auth

oras

aca

rcin

ogen

ald

rinz

diel

drin

z N

-nit

roso

pyrr

olid

inez

23

45

6-pe

ntac

hlor

ophe

nol

( Dow

icid

eE

C-7

)ya

ndur

etha

nez

bN

asal

cavi

tyin

clud

estis

sues

ofth

eno

sen

asal

turb

inat

esp

aran

asal

sinu

ses

and

trac

hea

c Ora

lcav

ityin

clud

estis

sues

ofth

em

outh

oro

phar

ynx

phar

ynx

and

lary

nx

Ach

emic

alis

liste

dun

der

each

orga

nev

alua

ted

aspo

sitiv

ein

anex

peri

men

tin

that

spec

ies

byat

leas

t1au

thor

The

refo

rea

chem

ical

may

beli

sted

unde

rse

vera

ltar

geto

rgan

san

dev

ery

chem

ical

liste

din

the

tabl

eis

posi

tive

inat

leas

t1sp

ecie

sIn

orde

rto

com

pare

resu

ltsin

rats

and

mic

esy

mbo

lsfo

llow

chem

ical

ste

sted

inbo

thsp

ecie

sa

zin

dica

tes

that

the

chem

ical

ispo

sitiv

eat

som

esi

tein

both

spec

ies

and

ay

indi

cate

sth

atit

was

test

edin

both

butp

ositi

vein

only

1a

Nth

enu

mbe

rof

chem

ical

sw

ithat

leas

t1po

sitiv

ete

stat

that

site

inth

atsp

ecie

sB

ecau

sem

any

chem

ical

sin

duce

tum

ors

atm

ore

than

1si

tein

agi

ven

spec

ies

man

ych

emic

als

appe

arm

ore

than

once

inth

eta

ble

648

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649

species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters

RESULTS IN RATS AND MICE

For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens

TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database

Chemicals evaluated as carcinogenic in

Rats Mice

All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)

Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2

a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not

b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats

All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical

to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included

The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site

Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 8: Compendium of Chemical Carcinogens by Target Organ - Toxnet

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Pitu

itar

ygl

and

Mou

se8

Die

thyl

stil

best

rolz

Eno

vid

Eth

ylen

eth

iour

eaz

Iodi

nate

dgl

ycer

olz

Isop

rene

Nor

lest

rinz

Pro

pylt

hiou

raci

lz Z

eara

leno

ney

Rat

73-

Am

inot

riaz

olez

12-

Dib

rom

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylal

coho

ly 2-

Mer

capt

oben

zoth

iazo

ley

Met

roni

dazo

lez

Nor

lest

rinz

Pros

tate

Rat

4C

adm

ium

chlo

ride

N-N

itros

obis

( 2-h

ydro

xypr

opyl

) am

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

PhIP

HC

lz

Skin

Ham

ster

2U

reth

anez

Vin

ylch

lori

dez

Mou

se5

5-A

zacy

tidin

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Chl

orop

rene

z G

lyci

dolz

Thi

o-te

paz

Rat

332-

Ace

tyla

min

ouo

rene

z 3-

Am

ino-

9-et

hylc

arba

zole

mix

ture

z 1-

Azo

xypr

opan

e2-

Azo

xypr

opan

eB

enze

nez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

ol

tech

nica

lgra

dez

CI

dir

ectb

lue

15C

arbo

xym

ethy

lnitr

osou

rea

24-

Dia

min

oani

sole

sulf

atez

Dib

rom

odul

cito

lz D

ibro

mom

anni

tolz

Dim

etho

xane

2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

l3

3-D

imet

hylb

enzi

dine

2H

Clz

Dim

ethy

lvin

ylch

lori

dez

24-

Din

itro

tolu

ene

( con

tain

ing

10-

15

26-

dini

trot

olue

ne)z

1-E

thyl

nitr

oso-

3-( 2

-hyd

roxy

ethy

l)-u

rea

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Gly

cido

lz 1-

( 2-H

ydro

xyet

hyl)

-nit

roso

-3-e

thyl

urea

IQ

z L

asio

carp

ine

MeI

Qxz

N-(

N-M

ethy

l-N

-nitr

osoc

arba

moy

l)-l

-orn

ithi

ne

5-N

itro-

o-an

isid

inez

CI

aci

dre

d11

4p-

Ros

anili

neH

Clz

Thi

o-te

paz

Thi

oure

ay V

inyl

chlo

ride

z F

Damp

Cvi

olet

no1

y

Smal

lint

esti

neM

ouse

6C

apta

folz

Cap

tanz

N-E

thyl

-N-n

itro

-N-n

itro

sogu

anid

ine

Hyd

roge

npe

roxi

deN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-(

Tri

chlo

rom

ethy

lthi

o)ph

thal

imid

eM

onke

y1

Ure

than

ez

Rat

29A

cryl

onitr

ile

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez B

is( 2

3-d

ibro

mop

ropy

l)ph

osph

ate

mag

nesi

umsa

lt4

-Bis

( 2-h

ydro

xyet

hyl)

amin

o-2-

( 5-n

itro

-2-t

hien

yl) q

uina

zolin

eC

Id

irec

tblu

e15

Car

boxy

met

hyln

itros

oure

a1-

( 4-C

hlor

ophe

nyl)

-1-p

heny

l-2-

prop

ynyl

carb

amat

e2

5-D

imet

hoxy

-4-a

min

ostil

bene

z 3

3-D

imet

hoxy

benz

idin

e2H

Cl

46-

Dim

ethy

l-2-

( 5-n

itro

-2-f

uryl

)py

rim

idin

etr

ans-

2-[(

Dim

ethy

lam

ino)

met

hylim

ino]

-5-[

2-( 5

-nit

ro-2

-fur

yl) v

inyl

] -1

34-

oxad

iazo

le3

3-D

imet

hylb

enzi

dine

2H

Clz

Z-E

thyl

-ON

N-a

zoxy

met

hane

1-E

thyl

-1-n

itros

oure

aFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z G

lu-P

-1z

Glu

-P-2

z IQ

z L

asio

carp

ine

N-M

ethy

l-N

-nitr

o-N

-nitr

osog

uani

dine

z N

-[5-

( 5-N

itro-

2-fu

ryl)

-13

4-t

hiad

iazo

l-2-

yl] a

ceta

mid

ez N

-Nitr

oso-

N-i

sobu

tylu

rea

3-N

itro

so-2

-oxa

zoli

dino

neN

itro

soet

hylu

reth

ane

PhI

PH

Clz

Pro

pane

sulto

neQ

uerc

etin

y C

Ia

cid

red

114

Trp

-P-2

acet

atez

Sple

enR

at7

Ani

line

HC

ly A

zobe

nzen

ey p-

Chl

oroa

nili

neH

Clz

Dap

sone

y o-

Nitr

osot

olue

neD

ampC

red

no9

y o-

Tolu

idin

eH

Clz

Stom

ach

Ham

ster

18A

F-2z

14-

Din

itros

o-2

6-di

met

hylp

iper

azin

eFo

rmic

acid

2-[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zide

z H

ydra

zine

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] a

ceta

mid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

N-N

itro

so-2

3-d

ihyd

roxy

prop

yl-2

-hyd

roxy

prop

ylam

ine

Nitr

oso-

23-

dihy

drox

ypro

pyl-

2-ox

opro

pyla

min

eN

-Nitr

oso-

ethy

l-2-

oxop

ropy

lure

aN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

itros

o-5-

met

hylo

xazo

lidon

eN

-Nit

roso

-N-m

ethy

lure

than

N-N

itros

o-1

3-ox

azol

idin

eN

-Nit

roso

-2-p

heny

leth

ylur

ea1

-Nit

roso

-34

5-t

rim

ethy

lpip

eraz

ine

Ure

than

ez V

inyl

chlo

ride

z

Mou

se63

Ace

tald

ehyd

em

ethy

lfor

myl

hydr

azon

eA

ciu

orfe

nA

F-2

z 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

tran

s-5-

Am

ino-

3[2-

( 5-n

itro-

2-fu

ryl)

viny

l] -1

24-

oxad

iazo

leA

reco

line

HC

lB

enza

ldeh

ydey

Ben

zofu

ranz

Ben

zotr

ichl

orid

eB

enzy

lace

tate

y B

enzy

lchl

orid

ey B

rom

oeth

anol

13

-But

adie

nez

But

ylat

edhy

drox

yani

sole

z 1

1-di

-N-B

utyl

hydr

azin

eC

affe

icac

idz

Cap

tafo

lz C

arba

zole

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z3

-(C

hlor

omet

hyl)

pyri

dine

HC

lz C

hlor

opre

nez

2-C

hlor

opro

pana

l1-

Chl

orop

rope

neC

ypro

tero

neac

etat

e1

1-D

ially

lhyd

razi

ne1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

Dic

hlor

vosz

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez D

imet

hylv

inyl

chlo

ride

z D

init

roso

pipe

razi

neE

stra

diol

mus

tard

y E

thyl

acry

late

z Fo

rmic

acid

2-[ 4

-( 5

-nit

ro-2

-fur

yl) -

2-th

iazo

lyl] h

ydra

zide

z G

lyci

dolz

2-H

ydra

zino

-4-(

5-ni

tro-

2-fu

ryl)

