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i
PESTICIDES
A Posi tion Paper of the
AMERICAN COUNCIL
ON SCIENCE AND HE ALTH
Professor Allan S. Felsot
Washington State University
&HealthM y t h s v s . R e a l i t i e s
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Pest ic ides & Heal th: Myths vs . Real i t ies
John Berlau
Compeiive Enerprise Insiue
Christine Bruhn, Ph.D.Universiy o Caliornia, Davis
Janice E. Chambers, Ph.D., D.A.B..,A..S.Mississippi Sae Universiy
Jay Lehr, Ph.D.Te Hearland Insiue
Bob Krieger, Ph.D.Universiy o Caliornia, iverside
Manfred Kroger, Ph.D.Te Pennsylvania Sae Universiy
Angela Logomasini, Ph.D.Compeiive Enerprise Insiue
Alan McHughen, D.Phil.Universiy o Caliornia, iverside
AcknowledgementsTe American Council on Science and Healh (ACSH) appreciaes
he conribuions o he reviewers named below:
ACSH acceps unresriced grans on he condiion ha i is solely responsible orhe conduc o is research and he disseminaion o is work o he public. Teorganizaion does no perorm proprieary research, nor does i accep supporrom individual corporaions or specific research projecs. All conribuions o
ACSHa publicly unded organizaion under Secion 501(c)(3) o he Inernalevenue Codeare ax deducible.
Individual copies o his repor are available a a cos o $5.00. educed prices or10 or more copies are available upon reques.
Published by he American Council on Science and Healh, Inc.May 2011. Tisbook may no be reproduced in whole or in par, by mimeograph or any ohermeans, wihou permission o ACSH.
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Table of ContentsAcknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .iii
Table of Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iv
Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
A Rationale for Confronting Myths
about Pesticide Technology . . . . . . . . . . . . . . . . . . . . . . . . . 3
Pesticides with Benefits for All:
An Agricultural Perspective . . . . . . . . . . . . . . . . . . . . . . . . . 5
Agricultural Reality: The Economic Perspective . . . . . . . . . . . . . . . . . . . 5
Agricultural Reality: Practical & Environmental Advantages
of Crop Protection Chemicals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Pesticides with Benefits for All:
A Public Health Perspective . . . . . . . . . . . . . . . . . . . . . . . . 11
The Public Health Reality: Historical and Modern . . . . . . . . . . . . . . 11
Synthetic Chemistry for Crop Protection: Humans Imitate
Plants and Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Technological Reality: Weve Always Copied
the Good Ideas of Plants and Bacteria . . . . . . . . . . . . . . . . . . . . . . . 14
Youve Come a Long Way, Baby . . . . . . . . . . . . . . . . . . . . . . 16
The Reality of Modern Pesticide Technology:
Dynamics & Evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Its Still About the Dose(and Timing) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
The Reality of A Modern Biochemical Perspective
on Toxicity, Hazard, and Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Thresholds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
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Endocrine Disruption: Is It Just Hormonal? . . . . . . . . . . . . 25
The Reality: Confusion Between a Changing Paradigm and a Shift
in Focus, Away from Cancer, to a Different Physiological System . . 25
Vetting and Regulating Pesticides . . . . . . . . . . . . . . . . . . . 28
The Reality of Pesticide Regulation in the U.S.: An Example
of Moving the Precautionary Principle from Idealistic Philosophyto Real World Implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
The Reality of Pesticide Regulation: Truckloads of Data on Every
Conceivable Effect from Studies with Overlapping and Redundant
Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Whose Data Are They? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
How EPA Determines Safety Under the Mandates of the Law . . . . . 33
Some Case Studies: Reports
of Hazards Do Not Reflect Risks . . . . . . . . . . . . . . . . . . . . 35
Atrazine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35Chlorpyrifos . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Pyrethroid Insecticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Glyphosate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
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Executive Summary
Will we aver a crisis o ood supply shorage? Tis quesion coninues oloom large alhough populaion growh rae has empered considerably,compared o projecions 30 years ago. Bu several years ago, as ood prices
seemed o be on he verge o skyrockeing, owing o
rapid increases in grain prices, we arguably go a aseo he uure. When you consider uncerainy abou cli-
mae variabiliy and land use changes as well, we seem
always on a precipice o doing wih less raher han
more. Forunaely, agriculural echnology has hus ar
kep pace wih a growing populaion. A crucial com-
ponen o his oolbox has hisorically been a dynamic
chemical echnology, led by he availabiliy o synheic
erilizers and innovaions in chemical pes conrol.
Tis repor analyzes he myhs surrounding pesicide
science and correcs each wih a realisic perspecive o
he echnology: how i is possible o kill pess wihou
harming oher organisms, how he science is regulaed
wih a precauionary perspecive, and, finally, wih an
analysis o claims made abou hazards and he probabil-
iy ha hese pose credible risks o healh. Tis repor
makes he case or he benefis o pesicides, ranging
rom he proecion o crop yields o he proecion o
public healh. Indeed, he benefis are abundan enough
ha one can simply sae ha he availabiliy o pesi-cides has significanly improved human healh.
Conroversy surrounding pesicide use a firs
glance would seem o dae back o he 1962 publicaion
o achel Carsons Silen Spring. However, his superfi-
cial analysis ignores he long hisory o pesicide conrol
saues such as he Federal Food, Drug, and Cosmeic
Ac (FFDCA 1938) and he Federal Insecicide, Fungi-
cide, odenicide Ac (FIFR 1947). One migh argue
abou he effeciveness o hese laws, bu hey have beenamended many imes, beore and afer Silen Spring,
o address heir weaknesses. Indeed, perhaps he mos
ar-reaching modificaion was he Food Qualiy Proec-
ion Ac o 1996 which, or he firs ime, oriened he
main law, FIFR, o consider risk o consumer healh
as he only basis or re-regisering older chemicals and
regisering new producs. Veneraion o Silen Springby
advocacy groups has overlooked he reams o daa al-
ready in he public secor ha Carson had been reading
o inorm her lierary endeavor.
And so, curren pesicide laws have evolved and
are arguably he mos precauionary o all congressio-
nal mandaes involving echnology. Indeed, we asser
ha modern pesicide laws epiomize in acion an oh-
erwise vacuous precauionary principle ha eschews
risk assessmen as a basis or risk managemen. isk
assessmen righully recognizes he oo ofen ignored
principles ha all chemicals (wheher plan-derived
or cooked up by humans) are subjec o he samephysical laws o hermodynamics and he principles
o kineics. Such recogniion explains how we humans
can ea a myriad mixure o plan chemicals, many
o which are recognized as oxins hemselves, arising
rom an evoluion o plan meabolism ha aids heir
survival agains voracious predaors and he vagaries
o weaher.
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2
Execut ive Summary
disposiion wihin he body, his repor specifically
examines he claims abou our ypes o conempo-
rary pesicidesarazine, chlorpyrios, pyrehroids,
and glyphosae. In each case sudy, he published
scholarly lieraure is used o show ha he percep-ion o adverse effecs has arisen as a resul o misak-
ingeiher hrough ignorance or ideologylabora-
ory sudies o oxicological mechanisms or analysis
o risk based on consideraion o how he chemicals
are acually used.
One imporan poin o consider in any analysis
o pesicide echnology is he evoluion o a dynamic
sysem o managemen. Ta is, any repors o adverse
effecs are deal wih by developmen and implemen-
aion o new esing requiremens or by changes in
permissible uses o a produc. Te sysem provides
eedback o boh regulaory agencies and manuacur-
ers hemselves. Te later have hisorically responded
by a ocus on discovery o new producs ha mee he
goals o a saer chemical echnology. Unorunaely,
public atiudesed by atenion-seeking media
scare sories seem ocused on he pas and ail o see
a comparaively rapid change in chemical echnology
and how i has been deployed. Similarly, public aten-ion is drawn o misinerpreaions and hal-analysis o
sories o hazards. However, scruiny o he published
lieraure has ailed o find evidence o a credible prob-
abiliy o adverse human healh effecs derived rom
he use o modern pesicides as occurs in he real world,
no in he laboraory-generaed environmen. Despie
he headlines o hazard, modern chemical echnology
provides hope or coninued improvemen o human
healh, wheher helping o make vegeables and ruis
o high qualiy more abundan and cheaper, or o pre-
serve (or indeed, enhance) he healh o individuals
and sociey a large.
In his background o survival, he principle o
reasonable cerainy o no harm guides decisions
abou releasing man-made pesicides o help in he
batle o proec crop yields and ood qualiy. Eco-
nomic analyses prove how ood supply would becomeprecarious wihou he use o chemical echnology.
Epidemiological analyses prove how eliminaing an
effecive surace-sprayed insecicide like DD has os-
ered large oubreaks o malaria, he mosquio-borne
scourge o 300 million humans a year. Ye despie
he proven benefis o pesicides, years o research
have shown ha hese valuable ools canno be used
wihou proper managemen, and ha, moreover,
hey should exhibi seleciviy o pess over nonarge
organisms so ha hey become complemenary o
naural biological conrol processes exising wihin all
agriculural ecosysems.