thia

zole

z N

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

ICI

1628

46z

IQz

Isop

rene

Lov

asta

tin

MeI

Q1

-Met

hyl-

14-

dihy

dro-

7-[ 2

-(5-

nitr

ofur

yl) v

inyl

] -4-

oxo-

18-

naph

thyr

idin

e-3-

carb

oxyl

ate

pota

ssiu

m3

-(5-

Nitr

o-2-

fury

l)-

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-[

4-( 5

-Nitr

o-2-

fury

l)-2

-thi

azol

yl] f

orm

amid

ez N

-Nit

roso

-N

-met

hylu

reaz

Nit

roso

dibu

tyla

min

ez N

-Nit

roso

hexa

met

hyle

neim

ine

N-N

itros

opip

erid

inez

b-P

ropi

olac

tone

z Se

sam

olz

Sty

rene

oxid

ez Te

lone

IIt

echn

ical

grad

ez N

-(T

rich

loro

met

hylth

io) p

htha

limid

e1

23-

Tri

chlo

ropr

opan

ez 2

22-

Tri

uo

ro-N

-[4-

( 5-n

itro

-2-f

uryl

) -2-

thia

zoly

l]ac

etam

idez

Tri

ur

alin

tec

hnic

algr

adey

Tri

s(2-

chlo

roet

hyl)

phos

phat

ez T

ris(

23-

dibr

omop

ropy

l)ph

osph

atez

Vin

ylac

etat

ez

Rat

85A

ceto

ne[ 4

-(5-

nitr

o-2-

fury

l)-2

-thi

azol

yl] h

ydra

zone

1-A

ceto

xysa

frol

ey A

cryl

onitr

ile

1-A

llyl

-1-n

itro

sour

ea2

-Am

ino-

5-( 5

-nit

ro-2

-fur

yl) -

13

4-ox

adia

zole

2-

Am

ino-

5-( 5

-nitr

o-2-

fury

l)-1

34

-thi

adia

zole

2-A

min

o-4-

( 5-n

itro

-2-f

uryl

) thi

azol

ez 1-

Am

yl-1

-nit

roso

urea

Ari

stol

ochi

cac

id

sodi

umsa

lt( 7

7A

AI

21

AA

II)

Ben

zene

z B

enzo

( a) p

yren

ez 2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bis

( 23

-dib

rom

opro

pyl)

phos

phat

em

agne

sium

salt

BL

-634

1H

Cl

N-n

-But

yl-N

-nitr

osou

rea

But

ylat

edhy

drox

yani

sole

z b

-But

yrol

acto

neC

affe

icac

idz

Cat

echo

lz 3-

Chl

oro-

2-m

ethy

lpro

pene

tec

hnic

algr

ade

( con

tain

ing

5di

met

hylv

inyl

chlo

ride

)z4

-Chl

oro-

o-ph

enyl

ened

iam

inez

Chl

oro

uoro

met

hane

3-

( Chl

orom

ethy

l)py

ridi

neH

Clz

Cip

rob

rate

z C

upfe

rron

z 1

2-D

ibro

mo-

3-ch

loro

prop

anez

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

Dig

lyci

dylr

esor

cino

leth

ert

echn

ical

grad

ez 2

5-D

imet

hoxy

-4-a

min

osti

lben

ez D

imet

hylh

ydro

gen

phos

phit

ey 4

6-D

imet

hyl-

2-( 5

-nit

ro-2

-fu

ryl)

pyri

mid

ine

tran

s-2-

[(D

imet

hyla

min

o)m

ethy

limin

o]-5

-[2-

( 5-n

itro

-2-f

uryl

) vin

yl] -

13

4-ox

adia

zole

Dim

ethy

lvin

ylch

lori

dez

Epi

chlo

rohy

drin

y E

thyl

acry

late

z E

thyl

ene

oxid

ez 2-

Flu

oroe

thyl

-nitr

osou

rea

Gly

cido

lz N

-Hex

ylni

tros

oure

a1-

Hyd

roxy

anth

raqu

inon

e1-

( 2-H

ydro

xyet

hyl)

-1-

nitr

osou

reaz

1-( 3

-Hyd

roxy

prop

yl) -

1-ni

tros

oure

a1

-Hyd

roxy

safr

olez

ICI

1628

46z

Lox

tidin

eL

upit

idin

e3H

Cl

Mer

curi

cch

lori

dey

3-M

etho

xyca

tech

ol4

-Met

hoxy

phen

olN

-Met

hyl-

N-n

itro-

N-n

itros

ogua

nidi

nez

N-M

ethy

l-N

-nit

roso

benz

amid

e4-

Met

hylc

atec

hol

Met

hyln

itro

socy

anam

ide

3-( 5

-Nit

ro-2

-fur

yl) -

imid

azo(

12-

a) p

yrid

inez

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

4-( 5

-Nit

ro-2

-fur

yl) t

hiaz

ole

2-N

itro

uo

rene

8-N

itro

quin

olin

eN

itro

so-B

aygo

nN

-Nit

roso

-23

-dih

ydro

xypr

opyl

-2-h

ydro

xypr

opyl

amin

eN

itros

o-2

3-di

hydr

oxyp

ropy

l-2-

oxop

ropy

lam

ine

1-N

itro

so-3

5-d

imet

hyl-

4-be

nzoy

lpip

eraz

ine

N-N

itro

so-N

-met

hyl-

N-d

odec

ylam

ine

Nitr

oso-

N-m

ethy

l-N

-(2-

phen

yl) e

thyl

amin

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itro

so-N

-met

hylu

reaz

Nit

roso

-12

36

-tet

rahy

drop

yrid

ine

N-N

itro

sobe

nzth

iazu

ron

Nitr

osod

ibut

ylam

inez

N-N

itros

odie

thyl

amin

eN

-Nit

roso

ephe

drin

eN

itros

oeth

ylur

etha

nO

mep

razo

ley

Phen

acet

inz

Piv

alol

acto

ney

b-P

ropi

olac

tone

z N

-Pro

pyl-

N-n

itro

-N-n

itro

sogu

anid

ine

12-

Pro

pyle

neox

idez

Ses

amol

z St

yren

eox

idez

Sulf

alla

tez

Telo

neII

tec

hnic

algr

adez

12

3-T

rich

loro

prop

anez

24

6-T

rim

ethy

lani

line

HC

lz

646

Subc

utan

eous

Mou

se4

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

2-D

ibro

moe

than

ez N

2-c

-Glu

tam

yl-p

-hyd

razi

nobe

nzoi

cac

idG

lyci

dolz

tissu

eR

at13

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ichl

oroe

than

ez D

imet

hoxa

ne1

4-D

ioxa

nez

MeA

-a-C

acet

atez

44

-Met

hyle

ne-b

is( 2

-met

hyla

nili

ne)