Indusry has responded o he goals and needs
o a compaible pesicide echnology wih develop-
men o ever more selecively oxic chemicals ha
are used a comparaively low raes compared o he
chemicals hey are replacing in he markeplace. Te
recen generaions o EPA-designaed reduced-risk
pesicides are in many cases ens o hundreds o imesless oxic o fish, birds, and nonarge predaors and
parasioids han chemicals ha were inroduced o
armers beween he 1950s and 1970s. However, he
biochemical heory o ligand-recepor and enzyme-
subsrae kineics, in combinaion wih consideraions
o pharmacokineics, is applied herein o show ha
some o he older chemicals acually presen litle risk
o adverse effecs in associaion wih realisic environ-
menal raes o use.
Following explicaions o oxicological mecha-
nisms o seleciviy and he imporance o consider-
ing pharmacokineic acors influencing pesicide
Despite the headlines of hazard, modern chemical technology
provides hope for continued improvement of human health.
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3
ing risk. While consumers are reacing by expressing
heir eelings abou a generic echnology, he scienific
exper is mos likely ocusing on he idiosyncrasies o
an individual compound. Neverheless, general prin-
ciples o biochemisry and physiology are imporan
or assessing pesicide echnology. Applicaion o
hese principles is crucial o properly regulaing as well
as using he echnology. Furhermore, he benefis o
he echnology mus be considered in ligh o he pos-sible and likely adverse consequences o notusing i.
Te lieraure on he percepion and communica-
ion o risk suggess ha perhaps consumers are no
he real audience in need o inormaion abou he
inricacies o pesicide echnology. For example, 84%
o surveyed residens in Washingon Sae did no
hink pesicide use and conrol was an environmenal
problem (LaFlamme and VanDerslice 2004). I seems
ha inormaion may be beter direced o legislaive
members and heir saff (Cohen 1997). When hesecohors were surveyed, he mos desired inormaion
was explanaions o how risk assessmens are con-
duced, wih applicaion o paricular chemicals as an
example. I legislaors and heir saffs are recepive o a
beter undersanding o chemical echnology hrough
risk assessmen, hen dispelling misconcepions abou
pesicides as a precursor o raional risk manage-
A Rationale for Confronting Mythsabout Pesticide Technology
O
ver he las decade, ood preerence surveys as well as sales saisics show anincreasing percenage o consumer preerence or buying organic, raw, and
processed ood producs (Saba and Messina 2003; Hughner e al. 2007).Alhough he absolue numbers o individuals pur-
chasing hese ood iems compared o convenional
iems is sill quie small (Hughner e al. 2007), he daa
seem o validae he percepion ha consumers gener-
ally have a negaive opinion o pesicide use (Chipman
e al. 1995; Makaouni 2002; Magnusson e al. 2003;
Yiridoe e al. 2005). Tis negaive opinion is relaed o
several concerns, ranging rom worry abou he healh
effecs o pesicide residue exposure o a misrus oindusries synhesizing and markeing pesicides
(Chipman e al. 1995; Slovic 1999). Various surveys
also sugges ha consumers do no perceive any bene-
fis rom he use o pesicide echnology (Hansen e al.
2003). Consumers may undersand he need o man-
age crop and livesock pess, bu hey may also hink
ha pesicides are no necessary o achieve his goal,
or, alernaively, ha hey are overused in agriculure
(Chipman e al. 1995). isk percepion surveys gen-
erally agree ha consumers view pesicides as a highhazard echnology ha is unconrollable, unknowable,
and o litle benefi o hemselves (Chipman e al.
1995; Slovic 1987).
Given ha pesicide echnology encompasses
a vas array o individual chemicals and ormulaed
producs, changing consumer percepions seems o
presen an insurmounable obsacle in communica-
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4
A Rat iona le for Confro nt ing Myths about Pest ic ide Te chnology
icide echnology, his repor will firs sae miscon-
cepions or myhs abou pesicides ha can be gleaned
rom a combinaion o risk percepion lieraure, as
well as examining pesicide sories in he media (Fel-
so 2010). Afer saing a myh, he realiy based onbiochemical principles will be explained. Similarly,
misconcepions relaed o he real benefis o pesicide
use will be answered wih examples o how pesicides
acually conribue o proecion o human healh and
a general improvemen in wellbeing. Finally, o illus-
rae how misundersandings o he naure o oxicol-
ogy and epidemiology sudies conribue o a skewed
conflaion o hazard and risk, he repor will review
some commonly used biodegradable pesicides and
atemp o alleviae issues o specific concern. By dis-
cussing misconcepions and realiies abou pesicide
echnology, and highlighing paricular pesicides,
his repor can provide risk communicaors wihin he
business communiy and governmen wih a sronger
echnical basis or discussing pesicide issues.
One cavea needs emphasis up ron. Argumens
promoing global benefis rom pesicide echnologies
as heyve evolved over he pas 40 years are no argu-
mens agains ensuring ha hese compounds havelitle risk as hey are used. aher, our regulaory sys-
em or pesicides has acually been quie precauion-
ary. Ironically, as calls or adopion o a precauionary
principle in place o a risk assessmen process have
begun o permeae governmenal regulaory aciviy,
pesicides are arguably he one echnology where so-
called enes o his principle are acively praciced.
Tus, anoher objecive o his repor is o clariy
muliple aspecs o pesicide echnology ha mus
be known i we wish o move pas he myh ha we
have no properly considered hazards in he mids o
overwhelming benefis.
men may no be an insurmounable ask. Afer all,
legislaures mandae regulaion o he echnology.
egulaors hemselves, hereore, mus undersand
undamenal biochemical principles, as hey regulae
many kinds o chemicals.Ye simply educaing regulaors may no be an e-
ecive way o dispel misconcepions. Comparisons o
lay and exper opinion abou chemical hazards in gen-
eral revealed unpredicable disagreemens abou he
hazard and risk o chemical echnology among expers
(or example, regulaors and academic or indusry re-
searchers engaged in some aspec o oxicology) ha
were no oo differen rom hose expeced beween
consumers and expers (raus e al. 1992; Merz e
al. 1998). I here is as wide a divergence o opinion
among expers hemselves as ha which occurs be-
ween expers and consumers, one canno expec o
be very successul a risk communicaion unless some
o hese percepions are addressed direcly. Perhaps
wihin he echnical communiy isel insufficien a-
enion has been paid o common wisdom in order
o deermine operaional misconcepions abou pesi-
cide echnology in general.
Tis repor is a response o a need expressed oracual inormaion among legislaive auhoriies, bu
i also addresses expers hemselves by considering
enuous he assumpion o agreemen abou he risks
o chemical echnologies. Our analysis subsiues ac-
ual inormaion (some undamenal principles o ox-
icology based on biochemical conceps, an overview
o properies o modern reduced risk pesicides, and
a delineaion o pesicide benefis o human wellbe-
ing) or misconcepions specifically abou pesicide
echnology.
o communicae he undamenal principles o
oxicology necessary or appropriaely regulaing pes-
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5
Pesicide and erilizer use has been recorded since
ancien imes, suggesing ha ecosysem managemen
is no a recen culural atribue. In he conex o mod-
ern agriculure, he objecives o pesicide use are o
increase producion efficiency and yields; reduce he
cos o ood and, especially, o increase he availabiliy
o grains, ruis, and vegeables; improve ood qualiyand losses during ranspor and sorage; improve soil
conservaion; and ensure a sable and predicable ood
supply (NRC 2000).
Pesicide use is widespread on arms, bu more
imporanly, differen classes o pesicides are differen-
ially used (NRC 2000; Padgit e al. 2000), suggesing
ha growers make decisions based on need raher
han solely on prophylaxis. For example, in he U.S.
during 2002 approximaely 303 million acres o crops
were harvesed, and 95% were reaed wih some ype
o pesicide. However, 64% o he acreage was reaed
o conrol weeds (i.e., herbicide use), 22% o conrol
insecs (insecicide use), 6% o conrol diseases and
nemaodes (ungicide and nemaicide use). Anoher
4% o he crop acreage was reaed wih a plan growh
regulaor or rui hinning, growh conrol, or deolia-
ion (Felso and acke 2007).
Pesticides with Benets for All:An Agricultural Perspective
Myth: Farmers use pesicides or heir own economic gain wihou regard or needor a social responsibiliy o proec he environmen. Pesicides are no needed or
arming, as has been proven by he increasing adopion o organic arming.
Agricultural Reality: The Economic Perspective
Te proporional use o differen kinds o pesicides
(i.e., herbicides, insecicides, ungicides, ec.) shows ha
armers do no monolihically use he chemicals on ev-
ery acre. aher, he daa show ha use is ied o specific
need. Furhermore, he inensiy o specific pesicide
classes also varies significanly by crop. Grains end o
be disproporionaely reaed wih herbicides, bu ruiand vegeables mosly receive insecicide and ungicide
applicaions (able I). Farmers use he echnology
ha conrols he pes a hand bu, imporanly, use
is driven by need as influenced by weaher condiions,
anicipaed and acual pes inesaions, and he balanc-
ing o coss and reurns.