o-N

itro

soto

luen

ep-

Ros

anili

neH

Clz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 2

45-

Tri

met

hyla

nilin

eH

Clz

25-

Xyl

idin

eH

Clz

Test

isM

ouse

4D

ieth

ylst

ilbe

stro

lz Fi

nast

erid

eR

eser

pine

z Ta

mox

ifen

citr

atez

Rat

185-

Aza

cytid

inez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

3-B

utad

iene

z N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

Cad

miu

mch

lori

de

2-C

hlor

o-1

11-

tri

uoro

etha

ne1

1-D

ichl

oro-

1-u

oroe

than

eH

ydro

chlo

rou

oroc

arbo

n12

3M

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z M

etro

nida

zole

z N

-Nit

roso

dim

ethy

lam

inez

Oxo

linic

acid

y SD

Z20

0-11

01

11

2-Te

tra

uoro

etha

ney

Tri

chlo

roet

hyle

nez

Tri

nitr

ogly

ceri

nV

inyl

chlo

ride

z

Thy

roid

glan

dH

amst

er4

Hex

achl

orob

enze

nez

Hyd

razi

nez

Met

hylt

hiou

raci

lU

reth

anez

Mou

se18

3-A

min

o-4-

etho

xyac

etan

ilide

y H

Cbl

ueno

1z

tert

-But

ylal

coho

lz C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

24

-Dia

min

oani

sole

sulf

atez

Die

thyl

stil

best

rolz

Dox

ylam

ine

succ

inat

ez E

thio

nam

idey

Eth

ylen

eth

iour

eaz

44

-Met

hyle

nedi

anil

ine

2HC

lz 1

5-N

apht

hale

nedi

amin

ez N

itrob

enze

nez

Oxa

zepa

my

44

-Oxy

dian

iline

z C

Ip

igm

entr

ed3z

Sulf

amet

hazi

ne2

37

8-T

etra

chlo

rodi

benz

o-p-

diox

inz

44

-Thi

odia

nilin

ez

Rat

33A

cryl

amid

e3-

Am

inot

riaz

olez

o-A

nisi

dine

HC

lz B

emit

radi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

Chl

orop

rene

z 2

4-D

iam

inoa

niso

lesu

lfat

ez N

N-D

ieth

ylth

iour

eay

1-E

thyl

-1-n

itro

sour

ea

Eth

ylen

eth

iour

eaz

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Flu

vast

atin

Gly

cido

lz Io

dina

ted

glyc

erol

z Is

obut

eney

Mal

onal

dehy

des

odiu

msa

ltz

Met

him

azol

e4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Mir

exp

hoto

-N

itro

benz

enez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

44

-Oxy

dian

iline

z Pr

opyl

thio

urac

ilz p-

Ros

anil

ine

HC

lz 2

37

8-Te

trac

hlor

odib

enzo

-p-d

ioxi

nz 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tri

met

hylt

hiou

reay

Vin

ylac

etat

ez Z

inc

dim

ethy

ldith

ioca

rbam

atez

Uri

nary

blad

der

Dog

23

3-D

ichl

orob

enzi

dine

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nilin

e)H

amst

er3

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

acet

amid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

Mou

se12

2-A

cety

lam

ino

uore

nez

4-A

min

odip

heny

l2-

Am

inod

iphe

nyle

neox

ide

o-A

nisi

dine

HC

lz 4-

Chl

oro-

4-a

min

odip

heny

leth

erz

p-C

resi

dine

z 4-

Eth

ylsu

lpho

nyln

apht

hale

ne-1

-sul

fona

mid

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hena

cetin

z Te

lone

IIt

echn

ical

grad

ez U

raci

lz

Mon

key

12-

Nap

hthy

lam

inez

Rat

49A

ceta

min

ophe

nz A

llyli

soth

iocy

anat

ey 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

4-A

min

o-2-

nitr

ophe

noly

11-A

min

ound

ecan

oic

acid

y o-

Ani

sidi

neH

Clz

Ari

stol

ochi

cac

ids

odiu

msa

lt( 7

7A

AI

21

AA

II)

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

ispe

rse

blue

1y N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

4-C

hlor

o-o-

phen

ylen

edia

min

ez m

-Cre

sidi

ney

p-C

resi

dine

z C

yclo

phos

pham

idez

Die

thyl

ene

glyc

olD

imet

hyla

rsin

icac

idy

Fose

tylA

lIQ

HC

lM

eA-a

-Cac

etat

ez M

elam

iney

2-M

etho

xy-3

-am

inod

iben

zofu

ran

2-N

apht

hyla

min

ez N

itril

otri

acet

icac

idz

Nitr

ilot

riac

etic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez o-

Nitr

oani

sole

z N

-Nitr

oso-

N-m

ethy

l-N

-dod

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

l-N

-tet

rade

cyla

min

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itro

sodi

phen

ylam

iney

o-N

itros

otol

uene

N-O

xydi

ethy

lene

thio

carb

amyl

-N-o

xydi

ethy

lene

sulf

enam

ide

Phe

nace

tinz

Phen

azon

eo-

Phen

ylph

enat

eso

dium

y o-

Phen

ylph

enol

y P

otas

sium

bica

rbon

ate

Purp

urin

Que

rcet

iny

p-Q

uino

nedi

oxim

ey Sa

ccha

rin

sodi

umy

Sali

cyla

zosu

lfap

yrid

inez

o-To

luen

esul

fona

mid

eo-

Tolu

idin

eH

Clz

Trp

-P-2

acet

atez

Ura

cilz

Ute

rus

Ham

ster

1N

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aM

ouse

12B

rom

oeth

anez

Chl

oroe

than

ey D

acar

bazi

nez

12-

Dic

hlor

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylen

eox

idez

Gly

cido

lz ( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Proc

arba

zine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez T

rim

ethy

lpho

spha

tey

Vin

ylac

etat

ez

Rat

26A

cryl

amid

e1-

Ally

l-1-

nitr

osou

rea

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

myl

-1-n

itros

oure

aA

traz

iney

CI

dir

ectb

lue

15B

rom

ocri

ptin

em

esyl

atey

N-n

-But

yl-N

-nit

roso

urea

Cal

cium

valp

roat

eC

apta

nz 2-

Chl

oro-

11

1-tr

iuo

roet

hane

Dac

arba

zine

z D

amin

ozid

ez 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

lD

imet

hyla

min

oeth

ylni

tros

oeth

ylur

ean

itri

tesa

lt1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

ICR

F-1

59z

Isop

hosp

ham

idez

15-

Nap

htha

lene

diam

inez

Nit

robe

nzen

ez N

orle

stri

nz 4

4-T

hiod

iani

linez

Vin

ylac

etat

ez

Vag

ina

Mou

se1

AZ

Tz

Rat

2A

ZT

z N

-n-B

utyl

-N-n

itro

sour

ea( C

ontin

ued

onne

xtpa

ge)

647

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Vas

cula

rsy

stem

Ham

ster

91

2-D

imet

hylh

ydra

zine

2H

Cl

Gly

cido

lz H

exac

hlor

oben

zene

z N

-Nit

roso

-eth

yl-2

-oxo

prop

ylur

eaN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

-Nitr

oso-

oxop

ropy

lchl

oroe

thyl

urea

N-N

itro

so-o

xopr

opyl

urea

N-N

itros

o-2-

phen

ylet

hylu

rea

Vin

ylch

lori

dez

Mou

se59

A-a

-CN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-ph

enyl

hydr

azin

eA

llyl

hydr

azin

eH

Cl

Are

colin

eH

Cl

Aza

thio

prin

eB

enzi

dine

2H

Cl

2-B

iphe

nyla

min

eH

Cly

13-

But

adie

nez

Cap

tafo

lz C

arba

myl

hydr

azin

eH

Cl

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 1-

Chl

oro-

4-ni

trob

enze

ney

5-C

hlor

o-o-

tolu

idin

ey 4-

Chl

oro-

o-to

luid

ine

HC

ly p-

Chl

oroa

nilin

eH

Clz

Chl

orop

rene

z C

upfe

rron

z D

acar

bazi

nez

Dam

inoz

idez

24-

Dia

min

otol

uene

2H

Clz

12-

Dib

rom

oeth

anez

Dif

talo

ne7

12-

Dim

ethy

lben

z(a)

anth

race

ne1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylhy

draz

ine

HC

lG

lu-P

-1z

Glu

-P-2

z p-

Hyd

razi

nobe

nzoi

cac

idH

Cl

1-H

ydro

xysa

frol

ez Is

opre

neM

eA-a

-Cac

etat

ez N

-Met

hyl-

N-f

orm

ylhy

draz

ine

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

Mic

hler

rsquoske

tone

z 5-

Nitr

o-o-

tolu

idin

ey N

itro

fenz

N-N

itros

o-N

-met

hylu

reaz

Pent

achl

oroa

niso

lez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y2

34

56

-Pen

tach

loro

phen

olt

echn

ical

grad

ez n-

Pen

tylh

ydra

zine

HC

lPh

enyl

ethy

lhyd

razi

nesu

lfat

ePh

enyl

hydr

azin

eH

Cl

Ster

igm

atoc

ysti

nz Te

tra

uoro

ethy

lene

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)zo

-Tol

uidi

neH

Clz

24

6-T

rich

loro

anil

iney

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nili

neH

Clz

Ure

than

ez V

inyl

carb

amat

eV

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y 2

5-X

ylid

ine

HC

lz

Mon

key

2A

ato

xin

B1y

Ure

than

ez

Rat

32A

nilin

eH

Cly

Azo

benz

eney

Ben

zene

z C

livor

ine

Cup

ferr

onz

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neI

QH

Cl

Las

ioca

rpin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line)

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-N

itros

o-( 2

-hyd

roxy

prop

yl) -

( 2-h

ydro

xyet

hyl)

amin

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nitr

osob

is( 2

-oxo

prop

yl) a

min

eN

-Nit

roso

diet

hano

lam

ine

N-N

itro

sodi

ethy

lam

ine

N-N

itros

odim

ethy

lam

inez

N-N

itros

omet

hyl-

( 2-t

osyl

oxye

thyl

) am

ine

N-N

itros

omor

phol

ine

N-N

itro

sopy

rrol

idin

ez Pe

tasi

teni

neS

teri

gmat

ocys

tinz

Sym

phyt

ine

Tetr

auo

roet

hyle

nez

o-To

luid

ine

HC

lz T

rp-P

-2ac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

aT

here

was

nore

port

edta

rget

site

in1

spec

ies

( rat

sor

mic

e)fo

r5

chem

ical

sw

ithsu

pers

crip

tsb

utth

ech

emic

alw

asev

alua

ted

byth

epu

blis

hed

auth

oras

aca

rcin

ogen

ald

rinz

diel

drin

z N

-nit

roso

pyrr

olid

inez

23

45

6-pe

ntac

hlor

ophe

nol

( Dow

icid

eE

C-7

)ya

ndur

etha

nez

bN

asal

cavi

tyin

clud

estis

sues

ofth

eno

sen

asal

turb

inat

esp

aran

asal

sinu

ses

and

trac

hea

c Ora

lcav

ityin

clud

estis

sues

ofth

em

outh

oro

phar

ynx

phar

ynx

and

lary

nx

Ach

emic

alis

liste

dun

der

each

orga

nev

alua

ted

aspo

sitiv

ein

anex

peri

men

tin

that

spec

ies

byat

leas

t1au

thor

The

refo

rea

chem

ical

may

beli

sted

unde

rse

vera

ltar

geto

rgan

san

dev

ery

chem

ical

liste

din

the

tabl

eis

posi

tive

inat

leas

t1sp

ecie

sIn

orde

rto

com

pare

resu

ltsin

rats

and

mic

esy

mbo

lsfo

llow

chem

ical

ste

sted

inbo

thsp

ecie

sa

zin

dica

tes

that

the

chem

ical

ispo

sitiv

eat

som

esi

tein

both

spec

ies

and

ay

indi

cate

sth

atit

was

test

edin

both

butp

ositi

vein

only

1a

Nth

enu

mbe

rof

chem

ical

sw

ithat

leas

t1po

sitiv

ete

stat

that

site

inth

atsp

ecie

sB

ecau

sem

any

chem

ical

sin

duce

tum

ors

atm

ore

than

1si

tein

agi

ven

spec

ies

man

ych

emic

als

appe

arm

ore

than

once

inth

eta

ble

648

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649

species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters

RESULTS IN RATS AND MICE

For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens

TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database

Chemicals evaluated as carcinogenic in

Rats Mice

All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)

Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2

a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not

b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats

All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical

to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included

The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site

Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 9: Compendium of Chemical Carcinogens by Target Organ - Toxnet

Subc

utan

eous

Mou

se4

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

2-D

ibro

moe

than

ez N

2-c

-Glu

tam

yl-p

-hyd

razi

nobe

nzoi

cac

idG

lyci

dolz

tissu

eR

at13

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 2

4-D

iam

inot

olue

ne2

HC

lz 1

2-D

ichl

oroe

than

ez D

imet

hoxa

ne1

4-D

ioxa

nez

MeA

-a-C

acet

atez

44

-Met

hyle

ne-b

is( 2

-met

hyla

nili

ne)

o-N

itro

soto

luen

ep-

Ros

anili

neH

Clz

Tolu

ene

diis

ocya

nate

com

mer

cial

grad

e( 2

4( 8

0) -

and

26

( 20

) -)z

o-T

olui

dine

HC

lz 2

45-

Tri

met

hyla

nilin

eH

Clz

25-

Xyl

idin

eH

Clz

Test

isM

ouse

4D

ieth

ylst

ilbe

stro

lz Fi

nast

erid

eR

eser

pine

z Ta

mox

ifen

citr

atez

Rat

185-

Aza

cytid

inez

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez 1

3-B

utad

iene

z N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

Cad

miu

mch

lori

de

2-C

hlor

o-1

11-

tri

uoro

etha

ne1

1-D

ichl

oro-

1-u

oroe

than

eH

ydro

chlo

rou

oroc

arbo

n12

3M

ethy

lter

t-bu

tyle

ther

z M

ethy

lclo

fena

pate

z M

etro

nida

zole

z N

-Nit

roso

dim

ethy

lam

inez

Oxo

linic

acid

y SD

Z20

0-11

01

11

2-Te

tra

uoro

etha

ney

Tri

chlo

roet

hyle

nez

Tri

nitr

ogly

ceri

nV

inyl

chlo

ride

z

Thy

roid

glan

dH

amst

er4

Hex

achl

orob

enze

nez

Hyd

razi

nez

Met

hylt

hiou

raci

lU

reth

anez

Mou

se18

3-A

min

o-4-

etho

xyac

etan

ilide

y H

Cbl

ueno

1z

tert

-But

ylal

coho

lz C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

24

-Dia

min

oani

sole

sulf

atez

Die

thyl

stil

best

rolz

Dox

ylam

ine

succ

inat

ez E

thio

nam

idey

Eth

ylen

eth

iour

eaz

44

-Met

hyle

nedi

anil

ine

2HC

lz 1

5-N

apht

hale

nedi

amin

ez N

itrob

enze

nez

Oxa

zepa

my

44

-Oxy

dian

iline

z C

Ip

igm

entr

ed3z

Sulf

amet

hazi

ne2

37

8-T

etra

chlo

rodi

benz

o-p-

diox

inz

44

-Thi

odia

nilin

ez

Rat

33A

cryl

amid

e3-

Am

inot

riaz

olez

o-A

nisi

dine

HC

lz B

emit

radi

ne2

2-B

is( b

rom

omet

hyl)

-13

-pro

pane

diol

tec

hnic

algr

adez

Bro

mat

epo

tass

ium

z C

hlor

inat

edpa

raf

ns( C

126

0ch

lori

ne)z

Chl

orop

rene

z 2

4-D

iam

inoa

niso

lesu

lfat

ez N

N-D

ieth

ylth

iour

eay

1-E

thyl

-1-n

itro

sour

ea

Eth

ylen

eth

iour

eaz

1-E

thyl

nitr

oso-

3-( 2

-oxo

prop

yl) -

urea

Flu

vast

atin

Gly

cido

lz Io

dina

ted

glyc

erol

z Is

obut

eney

Mal

onal

dehy

des

odiu

msa

ltz

Met

him

azol

e4

4-M

ethy

lene

bis(

NN

-dim

ethy

l)be

nzen

amin

ez 4

4-M

ethy

lene

dian

iline

2H

Clz

Mir

exp

hoto

-N

itro

benz

enez

N-N

itro

sobi

s(2-

oxop

ropy

l)am

ine

44

-Oxy

dian

iline

z Pr

opyl

thio

urac

ilz p-

Ros

anil

ine

HC

lz 2

37

8-Te

trac

hlor

odib

enzo

-p-d

ioxi

nz 4

4-T

hiod

iani

linez

Thi

oura

cilz

Tri

met

hylt

hiou

reay

Vin

ylac

etat

ez Z

inc

dim

ethy

ldith

ioca

rbam

atez

Uri

nary

blad

der

Dog

23

3-D

ichl

orob

enzi

dine

44

-Met

hyle

ne-b

is( 2

-chl

oroa

nilin

e)H

amst

er3

Form

icac

id2-

[ 4-(

5-ni

tro-

2-fu

ryl)

-2-t

hiaz

olyl

] hyd

razi

dez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

acet

amid

eN

-[4-

( 5-N

itro-

2-fu

ryl)

-2-t

hiaz

olyl

] for

mam

idez

Mou

se12

2-A

cety

lam

ino

uore

nez

4-A

min

odip

heny

l2-

Am

inod

iphe

nyle

neox

ide

o-A

nisi

dine

HC

lz 4-

Chl

oro-

4-a

min

odip

heny

leth

erz

p-C

resi

dine

z 4-

Eth

ylsu

lpho

nyln

apht

hale

ne-1

-sul

fona

mid

eN

-Hyd

roxy

-2-a

cety

lam

ino

uore

nez

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez P

hena

cetin

z Te

lone

IIt

echn

ical

grad

ez U

raci

lz

Mon

key

12-

Nap

hthy

lam

inez

Rat

49A

ceta

min

ophe

nz A

llyli

soth

iocy

anat

ey 1-

Am

ino-

24-

dibr

omoa

nthr

aqui

none

z 2-

Am

ino-

4-( 5

-nitr

o-2-

fury

l)th

iazo

lez

4-A

min

o-2-

nitr

ophe

noly

11-A

min

ound

ecan

oic

acid

y o-

Ani

sidi

neH

Clz

Ari

stol

ochi

cac

ids

odiu

msa

lt( 7

7A

AI

21

AA

II)

22-

Bis

( bro

mom

ethy

l)-1

3-p

ropa

nedi

olt

echn

ical

grad

ez C

Id

ispe

rse

blue

1y N

-But

yl-N

-(4-

hydr

oxyb

utyl

) nitr

osam

ine

4-C

hlor

o-o-

phen

ylen

edia

min

ez m

-Cre

sidi

ney

p-C

resi

dine

z C

yclo

phos

pham

idez

Die

thyl

ene

glyc

olD

imet

hyla

rsin

icac

idy

Fose

tylA

lIQ

HC

lM

eA-a

-Cac

etat

ez M

elam

iney

2-M

etho

xy-3

-am

inod

iben

zofu

ran

2-N

apht

hyla

min

ez N

itril

otri

acet

icac

idz

Nitr

ilot

riac

etic

acid

tri

sodi

umsa

ltm

onoh

ydra

tey

N-[

4-( 5

-Nit

ro-2

-fur

yl) -

2-th

iazo

lyl]