Te benefis o crop proecion chemicals or im-
proving and proecing crop produciviy is difficul
o separae rom he effecs o hybrid seed echnol-
ogy and oher plan breeding advances. Neverheless,
an examinaion o crop yields relaive o land under
producion shows ha boh ypes o echnologies
have had major conribuions. For example, he grea-
es proporion o U.S. armland is devoed o corn
producion. A hisorical examinaion o area o land,
yields, and he inroducion o differen echnologies
over ime suggess ha insec conrol (mainly o he
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6
Pest ic ides wi th Benef i ts for Al l : An Agricul tural Perspect ive
and umigans, in crop producion efficiency is sug-
gesed by poao producion saisics. In 1900, nearly
3 million acres o poaoes were harvesed, yielding an
average o 52 cw/acre (USDA2005). In 1950, aver-
age yields were 153 cw/acre. In crop year 2004, 1.2million acres o harvesed poaoes yielded an average
752 cw/acre. Surely, advances in plan breeding play
an imporan role in producion increases, bu by he
1950s, umigans or conrol o nemaodes became
widely available nearly coincidenally wih he
corn rooworm complex) has grealy enhanced he
effeciveness o hybrid seed echnology (Figure 1).
Furhermore, he inroducion o modern synheic
herbicides aciliaed widespread adopion o conser-
vaion illage in he Corn Bel, which in urn grealy re-duced he major cause o environmenal degradaion
in Norh Americasoil erosion and sedimenaion in
rivers (Pimenel e al. 1995).
Perhaps an even more compelling case or he role
o crop proecion chemicals, especially ungicides
Crop Herbicide Insecticide Fungicide
Corn 95 29
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7
Pest ic ides & Heal th: Myths vs . Real i t ies
o decreased pesicide use or no use seem large, he
acual decrease in yields (and consequen effecs on
consumer prices) would depend on he availabiliy o
oher alernaive crop proecion echnologies or prac-
ices (NC 2000). For example, field crops like corncan be grown wih minimal herbicide use i illage is
used more requenly. Addiionally, hand weeding, as
is ofen praciced in cerified organic crop producion,
along wih illage, can subsiue or herbicide use.
However, aggregae analysis o grain, vegeable, and
rui crop managemen, assuming only hand weeding
and illage wihou herbicide use, showed an average
yield reducion o 20 percen (Gianessi and eigner
2007). Furhermore, subsiuion o increased illage
or weed conrol would couner he benefis o re-
duced illage or soil conservaion.
Vegeable and rui producion would likely be
he mos adversely affeced by wholesale loss o use o
insecicides and ungicides, owing o heir dispropor-
ional problems wih insec pess and plan pahogens.
Loss o pesicide availabiliy would also adversely a-
ec consumer prices, and poenially mean a loss o
domesic sources o supply as producion is relocaed
o oher regions (Zilberman e al. 1991).Is imporan o realize ha he economic reurn-
cos raio or pesicide use is generally avorable. Te
raio depends on he specific crop because he annual
commodiy price mus be acored in, as well as he
sie-specific yield and expenses due o chemical pur-
chases. Neverheless, older esimaes or reurn ranged
rom $4-$29 or every $1 spen (Mecal and Luckman
1975), and more recen esimaes sugges a $3-$6 rae
o reurn per $1 spen (Zilberman e al. 1991; Pimenel
e al. 1992). Significan or he grower is he compara-
ively low incremenal cos o pesicide use relaive o
all producion expenses. Te mos recen esimae
(crop year 2002) is ha purchase o pesicides repre-
sens 4.4% o oal expenses, compared o he 12.7%
o expenses or hired and conrac arm labor (USDA
2004). Pesicides hemselves help lower coss by sub-
siuing or labor. For example, rui hinning required
widespread adopion o mineralized erilizers. Bu he
producion rends srongly sugges an environmenal
benefi because presenly seven imes more poaoes
are produced per acre han were produced in 1900. I
one hus exrapolaes or oher crops ha yields haveincreased owing o adopion o modern echnolo-
gies like improved breeding using bioechnology and
chemical pesicides, hen a large benefi is a reurn o
arm land o oher uses, such as oress and/or prairies
and conservaion o naural areas, as well as residences
or a burgeoning populaion.
Wha is more, he aggregae economic benefis
associaed wih pesicide use have been subjeced o
various empirical modeling exercises and expressed
as he loss o producion i pesicides were no used
(NC 2000). Producion losses during he mid-1980s
were esimaed o be as high as 37% o oal oupu
(Pimenel e al. 1992). Tis esimaed loss occurred
despie pesicide use, bu he esimae seems raher
high when assessed agains specific crop analyses. For
example, one o he mos desrucive pess o poaoes,
lae bligh disease, broke ou in he Columbia Basin o
Washingon Sae and Oregon during 1995. Fungicide
use rose rom ypically wo applicaions per season oas many as 12 (Johnsoneal. 1997). However, yield
differences beween he pre- and pos-bligh oubreak
were only 4-6 percen. On he oher hand, wihou any
managemen, he bligh epidemic could have reduced
yields 30-100 percen.
Oher economic analyses have projeced he e-
ec on resh and processed vegeable and rui yields
i pesicide use were reduced 50 percen or simply
no used a all (nuson e al. 1993). educions
in resh rui yields were 40 percen and 75 percen,
respecively. Subsanial reducions were projeced in
grain producion under condiions o no herbicide
use (Fernandez-Cornejo e al. 1998). Anoher sudy
esimaed ha a oal pesicide use ban would require
an addiional 2.5 million acres o vegeable and rui
producion o make up or he yield loss (aylor
1995). Alhough modeling esimaes o he impacs
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8
Pest ic ides wi th Benef i ts for Al l : An Agricul tural Perspect ive
by cerified organic growers. For example, spinosad
insecicide, a complex macrocyclic lacone saccharide
derived rom a bacerial ermenaion culure, is used
by odays cherry growers regardless o heir produc-
ion philosophy. Even hough NOSB policy ends oavoid subsances ha are oxic, spinosad has a bio-
chemical mode o acion ha would classiy i as a ype
o neurooxin (Sparks e al. 2001; Orr e al. 2009).
Te puriy o organic ood is urher dispelled
by analyical surveys o organic commodiies o reveal
ha some conain synheic pesicide residues boh
banned and currenly regisered, albei much less re-
quenly han so-called convenional oods (Baker e
al. 2002). esidues in organic commodiies are likely
inadveren, due o airborne ranspor and deposiion,
as well as soil residues rom pas use. ecognizing
he ubiquiy and mobiliy o environmenal residues,
NOP rules allow inadveren pesicide residues up
o 5 percen o he esablished ederal olerance level
wihou a loss o organic cerificaion. Wheher one
likes or dislikes pesicide use, pas pracices influence
residues in ood. However, curren residue sudies
indicae ha he vas majoriy o convenional oods
have no detectable pesticide residues (FDA 2009;USDA AMS 2009).
In summary, various economic analyses are in
agreemen ha pesicide use has been definiely as-
sociaed wih profiable reurns o armers (and hus
o sociey), and i is no rue ha pesicides are used
on every crop indiscriminaely. Te realiy is ha
some crops require disproporionaely more herbicide
use and some crops require more insecicide and/or
ungicide use. Tus, effors o globally limi pesicide
use ail o ake ino accoun specific and local needs
or crop proecion. Furhermore, cerified organic
producers have an array o pesicides hey can use un-
der he rules o he NOSB. Pas land pracices have led
o deecions o pesicide residues in organic ood, bu
curren analyical surveys show ha so-called conven-
ionally produced ood mos ofen has no deecable
pesicide residues.
in he pome rui indusry is mosly done by chemical
hinners bu sill requires some hand hinning i loads
are deemed excessive.
Perhaps he mos popular misconcepion among
consumers o organic oods is ha such producs lackpesicide residues and oher addiives. Te basis or
his belie is he ofen-repeaed argumen ha organic
agriculure disinguishes isel rom convenional
producion mehods because no synheic pesicides
are used. Prolonged pronouncemens o no synheic
pesicide use easily evolve ino a consumer percepion
o no pesicide use. Conracion o no synheic use
o he equivalency o no use a all may be aciliaed
by he myh ha somehow synheic subsances are
generically differen in heir adherence o hermody-
namic laws and reaciviy han naural subsances.
Te realiy is ha U.S. rules or cerificaion o
organic producion allow or he willul use o ap-
proved crop proecion producs. Under he Federal
Insecicide, Fungicide, and odenicide Ac (FIFR)
many o heses producs are legally pesicides and
mus be regisered wih EPA (Felso and acke
2007). However, organic growers by rule canno use
synheic maerials unless approved by he NaionalOrganic Sandards Board (NOSB). Bu no pesicide
(NOSB-approved or oherwise) can be used in any
ype o arming pracice unless veted by EPA firs.
EPA does a comprehensive risk assessmen on all
chemicals submited or regisraion, using he raw
daa submited by a prospecive pesicide regisran.
Similarly, NOSB conracs wih he Organic Maerials
esearch Insiue (OMI) o do a comprehensive
hazard assessmen o maerials proposed or cerified
organic producion. In ha case, similar quesions
are asked, excep ha he OMI speculaes wheher
a candidae produc is really needed and hereore a
credible subsiue. One crierion would be ha i is
less hazardous. Alhough a perspecive o hazard di-
ers rom one ha uses hazard along wih exposure o
characerize risk, some o he acive ingrediens used
by nonorganic growers are he same as hose used
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Pest ic ides & Heal th: Myths vs . Real i t ies
Te inorganic pesicides used during he firs hal o
he 20h
cenury and he firs wave o synhesized pesi-cides afer 1950 were generally broad specrum bu no
necessarily adequae or all cropping sysems (Sern e
al. 1959). Over he las hiry years new chemisries
have been inroduced o narrow he specrum o ac-
iviy. Along wih new ormulaions and applicaion
mehods, modern pesicides can be beter ailored o
specific crops pes problems. Similarly, insecicides
inroduced over he las 15 years are also much less
oxic o he naural bioconrol organisms han he
broad-specrum synheics inroduced during he1950s. Furhermore, modern pesicides rapidly de-
grade in he environmen and do no bioaccumulae
in lipid issues as did he chlorinaed hydrocarbon and
cyclodiene pesicides ha were heavily used prior o
heir ban in he early 1970s.
A ourh benefi sems rom herbicide use in grain
producion hroughou he Corn Bel. Beore he ad-
ven o synheic chemical herbicides like arazine, ero-
sion was severe on even genly sloping lands becausearmers relied on he moldboard plow and urher
culivaion o he soil during crop growh o conrol
weeds. Many environmenal scieniss agree ha eu-
rophicaion and sedimenaion o aquaic resources
due o runoff and erosion rom agriculural land is he
mos imporan cause o waer qualiy impairmen,
no o menion being reponsible or ransporaion
problems as rivers backfill wih sedimen. By he
1960s, a ew herbicides were commercially available
In addiion o heir economic benefis accruing
rom he objecives or which hey are used, pesicideshave cerain advanages over oher pracices or crop
proecion (as well as producion) ha make hem very
convenien, efficien, and cos-effecive (Mecal and
Luckman 1975). Firs, or mos cropping sysems, pes-
icides are he only pracical available echnology be-
cause oher echnologies are no available, unproved,
or do no work efficienly. For insance, hybrids o cer-
ain crops may lack a pes-resisan culivar. In oher
cases, a nonchemical pes conrol pracice ails o work
over ime. An example o he later siuaion is he ap-paren adapaion o wesern corn rooworms o he
pracice o annual corn-soybean roaions ha were
very successul in reducing he need or soil inseci-
cides (Sammons e al. 1997; ondon and Gray 2004).
Second, pesicides have rapid curaive acion in
prevening loss o crop yield or proecing human and
animal healh. Tus, hey can be used when a pes
populaion becomes inolerable. One o he enes
o inegraed pes managemen (IPM) is eschewingprophylacic sprays in avor o as needed reamens.
Tus, here may be a very shor window o ime during
which he pes needs o be conrolled, and nonchemi-
cal mehods may lack a rapid enough acion.
Tird, he diversiy o locaions where crops are
grown means differen pes complexes hrive under
a wide range o climaic condiions. Pesicides have
a wide range o properies, uses, and mehods o ap-
plicaion ha can cover many problems as hey arise.
Agricultural Reality: Practical & EnvironmentalAdvantages of Crop Protect ion Chemicals
The diversity of locations where crops are grown means different
pest complexes thrive under a wide range of climatic conditions.
Pesticides have a wide range of properties, uses, and methods
of application that can cover many problems as they arise.
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Pest ic ides wi th Benef i ts for Al l : An Agricul tural Perspect ive
lands available or wildlie conservaion (Cooper and
Dobson 2007). Direc conrol o human and livesock
pess (as discussed in he ollowing secions) creae
similar secondary benefis or economic produciviy,
public healh, and longeviy.An analysis o hisorical and conemporary man-
agemen o coton pess provides anoher affirmaion
o he benefi o pesicide echnology and also sug-
gess indirec benefis beyond a specific crop (Naranjo
and Ellsworh 2009). Coton has hisorically been a
crop requiring arguably he highes per acre inensiy
o pesicide use. Coton pes managemen in Arizona
has evolved ino a highly sraegic sysem ha employs
boh naural biological conrol organisms (i.e., preda-
ors and parasioids) bu also relies on highly selecive
insecicides or conrolling he mos imporan pess,
which include he pink bollworm and whieflies.
Pink bollworms have been managed by use o coton
culivars bred o conain he highly selecive bace-
rial oxin proein derived rom he naurally occurring
insec pahogen Bacillus huringiensis. Deploymen
o such culivars can conserve predaor populaions.
Te whiefly, on he oher hand has, been successully
managed by judicious inegraion o highly seleciveinsecicides ha affec insec developmen. Te avail-
abiliy o such insecicides has no only increased pro-
is by reducing he overall need or pesicides, i has
also indirecly benefied oher regional crops atacked
by whieflies: Tese now show an overall reducion in
heir populaions. Tus, innovaive pesicide echnol-
ogy has resuled in an unprecedened sabiliy o eco-
sysem services and major economic and environmen-
al gains in Arizona coton ha has exended o benefi
he enire agroecosysem o he region (Naranjo and
Ellsworh 2009).
and allowed armers o consider subsiuing chemical
conrol o weeds or urning he soil over and hereby
making i highly suscepible o he erosion caused by
wind and spring rains on bare soil. No-ill agriculure
bloomed, especially in corn producion, because arm-ers were able o rely on herbicides. Aggregae soil ero-
sion rom illed soil in our Corn Bel saes (Illinois,
Indiana, Iowa, Nebraska) was esimaed a 14.9 ons/
acre/year bu only 2.8 ons/acre/year rom unilled
grain fields (Gianessi and eigner 2006).
Furhermore, by eliminaing he need o ill soil,
herbicides also allow or he conservaion o uel. Over
111 million gallons o uel may be saved by using her-
bicides insead o illage in he aoremenioned our
Corn Bel Saes (Gianessi and eigner 2006). Low-
ered emissions o greenhouse gases are also associaed
wih a reducion in uel use (oberson e al. 2000).
In addiion o uel reducions, an increased yield
or every dollar invesed in agriculural producion
significanly reduces per acre increases in carbon emis-
sions; his is by virue o avoiding he land clearing
oherwise necessary o mainain sufficien producion
or an increasing populaion (Burney e al. 2010).
Tus, curren analyses suppor he idea ha pesicideechnology also conribues o environmenal qualiy
by virue o enhancing yield.
wo oher recen analyses also suppor he con-
clusion ha here are boh direc and indirec benefis
o pesicide echnology. Alhough he direc benefis
o suppression o pes densiy, and hus suppression
o damage, are obvious, indirec benefis can also be
considerable. Some examples o he later include
increased financial resources or a communiy, due
o greaer producer profis; increased consumer ac-
cess o resh ruis and vegeables; and an increase in
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on a coninen like Arica, where publicly financed
programs are inrequen, and poor when hey exis.
Anophelesmosquioes oday sill ransmi per annum
over 500 million cases o malaria (WHO 2010), a
disease caused byPlasmodium falciparum, a prois re-
quiring boh he mosquio and human body in which
o complee is lie cycle. Malaria causes paroxysms
o ever, ofen several imes each day. Wih so many
ineced, economies become inefficien as workers are
sruck ill. And because inan and child nuriion is
so deficien in hese counries, a nearly unimaginable
800,000 children die rom mosquio-ransmited ma-
laria each year.
Bu many counries have malaria under conrol.
Tey adoped he use o DD, he chemical echnol-
ogy used by he miliary during WWII and by he
European Command afer he war o conrol mos-
quio populaions. Daa on malaria incidence beore
and afer he adven o DD proved ha he pesicidecould be effecive wihou causing acue harm (Hayes
1991). Te evidence or lack o acue harm became
apparen when millions o Europeans were direcly
dused o conrol lice ha ransmited a orm o yphus
caused by he bacerium Ricketsia.
However, DD was essenially banned in he U.S.
in 1972 when he recenly-creaed EPA decided o
Daily lie in he developed counries o he Wes
is no likely plagued by insec-ransmited inecious
diseases. While i is rue ha he yellow ever vecor
mosquio Aedes aegypi once hauned he srees o
New Orleans, a program o publicly financed mosqui-
o conrol arose in he 1960s and spread hroughou
he U.S. o dampen he disease-ransmission poenial
o insecs. Even so, over he las decade, Wes Nile
virus, ransmited by he bie o he Culex mosquio,
has spread rom New York o Caliornia, becoming
endemic in every sae (Arsob e al. 2009). Lyme dis-
ease, a spriochee bacerium ransmited by he bie o
he iny deer ick, disables nearly 20,000 people each
year (Bacon e al. 2008); i is in many places now in
he U.S., alhough he epicener is in New England.
Insec bies are mosly a nuisance o ciizens in highly
developed counries, bu he las decade o Wes Nile
virus epidemiology shows he need or vigilance abou
inecious disease conrol even as megaciies and ex-urbs pave over widening expanses o naural lands.
Furhermore, he widespread oubreak and spread o
Wes Nile virus has had observably negaive impacs
on bird populaions (LaDeau e al. 2007).
ecen experience indicaes he need or vigilance
agains arhropod-vecored diseases even in devel-
oped counriesbu he siuaion is surely more dire
Pesticides with Benets for All:A Public Health Perspective
Myth: Pesicides offer no benefi o public healh and, arguably, derac rom i.
The Public Health Reality: Historical and Modern
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Pest ic ides wi th Benef i ts for Al l : A Publ ic Heal th Perspect ive
Mosquio larval, egg-laying, and breeding habia
mus be moniored and managed. Wesern counries
now use insecicides based on microbial oxins, name-
ly Bacillus huringiensis israeliensis (Bi) and Bacillus
sphaericus.BiandB. sphaericusare incredibly specific,naurally occurring baceria ha are oxic only when
ingesed by mosquio larvae. Tese organisms are sill
deemed pesicides, specially regulaed under EPAs
biopesicides program (EPA 2010).