form

amid

ez o-

Nitr

oani

sole

z N

-Nitr

oso-

N-m

ethy

l-N

-dod

ecyl

amin

eN

-Nitr

oso-

N-m

ethy

l-N

-tet

rade

cyla

min

eN

-Nit

roso

-N-m

ethy

ldec

ylam

ine

N-N

itros

obis

( 2-o

xopr

opyl

) am

ine

Nitr

osod

ibut

ylam

inez

N-N

itro

sodi

phen

ylam

iney

o-N

itros

otol

uene

N-O

xydi

ethy

lene

thio

carb

amyl

-N-o

xydi

ethy

lene

sulf

enam

ide

Phe

nace

tinz

Phen

azon

eo-

Phen

ylph

enat

eso

dium

y o-

Phen

ylph

enol

y P

otas

sium

bica

rbon

ate

Purp

urin

Que

rcet

iny

p-Q

uino

nedi

oxim

ey Sa

ccha

rin

sodi

umy

Sali

cyla

zosu

lfap

yrid

inez

o-To

luen

esul

fona

mid

eo-

Tolu

idin

eH

Clz

Trp

-P-2

acet

atez

Ura

cilz

Ute

rus

Ham

ster

1N

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aM

ouse

12B

rom

oeth

anez

Chl

oroe

than

ey D

acar

bazi

nez

12-

Dic

hlor

oeth

anez

Die

thyl

stil

best

rolz

Eth

ylen

eox

idez

Gly

cido

lz ( N

-6) -

( Met

hyln

itros

o)ad

enos

ine

Proc

arba

zine

HC

lz 1

23-

Tri

chlo

ropr

opan

ez T

rim

ethy

lpho

spha

tey

Vin

ylac

etat

ez

Rat

26A

cryl

amid

e1-

Ally

l-1-

nitr

osou

rea

3-A

min

o-9-

ethy

lcar

bazo

lem

ixtu

rez

1-A

myl

-1-n

itros

oure

aA

traz

iney

CI

dir

ectb

lue

15B

rom

ocri

ptin

em

esyl

atey

N-n

-But

yl-N

-nit

roso

urea

Cal

cium

valp

roat

eC

apta

nz 2-

Chl

oro-

11

1-tr

iuo

roet

hane

Dac

arba

zine

z D

amin

ozid

ez 3

3-D

imet

hoxy

benz

idin

e-4

4-d

iisoc

yana

tey

33

-Dim

etho

xybe

nzid

ine

2HC

lD

imet

hyla

min

oeth

ylni

tros

oeth

ylur

ean

itri

tesa

lt1-

Eth

ylni

tros

o-3-

( 2-h

ydro

xyet

hyl)

-ure

a1-

Eth

ylni

tros

o-3-

( 2-o

xopr

opyl

) -ur

ea

N-H

exyl

nitr

osou

rea

ICR

F-1

59z

Isop

hosp

ham

idez

15-

Nap

htha

lene

diam

inez

Nit

robe

nzen

ez N

orle

stri

nz 4

4-T

hiod

iani

linez

Vin

ylac

etat

ez

Vag

ina

Mou

se1

AZ

Tz

Rat

2A

ZT

z N

-n-B

utyl

-N-n

itro

sour

ea( C

ontin

ued

onne

xtpa

ge)

647

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Vas

cula

rsy

stem

Ham

ster

91

2-D

imet

hylh

ydra

zine

2H

Cl

Gly

cido

lz H

exac

hlor

oben

zene

z N

-Nit

roso

-eth

yl-2

-oxo

prop

ylur

eaN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

-Nitr

oso-

oxop

ropy

lchl

oroe

thyl

urea

N-N

itro

so-o

xopr

opyl

urea

N-N

itros

o-2-

phen

ylet

hylu

rea

Vin

ylch

lori

dez

Mou

se59

A-a

-CN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-ph

enyl

hydr

azin

eA

llyl

hydr

azin

eH

Cl

Are

colin

eH

Cl

Aza

thio

prin

eB

enzi

dine

2H

Cl

2-B

iphe

nyla

min

eH

Cly

13-

But

adie

nez

Cap

tafo

lz C

arba

myl

hydr

azin

eH

Cl

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 1-

Chl

oro-

4-ni

trob

enze

ney

5-C

hlor

o-o-

tolu

idin

ey 4-

Chl

oro-

o-to

luid

ine

HC

ly p-

Chl

oroa

nilin

eH

Clz

Chl

orop

rene

z C

upfe

rron

z D

acar

bazi

nez

Dam

inoz

idez

24-

Dia

min

otol

uene

2H

Clz

12-

Dib

rom

oeth

anez

Dif

talo

ne7

12-

Dim

ethy

lben

z(a)

anth

race

ne1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylhy

draz

ine

HC

lG

lu-P

-1z

Glu

-P-2

z p-

Hyd

razi

nobe

nzoi

cac

idH

Cl

1-H

ydro

xysa

frol

ez Is

opre

neM

eA-a

-Cac

etat

ez N

-Met

hyl-

N-f

orm

ylhy

draz

ine

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

Mic

hler

rsquoske

tone

z 5-

Nitr

o-o-

tolu

idin

ey N

itro

fenz

N-N

itros

o-N

-met

hylu

reaz

Pent

achl

oroa

niso

lez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y2

34

56

-Pen

tach

loro

phen

olt

echn

ical

grad

ez n-

Pen

tylh

ydra

zine

HC

lPh

enyl

ethy

lhyd

razi

nesu

lfat

ePh

enyl

hydr

azin

eH

Cl

Ster

igm

atoc

ysti

nz Te

tra

uoro

ethy

lene

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)zo

-Tol

uidi

neH

Clz

24

6-T

rich

loro

anil

iney

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nili

neH

Clz

Ure

than

ez V

inyl

carb

amat

eV

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y 2

5-X

ylid

ine

HC

lz

Mon

key

2A

ato

xin

B1y

Ure

than

ez

Rat

32A

nilin

eH

Cly

Azo

benz

eney

Ben

zene

z C

livor

ine

Cup

ferr

onz

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neI

QH

Cl

Las

ioca

rpin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line)

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-N

itros

o-( 2

-hyd

roxy

prop

yl) -

( 2-h

ydro

xyet

hyl)

amin

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nitr

osob

is( 2

-oxo

prop

yl) a

min

eN

-Nit

roso

diet

hano

lam

ine

N-N

itro

sodi

ethy

lam

ine

N-N

itros

odim

ethy

lam

inez

N-N

itros

omet

hyl-

( 2-t

osyl

oxye

thyl

) am

ine

N-N

itros

omor

phol

ine

N-N

itro

sopy

rrol

idin

ez Pe

tasi

teni

neS

teri

gmat

ocys

tinz

Sym

phyt

ine

Tetr

auo

roet

hyle

nez

o-To

luid

ine

HC

lz T

rp-P

-2ac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

aT

here

was

nore

port

edta

rget

site

in1

spec

ies

( rat

sor

mic

e)fo

r5

chem

ical

sw

ithsu

pers

crip

tsb

utth

ech

emic

alw

asev

alua

ted

byth

epu

blis

hed

auth

oras

aca

rcin

ogen

ald

rinz

diel

drin

z N

-nit

roso

pyrr

olid

inez

23

45

6-pe

ntac

hlor

ophe

nol

( Dow

icid

eE

C-7

)ya

ndur

etha

nez

bN

asal

cavi

tyin

clud

estis

sues

ofth

eno

sen

asal

turb

inat

esp

aran

asal

sinu

ses

and

trac

hea

c Ora

lcav

ityin

clud

estis

sues

ofth

em

outh

oro

phar

ynx

phar

ynx

and

lary

nx

Ach

emic

alis

liste

dun

der

each

orga

nev

alua

ted

aspo

sitiv

ein

anex

peri

men

tin

that

spec

ies

byat

leas

t1au

thor

The

refo

rea

chem

ical

may

beli

sted

unde

rse

vera

ltar

geto

rgan

san

dev

ery

chem

ical

liste

din

the

tabl

eis

posi

tive

inat

leas

t1sp

ecie

sIn

orde

rto

com

pare

resu

ltsin

rats

and

mic

esy

mbo

lsfo

llow

chem

ical

ste

sted

inbo

thsp

ecie

sa

zin

dica

tes

that

the

chem

ical

ispo

sitiv

eat

som

esi

tein

both

spec

ies

and

ay

indi

cate

sth

atit

was

test

edin

both

butp

ositi

vein

only

1a

Nth

enu

mbe

rof

chem

ical

sw

ithat

leas

t1po

sitiv

ete

stat

that

site

inth

atsp

ecie

sB

ecau

sem

any

chem

ical

sin

duce

tum

ors

atm

ore

than

1si

tein

agi

ven

spec

ies

man

ych

emic

als

appe

arm

ore

than

once

inth

eta

ble

648

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649

species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters

RESULTS IN RATS AND MICE

For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens

TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database

Chemicals evaluated as carcinogenic in

Rats Mice

All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)

Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2

a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not

b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats

All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical

to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included

The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site

Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 10: Compendium of Chemical Carcinogens by Target Organ - Toxnet

TAB

LE

1mdash

Sum

mar

yof

Car

cino

geni

cPo

tenc

yD

atab

ase

byta

rget

orga

n( C

onti

nued

)