In addiion o habia managemen or mosquio
conrol, individuals are encouraged o proec hem-
selves wih mosquio neting around heir beds a
nigh. Emphasis has been placed on using insecicide-
impregnaed bed neting, which can be effecive when
whole communiies are included in conrol programs.
However, even such relaively passive conrol mea-
sures are very much influenced by he ype o insec-
icide deployed (e.g., irrian vs. non-irrian effecs)
(Curis and Mnzava 2000), urher illusraing ha he
benefis o pesicides depend on he appropriae use o
specific chemicals.
One aspec o proecing public healh ha is
no ofen menioned is he poenial o pesicides o
reduce microbial conaminaion and he associaedproducion o ungal oxins. Overlooked is he use o
chlorine and oher disinecans, all o which are reg-
isered pesicides, in waer reamen. U.S. consumers
appreciae waer devoid o bacerial conaminans and
know implicily ha bacerial inecion rom drinking
waer is very rare here. However, inadequaely reaed
public supplies do occur, as evidenced by he oubreak
o cryposporidium in a Wisconsin waer supply dur-
ing 1993 (Macenzie e al. 1994). A waer-borne ou-
break o pahogenicE. coli in Walkeron, ON during
2000 was also definiively conneced o inadequae
chlorinaion (Hrudey e al. 2003).
Ani-pesicide aciviss may ry o asser ha pes-
icide use is all abou blemish-ree rui and vegeables.
rue, use o crop proecion echnologies reduces
marking and scarring, hereby filling o overflowing
produce couners wih picure-book ood. Bu insec
suspend is regisraion or any agriculural use. (In
ac, he decision was enirely he work o EPAs firs
adminisraor, William uckelshaus.) Unorunaely,
he hisory o agriculural use o DD and is demise
as an effecive pes conrol echnology on crops hasbeen conflaed wih is coninued success wih mos-
quio conrol in lesser developed counries o Arica,
pars o Lain America, and pars o Asia. Alhough
DD was memorialized ino inamy by achel Car-
sons Silen Spring, i was he agriculural use o he
chemical ha go i ino rouble, no he public healh
use. Even so, since Carsons ime, how DD is used in
public healh has been he key o is successul conrol
o mosquioes where hey mater, in he house. During
and shorly afer WWII, spraying o DD was wide-
spread in he environmen. However, by he 1950s i
was well known ha mosquioes resed on walls and
ceilings o buildings. Tus, by he lae 1950s research-
ers had already esablished he efficacy o a space
spray, wherein only resing areas on walls would be
reaed (Barlow and Hadaway 1956).
o his day, he public likely does no undersand
how DD is acually used, and hus visions o Silen
Springdominae he conversaion. So prevalen is hemisundersanding ha a number o counries decided
o eschew is use wih devasaing consequences
or malarial incidence. e-adopion o he limied
spraying o house walls was associaed wih a rapid
decline in malarial incidence (obers e al. 1997).
However, aerial spraying or mosquioes is sill viewed
as effecive under cerain circumsances or some
insec vecored diseases. Te benefis o using aduli-
cides o conrol Wes Nile virus mosquio vecors have
been shown o subsanially exceed coss as well as e-
ecively proec human healh wihou adverse healh
effecs or ecological problems rom pesicide exposure
(Peerson e al. 2006; Davis e al. 2007; Carney e al.
2008; Barber e al. 2010).
Perinenly, public healh proecion specialiss
have long known ha DD alone is no enough o
conrol he scourge o malaria-inesed mosquioes.
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Pest ic ides & Heal th: Myths vs . Real i t ies
are sarling or jus our major Bel Saes alone (i.e.,
Illinois, Indiana, Iowa, Nebraska). Economic analysis
o labor requiremens in he absence o herbicide use
has esimaed he need or a oal o 338 million hours
o work by over wo million workers (Gianessi andeigner 2006). Considering ha less han 2% o he
enire US populaion (approximaely 6 million peo-
ple) works on arms, replacing chemicals wih people
is no pracical.
Perhaps jus as imporan is o quesion how peo-
ple would are doing srenuous physical labor in he
sun or a ypical 8-hour work day. Sun exposure may
explain elevaed lip cancer risks, as well as he slighly
elevaed skin cancer risk, among armers (Aquavella
e al. 1998). Musculoskeleal healh would likely be
seriously impaired, given he physical naure o hand-
pulling and hoeing weeds. As evidence o such physi-
cally adverse impacs, Caliornia insiued an admin-
israive policy prohibiing he use o shor-handled
hoes. Organic letuce growers rely on hand weeding
o atain profiable producion and have peiioned
he Sae o Caliornia agains sricer labor rules,
osensibly because sufficienly effecive approved her-
bicides are unavailable ( James 2005). Tus he lacko appropriae available pesicides adds o labor coss
as i simulaneously raises he issue o hand-weeding
labors impac on worker healh.
Te oregoing sory o public healh benefis now
comes ull circle, back o he hisorical roos o using
pesicides direcly o affec insecs afflicing our bodies.
Te flowers o chrysanhemums (specifically Chysan-
hemum cinerariaefolium) were used in he early 1800s
by Souheasern Europeans and Persians o produce an
exrac called pyrehrum ha alleviaed a lice sufferers
scourge. Tus, over a span o less han 200 years, we
have aken and improved upon Moher Naures chem-
isry o improve our own public healh. W hich leads o
he nex myh abou chemical pesicides.
eeding causes harm ha makes a ood more suscep-
ible o ungal invasion. Cerain ungi commonly
associaed wih crops produce mycooxins ha have
well-documened physiological effecs in mammals,
including humans and livesock (Marasas 2001). Al-lowing insec or plan disease injury o progress wih-
ou proecing a crop only increases he likelihood o
mycooxin residues. Indeed, he problems graviy is
evidenced by an inernaional sandard or maximum
allowable residues o mycooxins. Furhermore, he
value o proecing crops agains direc insec eeding
has been proven wih he adopion o corn geneically
bred wih a gene romBacillus huringiensis(called B
corn) o produce a very insec-specific proein ha
kills he European corn borer. Tis insec damages
corn and is arguably he major cause o ungal myco-
oxin conaminaion, as damaged seed is pushed ino
sorage. Mycooxins are considered boh human and
livesock hazards wih carcinogenic, neurooxic, and
eraogenic effecs. However, B corn has subsanially
lower levels o mycooxin conaminaion han corn no
proeced agains corn borers (Bakan e al. 2002; Wu
2006). Tus B corn, which is regulaed as a pesicide,
helps keep grain qualiy wihin esablished regulaorysandards ha proec agains mycooxin exposure.
One pracical benefi o pesicide use ha is ofen
overlooked is ied boh o public healh proecion o
workers as well as economics o producion. Herbi-
cides, which are used more requenly and in greaer
quaniies han any oher pesicide class, are quickly
applied o all kinds o crops and hus eliminae he
need or hand labor o hoe ou weeds (Gianessi and
eigner 2007). Hand labor is expensive, and is avail-
abiliy is diminished by a shorage o people willing o
become par o a migran worker culure ha moves
rom arm o arm. One applicaion o herbicides or
weed conrol in a single field is worh he hand labor o
ens o hundreds o workers. Te aggregae numbers
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14
ecion agains predaceous proiss or oher baceria.
A perinen example o humans using such hazardous
bacerial meabolies is he subcuaneous injecion or
opical epidermal applicaion o he highly oxic bou-
linim neurooxin, which is derived rom he anaerobic
ood spoilage organism Colsridium boulinin; i is
commonly used or cosmeic or correcive purposes
(Collins and Nasir 2010).
Te examples o aceic acid and boulinin, as well
as oher insances o naural oxins in ood, are bu
some examples o he many incidenal chemicals pro-
duced by plans and/or baceria ha are quie oxic in
high doses. Cerain ungi o he genusAspergillusgrowon cereals and produce chemicals called aflaoxins ha
are hundreds o imes more poen han any synheic
pesicide synhesized by humans. Ye our perspecive
abou he risks o pesicides does no apply oAspergil-
lus, as our concerns are ocused on he imely applica-
ion o a ungicide on sored grainshe righ hing o
do in order o proec ood and aver healh problems.
Many organisms, especially plans, produce chem-
icals incidenal o heir normal energy-producing bio-
chemisry ha uncion o ward off predaors, proec
seeds, or atrac insecs or pollinaion (Ames e al.
1990a, 1990b; Ames and Gold 1997). Someimes,
hese chemicals are jus by-producs o meabolism
ha may serve oher purposes, or hey are perhaps
excreory producs ha would be oxic i allowed o
accumulae in he cells. Someimes we can only specu-
lae abou he evoluionary role o hese chemicals.
For example, apples conain aceic acid. Alhough is
a naural componen o apples, he acid is neverheless
lised as a hazardous subsance, and he MSDS sheeliss horrific adverse effecs rom exposure, including
vomiing, diarrhea, ulceraion, bleeding rom ines-
ines and circulaory collapse. Perhaps he evoluion-
ary benefi o such a meabolic pahway and sorage
in rui accrued rom he known anisepic qualiies o
aceic acid (Levine 1940). Similarly, baceria produce
well-known oxins ha osensibly provide some pro-
Synthetic Chemistry for CropProtection: Humans Imitate
Plants and Bacteria
Myth: Synheic chemical pesicides are unnaural and canno be degraded. Tus,hey are paricularly dangerous in comparison wih naural producs derived romplans.
Technological Reality: Weve A lways C opie dthe Good Ideas of Pl ants and Bacter ia
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Pest ic ides & Heal th: Myths vs . Real i t ies
Humans have always used chemical echnology.
Wheher he chemicals are made by plans, baceria,
or by our own hands is irrelevan. Some have main-
ained here is a difference beween chemicals rom
he ropical rain oress and chemicals rom he gianchemical indusries. Bu principles o environmenal
chemisry would dicae ha behavior o a chemical
is governed primarily by hermodynamics, no how
i was made.
Some would say ha our coevoluion wih plans
over many generaions has allowed us o deoxiy many
o he naural dieary chemicals. Consider, however,
ha many o our oods are recen invenions o selec-
ive breeding ha sill possess he same poenially
oxic chemicals as heir wild ancesors.
In considering synheic pesicides, a credible
argumen can be made or he human use o ools o
synhesize oher useul ools, e.g., pesicides, as an
evoluionary adapaion. Tis adapaion is analo-
gous o he evoluion o secondary meabolic pah-
ways in plans ha resul in biochemicals proecive
o heir survival.
Because chemicals produced by plans are unc-
ional, evoluion has arguably resuled in a orm o
chemical echnology. Trough our own chemical
echnology, aren we jus imiaing our boanical
and bacerial counerpars? For example, Swiss cheeseresuls rom bacerial species ha produce subsanial
amouns o propionic acid when growing on milk
producs. Te propionic acid is a by-produc, along
wih he carbon dioxide ormaion ha creaes he a-
miliar holes, bu i also suppresses prolific ungal (i.e.,
mold) growh (Suomalainen and Mayra-Makinen
1999). oday, humans add synhesized propionaes o
baked goods o obain he same proecion.
Members o indigenous culures have long used
plans as heir medicines. Te knowledge o which
plans o use, how o prepare hem, and he amouns
o adminiser has been passed rom generaion o
generaion. Isn he use o flora or our benefi, our
survival, a orm o chemical echnology? Perhaps we
should consider generaions o rial and error in dis-
covering beneficial and harmul plans as analogous o
a risk assessmen process.
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16
and is one environmenal oxidaion produc, DDE,
drove i o move readily ino he amosphere. Such a
mechanism, commonly called phase pariioning in
he field o environmenal chemisry, was arguably he
mos influenial process in widespread environmenal
disribuion o DD. Unorunaely, is properies o
persisence, along wih broad-specrum biological ac-
iviy agains pess and beneficial insecs (e.g., preda-
ors and parasioids eeding on he pess) alike made
i a poor choice or use in agriculure afer WWII. Add
he rapid developmen o insecs resisan o is effecs,
and he sage was se or enomologisslong beore
he publicaion o Silen Springo recommend ha i
no be used on field and orchard crops.
Evidence o he dynamic naure o indusrys re-
sponse o changing pes-conrol needs, and hus is
abiliy o synhesize and es new chemical designs, is
a new group o chemicals called organophosphorus(OP) insecicides ha were inroduced ino commer-
cial agriculure in he lae 1960s. Soon hereafer, a sec-
ond group, called mehyl carbamae (CB) insecicides,
was inroduced. OP and CB insecicides had shor
persisence in he environmen, and a leas some
were no quie as oxic o predaors and parasioids.
A he very leas, hey gave growers more opions or
Te argumens se orh in his repor by no means
deend he properies o DD as ideal. aher, he
aoremenioned discussion ocused on DDs effecive-
ness in conrolling resing adul mosquioes when he
compound is used in a very specific and locally confined
manner inside o a dwelling. Furhermore, i is used
no solely bu as an adjunc o pyrehroid insecicide-
impregnaed mosquio neting. Ideally, governmen-
unded programs o habia managemen would accom-
pany individuals atemps a mosquio conrol.
All chemicals have disinc physicochemical prop-
eries ha make hem behave differenly rom each
oher. Chemicals wih similar srucural elemens, i.e.,
arrangemen o he same aoms, will behave similarly
ye sill possess idiosyncraic properies. Chemicals
having divergen srucural elemens will be even more
unlike one anoher. Tus, o conclude ha all pesicides,
because hey can kill pess, are jus like DD is o seri-ously lack an undersanding o basic chemisry, no o
menion he complexiy o biochemical ineracions.
Te specific physicochemical properies o DD
ha made i unique were very low waer solubiliy (i is
pracically insoluble in waer) and resisance o exen-
sive degradaion in organisms or on plan suraces. On
he oher hand, he very low waer solubiliy o DD
Youve Come a Long Way, Baby
Myth: Pesicides used oday are all jus like DD, and hus jus as dangerous. Allpesicides are alike and have no changed since DD. All synheic chemicals areequally hazardous.
The Reality of Modern Pesticide Technology:Dynamics & Evolution
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Pest ic ides & Heal th: Myths vs . Real i t ies
o he naural pyrehrins. By he lae 1970s, new insec
growh regulaors were synhesized based on naural
hormones or plan meabolies ha exhibied eiher
juvenile hormone agonisic or anagonisic aciviy
(Menn and Henrick 1981). Te later endeavors wereenhanced by basic research on specific biochemical
and physiological sysems o pess. Te second orm
o bioraional design was he combinaion o more
radiional synhesis mehods wih he opimizaion
o srucure-aciviy relaionships, which occasionally
resuled in compounds ha could affec specific physi-
ological mechanisms o insec pess. For example, an
array o compounds have been synhesized based on
he model compound diflubenzuron, serendipiously
ound o inhibi he synhesis o chiin in he insec
exoskeleon (Menn 1980). Tese ypes o compounds
are sill being used oday, and more recen discover-
ies o heir effecive use as ermiicides have won EPA
Presidenial Green Chemisry Awards. Many o hese
compounds wih effecs on specific insec physiologi-
cal sysems could be used a low raes per acre, owing
o heir poen effecs on he pess even beter, heir
impacs on predaors were low, because hey have o
be direcly eaen or maximal biological effec.Te idea o a silver bulle, as exemplified by
DDs deploymen and overuse in agriculure, had
disappeared rom he mindse o indusrial research
by he mid 1980s; his was because new discoveries o
chemicals wih compleely differen modes o acion
coninued unabaed. Te new bevy o chemicals since
he lae 1980s evenually were recognized by EPA as
meeing heir crieria or reduced risk (EPA 1993).
Tese chemicals were ulimaely used a lower use
raes han many oher chemicals previously markeed,
and hey were even less oxic o mammals, birds, fish,
inegraing chemical use wih biological conrol (Sern
e al. 1959).
As DD and relaed compounds ell ino disavor
in agriculure, and pressure rom regulaory decisions
mouned, growers became heavily relian on OP andCB insecicides. Overreliance on one echnology ofen
leads o pes resisance, bu again he dynamic naure
o he echnology shone: Te Briish had sared work-
ing on modiying he naural insecicidal componens
o pyrehrum exracs, i.e., he pyrehrins, o produce
ligh-sable compounds, and hus longeviy in he field
beyond a ew hours. Forunaely, such compounds
were ar less oxic han he OPs o mammals, which
is always o concern or worker healh, as well as or
birds. Unorunaely, fish were quie suscepible o he
new synheic derivaive o he naural pyrehrins
jus as hey were o he naural producs. However, he
amouns used dropped rom wo or more pounds ap-
plied per acre o ranges o 0.1-0.2 pounds per acre. Ap-
propriae iming o applicaion, combined wih good
soil managemen pracices o proec agains erosion,
could resolve he likelihood o runoff ino aquaic hab-
ias in sufficien quaniies or fish kills. Tus anoher
chemical wih a differen mode o biochemical acionwas added o he growers oolbox. Unorunaely,
overreliance on a paricular chemical again resuled in
developmen o resisan insecs.
By he ime o pyrehroid developmen, inseci-
cide manuacurers had begun o ocus on he concep
o bioraional design o chemicals wih insecicidal
aciviy (Menn and Henrick 1981). Tis concep ook
wo orms. Firs, naural producs wih biological ac-
iviy could be inkered wih, alering heir srucure
o more precisely arge heir aciviy. Developmen o
synheic pyrehroids were iniially based on srucures
The idea of a silver bullet, as exemplied by DDTs deployment
and overuse in agriculture, had disappeared from the mindset of
industrial research by the mid 1980s.
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18
Youve Come a Long Way, Baby
could be applied o a bluegrass lawn or a field o whea
wihou damaging i. Ineresingly, dichlorophenol, a
puaive meabolie o 2,4-D, is synhesized naurally
by a soil ungus and is isomeric analog is used by some
icks as a sex pheromone, as well as an an repellen bya grasshopper species (Gribble 1998). Te discovery
o he specific biological aciviy o 2,4-D reieraes an
imporan concep in biochemisry alluded o beore
seleciviy. Tus, as maniesed by he aoremenioned
evoluion o insecicide chemisry, synheic organic
chemical herbicides invened circa WWII allowed or
biological seleciviy beween animals and plans bu
also wihin he Plan ingdom isel.