Targ

etsi

teSp

ecie

sN

Che

mic

als

that

indu

cetu

mor

sat

each

site

Vas

cula

rsy

stem

Ham

ster

91

2-D

imet

hylh

ydra

zine

2H

Cl

Gly

cido

lz H

exac

hlor

oben

zene

z N

-Nit

roso

-eth

yl-2

-oxo

prop

ylur

eaN

-Nitr

oso-

ethy

lhyd

roxy

ethy

lure

aN

-Nitr

oso-

oxop

ropy

lchl

oroe

thyl

urea

N-N

itro

so-o

xopr

opyl

urea

N-N

itros

o-2-

phen

ylet

hylu

rea

Vin

ylch

lori

dez

Mou

se59

A-a

-CN

-Ace

tyl-

4-( h

ydro

xym

ethy

l)ph

enyl

hydr

azin

e1-

Ace

tyl-

2-ph

enyl

hydr

azin

eA

llyl

hydr

azin

eH

Cl

Are

colin

eH

Cl

Aza

thio

prin

eB

enzi

dine

2H

Cl

2-B

iphe

nyla

min

eH

Cly

13-

But

adie

nez

Cap

tafo

lz C

arba

myl

hydr

azin

eH

Cl

4-C

hlor

o-4

-am

inod

iphe

nyle

ther

z 1-

Chl

oro-

4-ni

trob

enze

ney

5-C

hlor

o-o-

tolu

idin

ey 4-

Chl

oro-

o-to

luid

ine

HC

ly p-

Chl

oroa

nilin

eH

Clz

Chl

orop

rene

z C

upfe

rron

z D

acar

bazi

nez

Dam

inoz

idez

24-

Dia

min

otol

uene

2H

Clz

12-

Dib

rom

oeth

anez

Dif

talo

ne7

12-

Dim

ethy

lben

z(a)

anth

race

ne1

1-D

imet

hylh

ydra

zine

y 1

2-D

imet

hylh

ydra

zine

2H

Cl

N-E

thyl

-N-f

orm

ylhy

draz

ine

Eth

ylhy

draz

ine

HC

lG

lu-P

-1z

Glu

-P-2

z p-

Hyd

razi

nobe

nzoi

cac

idH

Cl

1-H

ydro

xysa

frol

ez Is

opre

neM

eA-a

-Cac

etat

ez N

-Met

hyl-

N-f

orm

ylhy

draz

ine

2-M

ethy

l-1-

nitr

oant

hraq

uino

nez

Mic

hler

rsquoske

tone

z 5-

Nitr

o-o-

tolu

idin

ey N

itro

fenz

N-N

itros

o-N

-met

hylu

reaz

Pent

achl

oroa

niso

lez

23

45

6-Pe

ntac

hlor

ophe

nol(

Dow

icid

eE

C-7

)y2

34

56

-Pen

tach

loro

phen

olt

echn

ical

grad

ez n-

Pen

tylh

ydra

zine

HC

lPh

enyl

ethy

lhyd

razi

nesu

lfat

ePh

enyl

hydr

azin

eH

Cl

Ster

igm

atoc

ysti

nz Te

tra

uoro

ethy

lene

z To

luen

edi

isoc

yana

tec

omm

erci

algr

ade

( 24

( 80

) -an

d2

6( 2

0) -

)zo

-Tol

uidi

neH

Clz

24

6-T

rich

loro

anil

iney

24

5-T

rim

ethy

lani

line

HC

lz 2

46-

Tri

met

hyla

nili

neH

Clz

Ure

than

ez V

inyl

carb

amat

eV

inyl

chlo

ride

z V

inyl

uor

idez

Vin

ylid

ene

chlo

ride

y 2

5-X

ylid

ine

HC

lz

Mon

key

2A

ato

xin

B1y

Ure

than

ez

Rat

32A

nilin

eH

Cly

Azo

benz

eney

Ben

zene

z C

livor

ine

Cup

ferr

onz

12-

Dib

rom

oeth

anez

12-

Dic

hlor

oeth

anez

46-

Dim

ethy

l-2-

( 5-n

itro-

2-fu

ryl)

pyri

mid

ine

Z-E

thyl

-ON

N-a

zoxy

etha

neZ

-Eth

yl-O

NN

-azo

xym

etha

neI

QH

Cl

Las

ioca

rpin

e4

4-M

ethy

lene

-bis

( 2-c

hlor

oani

line)

N-[

5-( 5

-Nit

ro-2

-fur

yl) -

13

4-th

iadi

azol

-2-y

l] ace

tam

idez

N-N

itros

o-( 2

-hyd

roxy

prop

yl) -

( 2-h

ydro

xyet

hyl)

amin

eN

itro

so-1

23

6-t

etra

hydr

opyr

idin

eN

-Nitr

osob

is( 2

-oxo

prop

yl) a

min

eN

-Nit

roso

diet

hano

lam

ine

N-N

itro

sodi

ethy

lam

ine

N-N

itros

odim

ethy

lam

inez

N-N

itros

omet

hyl-

( 2-t

osyl

oxye

thyl

) am

ine

N-N

itros

omor

phol

ine

N-N

itro

sopy

rrol

idin

ez Pe

tasi

teni

neS

teri

gmat

ocys

tinz

Sym

phyt

ine

Tetr

auo

roet

hyle

nez

o-To

luid

ine

HC

lz T

rp-P

-2ac

etat

ez V

inyl

brom

ide

Vin

ylch

lori

dez

Vin

yl

uori

dez

aT

here

was

nore

port

edta

rget

site

in1

spec

ies

( rat

sor

mic

e)fo

r5

chem

ical

sw

ithsu

pers

crip

tsb

utth

ech

emic

alw

asev

alua

ted

byth

epu

blis

hed

auth

oras

aca

rcin

ogen

ald

rinz

diel

drin

z N

-nit

roso

pyrr

olid

inez

23

45

6-pe

ntac

hlor

ophe

nol

( Dow

icid

eE

C-7

)ya

ndur

etha

nez

bN

asal

cavi

tyin

clud

estis

sues

ofth

eno

sen

asal

turb

inat

esp

aran

asal

sinu

ses

and

trac

hea

c Ora

lcav

ityin

clud

estis

sues

ofth

em

outh

oro

phar

ynx

phar

ynx

and

lary

nx

Ach

emic

alis

liste

dun

der

each

orga

nev

alua

ted

aspo

sitiv

ein

anex

peri

men

tin

that

spec

ies

byat

leas

t1au

thor

The

refo

rea

chem

ical

may

beli

sted

unde

rse

vera

ltar

geto

rgan

san

dev

ery

chem

ical

liste

din

the

tabl

eis

posi

tive

inat

leas

t1sp

ecie

sIn

orde

rto

com

pare

resu

ltsin

rats

and

mic

esy

mbo

lsfo

llow

chem

ical

ste

sted

inbo

thsp

ecie

sa

zin

dica

tes

that

the

chem

ical

ispo

sitiv

eat

som

esi

tein

both

spec

ies

and

ay

indi

cate

sth

atit

was

test

edin

both

butp

ositi

vein

only

1a

Nth

enu

mbe

rof

chem

ical

sw

ithat

leas

t1po

sitiv

ete

stat

that

site

inth

atsp

ecie

sB

ecau

sem

any

chem

ical

sin

duce

tum

ors

atm

ore

than

1si

tein

agi

ven

spec

ies

man

ych

emic

als

appe

arm

ore

than

once

inth

eta

ble

648

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649

species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters

RESULTS IN RATS AND MICE

For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens

TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database

Chemicals evaluated as carcinogenic in

Rats Mice

All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)

Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2

a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not

b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats

All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical

to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included

The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site

Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 11: Compendium of Chemical Carcinogens by Target Organ - Toxnet

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 649

species the reader can determine that pentachloroanisole isthe only chemical that induced adrenal tumors in both rats andmice The superscripts y and z apply only to results in rats andmice for example hamsters are reported under adrenal glandfor urethane with the symbol z indicating that urethane waspositive at some site in rats and mice however the superscriptdoes not indicate anything about hamsters

RESULTS IN RATS AND MICE

For rats and mice Table 2 summarizes the proportionof carcinogens that are positive at each target organ basedon the results presented in the compendium (Table 1) InTable 2 the target sites are ordered by how frequently thesite is positive in either rats or mice A summary of the com-pendium is given under the headings ldquoAll Chemicalsrdquo forrats (N 526) and mice (N 412) Additionally for thesubset of carcinogens that have been tested in Salmonella(N 459) results in each species are reported separatelyfor mutagens and nonmutagens A chemical is classi ed asmutagenic in the Salmonella assay if it was evaluated as ei-ther ldquomutagenicrdquo or ldquoweakly mutagenicrdquo by Zeiger (17) or asldquopositiverdquo by the Gene-Tox Program (11 14) and A Auletta(personal communication April 1990) This summary tablepermits simple comparisons between species and betweenmutagens and nonmutagens

TABLE 2mdashFrequency of target organs by mutagenicity in Salmonella for 526 carcinogens in rats and 412 carcinogens in mice in the Carcinogenic Potency Database

Chemicals evaluated as carcinogenic in

Rats Mice

All chemicalsa Mutagens Nonmutagens All chemicalsa Mutagens NonmutagensTarget organ (N 526)b (N 214) (N 126) (N 412) (N 176) (N 126)

Liver 206 (39) 84 (39) 40 (32) 231 (56) 92 (52) 90 (71)Lung 55 (10) 31 (14) 3 (2) 116 (28) 54 (31) 23 (18)Mammary gland 102 (19) 60 (28) 13 (10) 24 (6) 11 (6) 8 (6)Kidney 86 (16) 31 (14) 36 (29) 26 (6) 12 (7) 10 (8)Stomach 85 (16) 45 (21) 10 (8) 63 (15) 34 (19) 14 (11)Vascular system 32 (6) 18 (8) 2 (2) 59 (14) 34 (19) 11 (9)Hematopoietic system 56 (11) 29 (14) 16 (13) 53 (13) 23 (13) 17 (13)Urinary bladder 49 (9) 25 (12) 14 (11) 12 (3) 8 (5) 1Nasal cavityturbinates 43 (8) 19 (9) 6 (5) 6 (1) 6 (3)EarZymbalrsquos gland 41 (8) 31 (14) 1 3 1 2 (2)Esophagus 36 (7) 14 (7) 1 8 (2) 5 (3) 1Skin 33 (6) 23 (11) 3 (2) 5 (1) 4 (2)Thyroid gland 33 (6) 14 (7) 12 (10) 18 (4) 9 (5) 9 (7)Oral cavity 32 (6) 18 (8) 6 (5) 3 2 (1) 1Large intestine 32 (6) 22 (10) 1 1Small intestine 29 (6) 20 (9) 2 (2) 6 (1) 4 (2) 1Uterus 26 (5) 11 (5) 6 (5) 12 (3) 8 (5) 3 (2)Peritoneal cavity 22 (4) 13 (6) 5 (4) 8 (2) 2 (1) 1Pancreas 22 (4) 8 (4) 7 (6)Central nervous system 21 (4) 14 (7) 2 (2) 3 2 (1) 1Harderian gland 19 (5) 9 (5) 7 (6)Clitoralpreputial gland 21 (4) 16 (7) 4 (3) 11 (3) 3 (2) 2 (2)Testis 18 (3) 7 (3) 4 (3) 4 2 (2)Adrenal gland 16 (3) 7 (3) 6 (5) 8 (2) 3 (2) 5 (4)Subcutaneous tissue 13 (2) 11 (5) 1 4 3 (2)Ovary 10 (2) 4 (2) 5 (4)Pituitary gland 7 (1) 2 4 (3) 8 (2) 2 (1) 3 (2)Spleen 7 (1) 4 (2) 2 (2)Bone 5 2 1Prostate 4 1 1Gall bladder 4Vagina 2 2 1 1Myocardium 2 1Mesovarium 2

a In the CPDB 722 chemicals are carcinogenic in rats andor mice but mutagenicity in Salmonella is known for only 459 of them The column ldquoAll chemicalsrdquo reports results for allcarcinogens in each species whether mutagenicity results are available or not

b Percentage of rat carcinogens or mouse carcinogens that induce tumors at the given site Many chemicals induce tumors at more than 1 site and these are counted at each relevanttarget site Therefore many chemicals are counted more than once and percentages cannot be added For example of 206 chemicals that induce liver tumors in rats 126 (61) are positivein at least one other site in rats

All Carcinogens in Rats or MiceAmong rodent carcinogens it is common for a chemical

to induce tumors at more than one site in a species and thisis re ected in Table 2 where many chemicals are counted un-der more than one site Multiple-site carcinogenesis is morecommon in rats (52 247471) than mice (45 171384)with 3 or more target sites also more common in rats (31148471 compared to 19 72384 in mice) Fewer chemi-cals are included in the multiple-site analysis than the totalsin Table 2 because multiple-site carcinogenesis cannot bemeasured for experiments that restrict histopathological ex-amination or report data for only a couple of selected tissuesResults are similar when experiments with restricted analysesare included

The liver is the most frequent target site in mice (56) andrats (39) (Table 2) The second most common sites are themouse lung (28) and the rat mammary gland (19) Amongthe 44 carcinogens in hamsters the most frequent sites arestomach and liver For the 11 carcinogens in monkeys liveris the most frequent target site

Despite the wide variety of target organs in rats and mice(Tables 1 and 2) due to (a) the frequency of multiple-sitecarcinogenesis and (b) the frequency of tumorigenesis in afew common sites like liver most chemical carcinogens inrats and mice can be identi ed by just the 8 most common

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 12: Compendium of Chemical Carcinogens by Target Organ - Toxnet

650 GOLD ET AL TOXICOLOGIC PATHOLOGY

TABLE 3mdashTarget organs in humans for 82 agents evaluated as human carcinogens by the International Agency for Research on Cancer (10 15 16)

Target site Agent mixture or industrial process

Anogenital Human papilloma virus 16Bladder Aluminum production 4-Aminobiphenyla Analgesic mixtures containing phenacetind Auramine manufactured e

Benzidinea N N -Bis(2-chloroethyl)-2-naphthylamine (chlornaphazine) Coal gasi cation Coal-tar pitchesCyclophosphamidea Magenta manufactured e 2-Naphthylaminea b Rubber industry Schistosoma hematobium (infection)Tobacco smoke

Bone Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes) as aerosols Radium-224and its decay products Radium-226 and its decay products Radium-228 and its decay products

Brain Vinyl chloride a

Breast Diethylstilbestrola Estrogens nonsteroidala e Estrogens postmenopausa l therapyd e X-rays and c -raysCervix Human papilloma virus 16 Human papilloma virus 18Cervixvagina Diethylstilbestrola Estrogens nonsteroidala e

Endometrium Estrogens steroidalae Estrogens postmenopausa l therapyd e Oral contraceptives sequential Tamoxifena

Esophagus Alcoholic beveragesd Tobacco smokeGastrointestinal tract AsbestosHematopoietic system

Leukemia Benzenea Boot and shoe manufacture and repair 14-Butanediol dimethanesulphonat e (Myleran)c Chlorambucila 1-(2-(Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) Cyclophosphamidea Etoposide in combinationwith cisplatin and bleomycin Melphalana MOPP and other combined chemotherapy including alkylating agentsPhosphorus-32 as phosphate Rubber industry Thio-tepaa Thorium-232 and its decay products administered intravenously as

a colloidal dispersion of thorium-232 dioxide Treosulfan X-rays and c -raysLymphoma Azathioprinea Cyclosporinc Epstein-Barr virus Human immunode ciency virus type 1 (HIV-1) Human T-cell

lymphotropic virus type I (HTLV-I) Vinyl chloridea

Hodgkinrsquos disease Epstein-Barr virusKaposirsquos sarcoma Human immunode ciency virus type 1 (HIV-1)Kidney Coke production

Renal pelvis Analgesic mixtures containing phenacetin (renal pelvisureter)d Tobacco smokeLiver A atoxinsa b Alcoholic beveragesd Hepatitis B virus (chronic infection) Hepatitis C virus (chronic infection)

Opisthorchis viverrini (infection) Oral contraceptives combineda e Plutonium-239 and its decay products (may containplutonium-240 and other isotopes) as aerosols Vinyl chloridea

Cholangiocarcinoma Opisthorchis viverrini (infection)Hepatobiliary system Azathioprinea

Lung Aluminum production Arsenic and arsenic compoundsa Asbestos Beryllium and beryllium compoundscBis(chloromethyl)ethera and technical choromethyl methyl ethera Cadmium and cadmium compoundsa Chromium (VI) compounds a Coal gasi cation Coal-tar pitches Coal-tars Coke production Mustard gas (sulphur mustard)

Hematite mining (underground) with exposure to radon Iron and steel founding Nickel compoundsc Painter (occupationa l exposure) Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes)as aerosols Radon-222 and its decay products Silica crystalline in the form of quartz or cristobalite from occupationa l sourcesSoots Strong inorganic acid mists containing sulfuric acid (occupationa l exposure) Talc containing asbestiform bersThorium-232 and its decay products administered intravenously as a colloidal dispersion of thorium-232 dioxide Tobacco smokeVinyl chloridea

Mesenchymal tumors Azathioprinea

Nasal sinus Boot and shoe manufacture and repair Furniture and cabinet making Isopropanol manufacture (strong acid process)Nickel compoundsc Wood dust

Nasopharynx Epstein-Barr virus Salted sh Chinese-styleParanasal sinus Wood dust

Oral cavity Alcoholic beveragesd Betel-quid with tobacco Tobacco products smokeless (chewing tobacco oral snuff ) Tobacco smokeLarynx Alcoholic beveragesd Asbestos Mustard gas (sulphur mustard) Strong inorganic acid mists containing sulfuric acid

(occupationa l exposure) Tobacco smokePharynx Alcoholic beveragesd Mustard gas (sulphur mustard) Tobacco smoke

Pancreas Tobacco smokePeritoneum Asbestos ErionitePleura Asbestos ErioniteSkin Arsenic and arsenic compoundsa Azathioprinea Coal gasi cation Coal-tar pitches Coal-tars Coke production

8-Methoxypsoralen (methoxsalen)a plus UV radiation Mineral oils untreated and mildly treated Shale-oils Solarradiation Soots

Melanoma Solar radiationStomach Helicobacter pylori (infection)Testis Diethylstilbestrola Estrogens nonsteroidala e

Thyroid Radioiodines short-lived isotopes including iodine-131 from atomic reactor accidents and nuclear weapons detonation(exposure during childhood) X-rays and c -rays

IARC has evaluated an additional 5 agents as having an overall evaluation ldquocarcinogenic to humansrdquo but all 5 lack an IARC evaluation of ldquosuf cient evidencerdquo of carcinogenicity tohumans a -particle-emitting radionuclides internally deposited b -particle-emitting radionuclides internally deposited ethylene oxide neutron radiation and TCDD