By he lae 1950s, he mos inensely used pes-
icide o all ime, arazine, was synhesized and dis-
covered o have only one biochemical effec a field
applicaion raesnamely, inhibiion o a paricular
elecron accepor in Phoosysem II o plans. Ara-
zines poency is selecively limied o broadlea weeds
bu has no aciviy agains grasses like corn. o curail
a long sory, herbicide synhesis coninued o produce
compounds wih oher modes o acion specific o
and aquaic inverebraes (able 2, Figures 2-5). Wih
some excepions, hese chemicals ended o be more
selecive or killing pess raher han predaors. Tus,
even more opporuniy arose or compaibly inegra-
ing hese new chemisries ino programs ha wouldry o deploy ecologically-based, inegraed pes man-
agemen sraegies.
Te hisorical use o herbicides and he evoluion
o chemical classes parallel ha o he insecicides
wih a major excepion. Prior o WWII, abou he only
herbicides available ha could be pracically used on
fields were dinirophenolic compounds like dinoseb
and DNOC. Tese uncouplers o oxidaive phosphory-
laion had a general mechanism o oxiciy ha made
hem nonselecive or weeds, insecs, and ungi. How-
ever, by he 1940s 2,4-D was discovered and ound o
mimic he naural plan hormone auxin (indole-3-aceic
acid), ushering in he discovery o a very specific plan
mechanism o oxic acion. Tus, biological aciviy
a field applicaion raes was only applicable o plans
and no animals. Surprisingly, 2,4-D was only oxic o
cerain dicoyledon (broadlea) plans. Tus, 2,4-D
Table 2. Comparative mammalian toxicity of insecticides registered over the last
decade and designated as reduced risk by EPA.
Active
Ingredient
Commercial
Formulation
Oral LD50
(mg/kg)
Dermal LD50
(mg/kg)
NOAEL
(mg/kg/d)
Azinphos-methyl Guthion 4.4 155 0.149
Chlorpyrifos Lorsban 223 222 0.03
Acetamiprid Assail 1064 >2000 7.1
Indoxacarb Advion 1277 >5000 2
Pyriproxyfen Esteem 4253 >2000 35Methoxyfenozide Intrepid >5000 >2000 10.2
Novaluron Rimon >5000 >2000 1.1
Pymetrozine Fulfil >5000 >2000 0.377
Spinosad Success >5000 >2000 2.7
Rynaxypyr Altacor >5000 >5000 158
o place he concep o reduced risk in perspecive, parameers or azinphos-mehyl and chlorpyrios are shown because hese were
developed prior o EPAs iniiaive, saed in P Noice 93-2 (EPA 1993).
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21
recepor or any ineracion o occur. In addiion o
srucure, molecular ineracions are also influenced
by physicochemical properies relaed o molecular
charges and hydrophobiciy. Such ineracions oc-
cur very readily i he srucures o a oxican and is
recepor are highly complemenary. In such cases, he
subsance is considered highly poen. Ineracionswould occur wih srucures no as complemenary
only under condiions o inordinaely high oxican
concenraions, ypically hose no likely o be ound
in he environmen bu cerainly possible o creae
in he lab when animals are esed. A oxican requir-
ing exremely high concenraions in order o have
an ineracion wih an enzyme or recepor, and hus
cause an adverse physiological reacion, would be
considered o have low poency. In summary, hen,
oxiciy is a propery inheren o any molecule, allow-ing i o elici an adverse physiological response when
an organism has specific enzymes, recepors, or oher
macromolecules whose hree-dimensional srucures
are complemenary.
Te naure o undamenal hermodynamic and ki-
neic laws governing chemical ineracions prescribes
ha any molecule could, hypoheically, inerac wih
Ulimaely, consumers wan o know wheher any
echnology is sae. Te concep o chemical saey
among regulaory oxicologiss is undersood no as a
quaniaive uniary concep bu raher as a descripion
o a probabiliy o a reasonable cerainy o no harm.
Te validiy o he concep o reasonable cerainy o
no harm, which is acually more science policy hanscience, depends on a disincion among he erms
oxiciy, hazard, and risk. Disinguishing hese
erms and, moreover, defining hem rom a biochemi-
cal perspecive, is crucial or a raional argumen abou
he naure o pesicide use in modern sociey.
oxiciy is an inheren propery o boh a paricu-
lar molecule (called he subsrae or ligand) and any
organismal enzymes or recepors (issue cell macro-
molecules) ha i can reac or inerac wih. Such in-
eracion resuls in a physiological reacion ha couldbe inimical o he survival o an organism, and hus
he subsrae or ligand would be called a oxican. By
definiion, pesicides are inimical o he lives o pess,
hus pesicides are oxicans. Te concep o inheren
propery reers o he ac ha he hree-dimensional
srucure o any oxican mus be complemenary
o he hree dimensional srucure o an enzyme or
Its Still About the Dose(and Timing)
Myths: Exposure o pesicides resuls in adverse healh effecs. Hazards o pesicidesare equivalen o he risk o adverse effecs.
The Reality of A Modern Biochemical Perspectiveon Toxic ity, Hazard, and Ri sk
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I t s St i l l About the Dose (and Timin g)
reacion o do somehing abou i? We are cauious by
naure and hus wan o be careul when we have knowl-
edge o poenial harm. Te problem is knowing he
appropriae amoun o resources (financial, inellecual,
ec.) o expend on managing wha may be only poen-ial harm, sincebecause hazard is conexuali may
never be maniesed, or i may be maniesed only under
he mos exreme condiions o chemical use.
o judge jus how worried we should be abou a
oxican in he environmen, and hereore allocae
he appropriae atenion o is hazardousness, we
have o undersand he risk o adverse effec. isk is
also conexual, bu a simple definiion is he prob-
abiliy (likelihood) ha adverse effecs would occur
under a specific siuaion or se o condiions. Ofen,
regulaory oxicologiss will express risk as a uncion
o oxiciy and exposure. Tus, risk is he probabil-
iy or likelihood ha he array o known hazards o a
subsance will acually occur i or when an organism
is exposed. I exposure is nonexisen, hen he likeli-
hood o an effec is nil. I exposure does occur, hen
he likelihood o he subsance being a hazard is con-
diioned no only on he dose bu also on he age, gen-
der, and healh o ha organism as well as he specificroue o exposure. Te imporan poin is ha he risk
o adverse effecs afer exposure o a subsance may be
low or high, depending on all he acors affecing he
hazards o ha subsance.
Thresholds
Low levels o exposure, even o a highly poen
oxican, may have a low probabiliy o causing an ad-verse effec. In any case o exposure, wheher hrough
skin conac, inhalaion, or oral ingesion, a number o
physiological processes occur o modulae he dose or
concenraion o oxican arriving a he cellular level,
and hus he probabiliy o ineracion wih enzymes
or recepors. All o hese physiological processes ha
deermine wha amoun o oxican arrives a he sie
o he cell enzymes or recepors is described by phar-
any oher molecule. However, he concenraion o he
wo molecules mus be sufficienly high or he iner-
acion o have any reasonable probabiliy o occurring.
Tis later concep leads o he definiion o hazard.
Hazard describes he poenial o a chemical o causeharm under a paricular se o condiions. In oher
words, oxicans are no inherenly hazardous unless
he conex is conducive o he sufficien ineracion o
he oxican wih he paricular enzymes or recepors
o which i is complemenary. o sudy how chemicals
inerac wih organisms, scieniss in he laboraory
always creae condiions in which he subjec chemical
will be hazardous. Ofen he condiions are concen-
raions (or doses) o chemical sufficien o cause an
observable response in a es populaion o organisms.
I he condiions o he exposure change (or example,
using a very low dose) hen he hazard may change or
simply disappear alogeher.
Experimens repeaedly show ha naural and
synheic subsances a one dose may have no adverse
effecs on an organism, bu a anoher higher dose can
cause harm. Tis concep, requenly called he dose
makes he poison, is he undamenal principle guid-
ing oxicological sudies, and i is discussed in all basicoxicology exbooks. O course, ha popular oxico-
logical aphorism belies more complex ineracions
beween a subsance and is effecs on an organism.
Te dose required o cause deleerious effecs wihin
a populaion o organisms can vary depending on he
roue o exposure (oral, dermal, or inhalaional), he
lengh o ime over which i is adminisered (acue
versus chronic), and he age, sex, and healh o an or-
ganism. Neverheless, he appearance or magniude o
an effec o any subsance is ied o is dose. Hazard,
hereore, can be hough o as a subsances dose-rela-
ed array o possible deleerious effecs on an organism
o a specific age, gender, and healh saus exposed via
oral, dermal, and/or inhalaional pahways.
Should he knowledge ha a subsance is hazard-
ous, i.e., poenially harmul under a specific se o cir-
cumsances, precipiae a corresponding (and urgen)
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23
Pest ic ides & Heal th: Myths vs . Real i t ies
esearchers sudying he ineracion o oxicans
wih whole animals (in vivosudies) or wih animal
issues, cells, and macromolecules (in viro sudies)
atemp o esablish a hreshold or a physiological or
biochemical reacion. Tey use a wide range o doses(exposures) and concenraions. Te hreshold is
ofen repored as an empirical dose level in which no
observable adverse effec (i.e., he NOAEL) occurs.
o deermine he NOAEL, however, he researcher
mus expose an animal o sufficienly high concenra-
ions o see wha a ypical response looks like. Te
dose jus causing a reacion is called he LOAEL
(lowes observable adverse effecs level). For any
one specific response, he proporion o animals re-
sponding orms a monoonic uncional relaionship
wih he dose ha is mahemaically depiced as an
S-shaped curve (Figure 6). For any effec, hereore,
he researcher can esimae he proporion o he
populaion responding o a paricular dose. Similarly,
he researcher can esimae when no responses in a
populaion will occur.
macokineics. Pharmacokineic sudies examine rae
and exen o chemical upake processes ollowing
dermal, oral, and inhalaional exposures. Te amoun
o oxican enering ino he sysemic circulaion
(bloodsream) is sudied and hen ollowed o issubsequen disribuion among all body regions down
o he cellular level. Te oxican amoun changes as i
is degraded by enzyme sysems and excreed (some-
imes unalered) rom he body. Whaever oxican
is lef over rom all hese pharmacokineic processes
arrives a he sie o he poenial enzymes or recep-
ors complemenary enough in srucure o have any
probabiliy o ineracion. Te specific ineracions are
called pharmacodynamics.