IARC has evaluated the evidence of carcinogenicity in animals as ldquosuf cientrdquo for these 40 human carcinogens aTissues are reported in Table 1 for rodent experiments in the CPDBbTissues reported in Table 1 for monkey experiments in the CPDBcExperiments are reported in the CPDB but none are positived For 5 chemicals there are positive tests with target sites in the CPDB however for the agent or exposure circumstance evaluated by IARC as ldquocarcinogenic to humansrdquo there are no

tests in the CPDB auramine-O estradiol ethyl alcohol phenacetin and rosaniline (Magenta I)eFor 6 human carcinogens IARC considers the evidence of carcinogenicity in experimental animals as ldquosuf cientrdquo for some chemical constituent but the group or exposure circumstance

is not evaluated as ldquosuf cientrdquo in animals auramine manufacture estrogens steroidal and nonsteroidal estrogens postmenopausal therapy magenta manufacture and oral contraceptives combined

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 13: Compendium of Chemical Carcinogens by Target Organ - Toxnet

Vol 29 No 6 2001 TARGET ORGANS OF CARCINOGENESIS 651

sites liver lung mammary gland stomach vascular systemkidney hematopoietic system and urinary bladder (7) Over-all 92 (354384) of mouse carcinogens and 82 (388471)of rat carcinogens are positive in at least one of these 8 sites

Mutagenicity and Target SiteMutagens compared to nonmutagens are (a) more likely to

be carcinogenic (b) more likely to induce tumors at multipletarget sites and (c) more likely to be carcinogenic in 2 species(4 5 8)

Since tissue distribution and pharmacokinetics would notbe expected to differ systematically between mutagens andnonmutagens one would not expect systematic differencesin the particular organs in which tumors are induced (8)Results in Table 2 do not support the idea that mutagens andnonmutagens induce tumors in different target organs Liveris the most common site for both mutagens and nonmutagensmost organs are target sites for both mutagens and nonmuta-gens and both mutagens and nonmutagens induce tumors ina wide variety of sites Moreover the same sites tend to be themost common sites for both at least 81 of either mutagensor nonmutagens are positive in each species in at least one ofthe 8 most frequent target sites We earlier compared resultsfor mutagens and nonmutagens in speci c tissues (18)

Target Organs of Human CarcinogensTo complement the compendium of target organs in car-

cinogenesis bioassays (Table 1) Table 3 reports the targetorgans of carcinogenicity in humans for 82 agents that theInternational Agency for Research in Cancer (IARC) evalu-ates as human carcinogens at a particular target site (10 1516) httpwwwiarcfr In addition to individual chemicalssuch as those reported in Table 1 for bioassays the agents thatIARC evaluates as human carcinogens include industrial pro-cesses therapeutic combinations infectious agents ionizingradiation and mixtures such as tobacco smoke

In Table 3 footnotes indicate which chemicals are in-cluded in the CPDB among the 82 IARC human carcino-gens with human target sites The reader can comparepositivity and target sites in humans rodents and mon-keys for human carcinogens by searching for a chem-ical name in our table ldquoResults by Chemicalrdquo on theWeb (httppotencyberkeleyeduchemicalsummaryhtml) orin our plot of the CPDB (httppotencyberkeleyedudatabasehtml)

Among the 82 human carcinogens with target sites IARCconsiders 52 to have been adequately tested in experimen-tal animals Agents that have not been tested adequately aremostly exposure circumstances like the workplace or infec-tious agents Of the 52 that have been tested in animals IARCevaluates 12 as having ldquolimited evidencerdquo in animals and 40as ldquosuf cient evidencerdquo (The 40 include 6 agents for whicha chemical constituent has ldquosuf cient evidencerdquo even thoughthe group or exposure circumstance that is a human carcino-gen does not eg auramine-O for auramine manufacture)The 40 agents with ldquosuf cient evidencerdquo in animals are indi-cated in Table 3 by a ldquo rdquo Thus evidence of carcinogenicityis ldquosuf cientrdquo in experimental animals for only 4082 (49)of human carcinogens

Ultimately for purposes of investigating interspecies ex-trapolation or the practice of risk assessment to humans from

bioassay data one wants to know whether the large num-ber (many hundreds) of chemicals that have been shown tobe carcinogenic in experimental animals would also be car-cinogenic in humans This question cannot be answered byreversing the question that is by asking whether the smallnumber of chemicals that are carcinogenic to humans are alsocarcinogenic in rodent bioassays The reason for this is thateven if most human carcinogens were carcinogenic to exper-imental animals the converse does not necessarily follow ascan be demonstrated by a simple probabilistic argument (1)

ACKNOWLEDGMENTS

We thank the hundreds of scientists who have assisted usin developing the CPDB over the past 20 years by provid-ing us with additional information on their experiments Wealso thank Bruce N Ames and Jerry M Rice for their helpfuladviceThis work was supported by the National Institute ofEnvironmental Health Sciences through the University ofCalifornia Berkeley (UCB) Center Grant ESO1896 andthrough the EO Lawrence Berkeley National Laboratory(LBNL) by an Interagency Agreement (YIES101901)with the US Department of Energy (DOE) DE-AC-03-76SFO0098 Work was also supported by DOE DE-AC-03-76SFO0098 and by the Deanrsquos Of ce of the Collegeof Letters and Science at UCB for research in diseaseprevention

REFERENCES

1 Freedman DA Zeisel H (1988) From mouse to man the quantitative as-sessment of cancer risks Stat Sci 3 3ndash56

2 GoldLS ManleyNB Slone TH Rohrbach L (1999) Supplement to the Car-cinogenic PotencyDatabase (CPDB) Results of animal bioassays publishedin the general literature in 1993 to 1994 and by the National ToxicologyProgram in 1995 to 1996 Environ Health Perspect 107(Suppl 4) 527ndash600

3 Gold LS Manley NB Slone TH Rohrbach L (in preparation) Supplementto the Carcinogenic Potency Database (CPDB) Results of animal bioassayspublished in the general literature in 1995 to 1996 and by the NationalToxicology Program in 1997 to 1998

4 Gold LS Slone TH Ames BN (1997) Overview of analyses of the car-cinogenic potency database In Handbook of Carcinogenic Potency andGenotoxicity Databases (Gold LS Zeiger E eds) CRC Press Boca RatonFL pp 661ndash685

5 Gold LS Slone TH Ames BN (1998) What do animal cancer tests tell usabout human cancer risk Overview of analyses of the carcinogenic potencydatabase Drug Metab Rev 30 359ndash404

6 Gold LS Slone TH Ames BN Manley NB Gar nkel GB Rohrbach L(1997) Carcinogenic Potency Database In Handbook of Carcinogenic Po-tency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 1ndash605

7 Gold LS Slone TH Manley NB Bernstein L (1991) Target organs inchronic bioassays of 533 chemical carcinogens Environ Health Perspect93 233ndash246

8 Gold LS Slone TH Stern BR Bernstein L (1993) Comparison of target or-gans of carcinogenicity for mutagenic and non-mutagenic chemicals MutatRes 286 75ndash100

9 Haseman JK Huff JE Zeiger E McConnell EE (1987) Comparative resultsof 327 chemical carcinogenicity studies Environ Health Perspect 74 229ndash

23510 International Agency for Research on Cancer (1971ndash2001) IARC Mono-

graphs on the Evaluation of Carcinogenic Risk of Chemicals to Humansvol 1ndash78 Suppl 7 Lyon France IARC

11 Kier LE Brusick DJ Auletta AE Von Halle ES Brown MM SimmonVF Dunkel V McCann J Mortelmans K Prival M Rao TK Ray V (1986)The Salmonella typhimuriummammalian microsomal assay a report of the

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729

Page 14: Compendium of Chemical Carcinogens by Target Organ - Toxnet

652 GOLD ET AL TOXICOLOGIC PATHOLOGY

US Environmental Protection Agency Gene-Tox Program Mutat Res 16869ndash240

12 National Cancer Institute (1976ndash1980) Reports of NCI Bioassays of Chem-ical for Possible Carcinogenicit y Bethesda MD National Cancer Institute

13 National Toxicology Program (1980ndash1998) Reports of NTP Toxicology andCarcinogenesi s Studies of Chemcials in F344N Rats and B6C3F1 MiceResearch Triangle Park NC National Toxicology Program

14 US National Library of Medicine (2001) Gene-Tox Databasehttptoxnetnlmnihgovcgi-binsishtmlgenGENETOX

15 Vainio H Wilbourn J (1993) Cancer etiology agents causally associatedwith human cancer Pharmacol Toxicol 72 (Suppl 1) 4ndash11

16 Vainio H Wilbourn JD Sasco AJ Partensky C Gaudin N Hesel-tine E Eragne I (1995) Identi cation des facteurs cancerogenes pourlrsquohomme dans les Monographies du CIRC Bull Cancer 82 339ndash

34817 Zeiger E (1997) Genotoxicity database In Handbook of Carcinogeni c

Potency and Genotoxicity Databases (Gold LS Zeiger E eds) CRC PressBoca Raton FL pp 687ndash729


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