Te combinaion o pharmacokineic processes
and he kineics o pharmacodynamic ineracions
may resul in adverse physiological effecs. Generally
speaking, he physiological sysems mos ofen sud-
ied are he nervous and endocrine sysem, alhough
he immune sysem is necessarily included because
hese hree sysems communicae wih one anoher.
Te relaionship can be expressed as he numbers responding o any given dose meric. I he numbers are ransormed o he cumulaive
proporion (i.e., percen) o he populaion responding, hen an S-shaped curve resuls, which can be described by a logisic mahemaical
uncion. A some dose, no measurable response is observed, and his dose is designaed he no observable adverse effec level (NOAEL)
or concenraion (NOAEC). Te LOAEL represens he dose a which an adverse effec is saisically significanly differen rom he
response in he conrol. Te LD50 and ED50 represen he median response in he populaion (i.e., 50% response) or eiher lehaliy
(L) or any oher measured response (E).
Dose (mg/kg)or Concentration (mg/L)
NumbersResponding
50% Response (median)
PopulationResponse
(Cumulative%)
Dose (mg/kg)or Concentration (mg/L)
100%
50%
0%
Slope
LOAEL
NOAEL
LD50
; LC50
ED50
; EC50
Figure 6. Typical monotonic relationship between increasing dose
(or concentration) and population response.
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I t s St i l l About the Dose (and Timin g)
cal exposure in he environmen (i.e., ouside o he
laboraory).
In summary, hen, he oxiciy o a chemical is an
inheren propery relaed o is srucural abiliy o in-
erac wih some complemenary enzyme or receporin a cell. I he srucures are highly complemenary,
such ha he probabiliy o ineracion is high, hen he
oxican is considered highly poen; bu i srucural
complemenariy is low, he oxican has low poency.
egardless o poency, pharmacokineic processes
modiy he probabiliy o pharmacodynamic inerac-
ions, and hus all oxicans have hresholds or an
effec. Perinenly, hese ineracions and hresholds
apply o all chemicals, naural and synheic, because
all are under conrol o he undamenal laws o her-
modynamics and kineics.
Te ype o experimen ha allows consrucion
o he aoremenioned dose-response curves and de-
erminaion o a no-effecs hreshold alls under he
rubric o regulaory oxicology. Tese experimens
are mos useul or assessing risk o an adverse effecollowing exposure under environmenal condiions.
Furhermore, experimens ha atemp o define a
hreshold or an effec are quie differen in objecive
han experimens ha are designed o undersand
he mechanism o an effec. Tese later experimens
dominae he published oxicology lieraure oday.
However, hose experimens necessarily use high
enough doses so ha an effec is always maniesed
and can hereore be sudied. Alhough inormaive
rom he perspecive o a basic biochemical under-
sanding, mechanisic experimens are no very useul
or characerizing he risk o effecs ollowing chemi-
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consrained by undamenal laws o hermodynamics
and kineics. More specifically, over he las several
decades, oxicological ocus has shifed rom carci-
nogenic responses o endocrine sysem responses.
Whereas he 1950s hrough he 1980s ocused on car-cinogenic mechanisms largely ied o ineracions wih
he genome, during he ime beween he lae1980s
and now, ocus has shifed o chemicals (synheic and
naural) and heir ineracions wih recepors o he
endocrine sysem. A firs, he esrogen recepor, ow-
ing o inense ineres in reproducive biology, was he
objec o mos scruiny, bu now he esoserone (i.e.,
androgen) and hyroid recepors have been hrown
ino he mix.A handul o sudies puaively indicaing ha
chemicals a very low levels o exposure could resul in
endocrine-mediaed aleraions in issues o neonaal
rodens, especially male prosae gland srucure, sug-
gesed ha a new perspecive on oxicans was needed
(vom Saal e al. 1997). O course, ones percepion
o wha consiues a low dose requires empering
by how he dose is adminisered and a query as o
In he hisory o biology, hose remembered by
poseriy are individuals who have creaed a paradigm
shif in hinking abou undamenal lie processes.
Perhaps a he pinnacle o paradigm shifers is Charles
Darwin. Indeed, an ofen-quoed paraphrase is noh-ing in biology makes sense excep in he ligh o evolu-
ion (Dobzhansky 1964), and o course we have Dar-
win o hank or generaing a line o inquiry leading o
he modern heory o biological evoluion. Cracking
he geneic code, ollowing he discovery o he sruc-
ure o DNA, resuled in a plehora o new mehods o
sudy how lie works a he molecular level. O course,
as we sudy differen levels o organizaion, rom cells
o issues o organs o whole organisms, new proper-ies emerge ha are increasingly difficul o describe in
simple molecular erms.
In he conex o biological hisory, perhaps we
shouldn be surprised ha some researchers would
enjoy being called paradigm shifers. However, chang-
ing he ocus o sudy rom one physiological sysem
o anoher is no a paradigm shif, because all possible
ineracions o oxicans in he new sysem are sill
Endocrine Disruption:Is It Just Hormonal?
Myth: Consideraion o endocrine disrupion changes he paradigm o wha weknow abou pesicide effecs. Dose makes he poison is no longer relevan because
pesicides affec he endocrine sysem a levels equivalen o environmenal exposures.
The Reality:Confusion Between a Changing Paradigmand a Shift in Focus, Away from Cancer, to a DifferentPhysiological System
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Endocrine Disrupt ion: Is I t Jus t Hormonal?
are incredibly low i he ligand concenraion is low.
Similarly, ligand-recepor ineracions are reduced
and slowed down as a chemicals poency decreases
(Figure 9). Tereore, no paradigm has really shifed.
ecall he premise ha mechanisic sudies are no de-
signed o show he hreshold level o plausible effecs.
Ye reexaminaion o Figure 7 does show a definiive
hreshold (i.e., a 0.002 g/kg), even or he drug DES,
arguably o similar or greaer poency o esrogen in
binding o he esrogen recepor (Okluicz and Leavit
1988; Hendry e al. 1999, 2004).
wheher he specified dose was chosen, because any
dose lower would no resul in he measured effec a
all. In addiion o observaions o a sligh difference in
male prosae gland weigh beween dosed and conrol
animals (vom Saal e al. 1997), as one example o anendocrine sysem paradigm-changing effec, he dose-
response relaionship accompanying he observaion
was nonmonoonic. In oher words, he observed e-
ecs on gland weigh did no vary in a locksep linear
ashion wih increasing doses (Figure 7). Te high-
es dose caused loss o gland weigh and mid-doses
caused increase in gland weigh. Te validiy o he
conclusions o hese early repors has been quesioned
on grounds o saisical inadequacies (Haseman e al.
2001) or have been judged inconclusive, imprecise,
and o uncerain biological relevance (Melnick e
al. 2002). Neverheless, he problem in inerpreing
nonmonoonic responses arises when wo differen
physiological phenomena are acually being measured
by he same endpoin, such as gland weigh changes.
For example, no pahology oher han gland weigh
changes may occur a low doses, bu a high doses
oxiciy may se in and gland weigh changes are ac-
ually due o a differen phenomenon, such as grealyincreased cell deah.
egardless o he cause o a nonmonoonic re-
sponse (assuming he same physiological response is
acually being measured on each side o he dosage
range), recepor (e.g., esrogen recepor) ineracions
wih ligands (e.g., esrogen or a oxican) are governed
by he principles o biochemical kineics. Tus, he
paradigm has no shifed; concenraion o he ligand
sill influences recepor-ligand complexaion. ineic
analyses o molecule-molecule ineracions can show
he probabiliy o hose ineracions as a uncion o
dose (or concenraion). An illusraion o his con-
cep can help dispel he myh ha low doses rom
environmenal exposures o hormonally acive agens
are inordinaely hazardous. Tus, Figure 8 shows ha
ligand-recepor complexes, he kineic mechanism ini-
iaing a hormonally induced physiological response,
140
120
100
80
60
40
20
00 0.002 0.02 0.2 2 20 200
ProstateGlandChange
RelativetoControl(%)
Diethylstilbestrol Dose (g/kg body weight)
A A
B
B
B AB
C
DES, a drug given o reduce miscarriages during he 1960s, and
also used as a simulaory hormone in catle eed, has a poency
similar in magniude o ha o esradiol. Tis graph is based
on he one presened in vom Saal e al. (1997) ha arguably
iniiaed concerns abou nonmonoonic effecs o hormonally
acive agens. Te daa are shown as percenage change in gland
weigh relaive o he conrol (100%), and he graph has been
rescaled o sar rom zero change. Bars wih he same leters
are no significanly differen rom one anoher (probably