Cancer & Toxins – 3/24/05 An Introduction To Toxicology and Cancer Cancer and Toxins in the Web Steven G. Gilbert, PhD, DABT Friday

Cancer & Toxins – 3/24/05

An Introduction To Toxicology and

Cancer

Cancer and Toxins in the Web

Steven G. Gilbert, PhD, DABTwww.asmalldoseof.org

Friday Harbor, San Juan IslandMarch 24, 2005


Quote / History

"There is no treatment.“

1600 B.C. Egypt

(comment on breast cancer)


Incidence of Breast Cancer

A Women’s Risk of Breast Cancer (US)

1940’s – 1 in 22

2004 – 1 in 7

WHY?Breast Cancer is leading cause of death in

women ages 34 to 44.


Incidence of Breast Cancer

A Women’s Risk of Breast Cancer (WA)

ACS 148 per 100,000

WA cancer registry – 181 per 100,000

WHY?This year in WA

4,000 women diagnosed with BC

800 will die of BC

Highest rate in US


The study of poisonsor

the adverse effects of chemical and physical agents on living

organisms.

Toxicology Definitions


“Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential.”

Steven G. Gilbert, 1999

Environmental Health


Key Words

Risk =

Hazard X Exposure

Dose / Response

Individual Sensitivity


What Is This?

N

NN

N

CH3

CH3

CH3

O

O

1

3

7


Effects of Amount on Response


Effects of Size on Response


Case Studies

Thalidomide Ethanol (Alcohol) Methylmercury Lead PBDEs


Thalidomide

Introduced in 1956 as sedative (sleeping pill) and to reduce nausea and vomiting during pregnancy

Withdrawn in 1961

Discovered to be a human teratogen causing absence of limbs or limb malformations in newborns

5000 to 7000 infants effected Resulted in new drug testing rules


What Is This?

CH

H

H

OHC

H

H

(CH3-CH2-OH)

Cancer & Toxins – 3/24/05FAS Child


Lead In Homes


40

30

25

20

15

10

0

5

10

15

20

25

30

35

40

Blo

od

Lea

d (

ug

/dl)

CDC1973

CDC1975

CDC1985

WHO1986

EPA1986

CDC1990

Agency and Year

Acceptable Childhood Blood Lead Levels

CDC Blood Lead Levels


The Mercury Cycle


Structure of PBDEs

X & Y are number of Bromine atomsCommon Penta, Octa, and Deca

PolyBrominated Diphenyl Ether

O

BrxBry


PBDEs in House Dust (ppb)

From EWG - Toxic Fire Retardants Contaminate American Homes - http://www.ewg.org/reports/inthedust/summary.php


PBDEs in Breast Milk (ppb)

From EWG - Toxic Fire Retardants in Breast Milk from American Mothers - http://www.ewg.org/reports/mothersmilk/es.php


Ancient Awareness

• 80 Million years ago – Dinosaur bones show evidence of cancer

• 3000 BC - Egyptian mummies – bone cancer

• 1600 BC – Egypt – 8 cases of breast tumors (or ulcers)Treated by cauterization – with the “fire drill” - Edwin Smith Papyrus


Ancient Awareness

• 300 BC – Hippocrates named tumors as carcinos or carcinoma – tumors spread out like legs of a crab

• 1500 – autopsy start to provide a greater understanding of cancer

• 1650 – more knowledge with advance in medical science tools like the microscope


1700 – Occupational cancer – High incidence of breast cancer among nuns

1775 – Percivall Pott – Occupational – cancer of scrotum in chimney sweeps

1895 – Bladder cancer in workers in aniline dye industry

Human Cancer Awareness


1915 – skin tumors in rabbits treated with coal tar on the skin

1930s – isolation of polycyclic aromatic hydrocarbon from coal tar

1932 – benzo(a)pyrene synthesized 1935 – feeding azo dyes to rats can

cause liver cancer

Animal Cancer Models


Recent Awareness

• 300 million tons of organic chemical manufactured each year

• 100,000+ compounds


• Cancer is the uncontrolled multiplication of cells.

• Benign – cancerous cells are contained in one place

• Malignant – cancerous have spread to other areas

What is Cancer?


Case Studies - Soot

• 1775 – Percivall Pott – Occupational – cancer of scrotum in chimney sweeps

• 1892 – scrotal cancer rare on European content but still high in England – attributed to hygiene

• 1915 – skin tumors in rabbits treated with coal tar on the skin

• 1930s – isolation of polycyclic aromatic hydrocarbon from coal tar

• Now – smoking and organic fuels


Case Studies - Benzene

C6H6 – Clear, colorless, high flammable, vaporizes at room temp

Known human carcinogen – effect bone marrow causing leukemia

Acute inhalation – CNS effects, dizziness In US gasoline 2% benzene but up to 5% in

other countries Metabolized by liver to more toxic metabolites US EPA water standard 0.005 mg/L (5 ppb) US OSHA – 1 ppm in workplace air over 8 hrs


Case Studies - Asbestos

Cause serious lung disease Asbestosis – scarring of the lung Mesothelioma– cancer of lung lining

Known since ancient times – commercial use started in early 1900’s with wide spread use during World War II

Used in 1000s of consumer and industrial products

First heath effects seen in early 1900s Dose response and latency effects established

in 1930s Regulation and banning started in 1970s Millions of people exposed


Case Studies - Radon

1400’s lung disease in miners 1879 – lung cancer in European Miners Colorless, odorless radioactive gas Decay product – uranium to radium to the

gas radon to the solid polonium Polonium sticks to lung tissue – decays

releasing an alpha particle which damages cellular DNA causing cancer

1 in 15 (6%) homes in US elevated Radon U.S. EPA action level 4 pCi/L


Radon – US Map


Environmental Factors and Cancer Deaths

Diet 35% (10-70%)Tobacco 30% (25-40%)Infection 10% (?)Alcohol 3% (2-4%)Reproductive and sexual behavior 7% (1-13%)Occupation 4% (2-8%)Pollution 2% (<1-5%)Geophysical factors 3% (2-4%)Medicines and medical procedures 1% (0.5-3%)Industrial Products 1% (<1-2%)

Adapted from Doll and Peto, 1981; Casarett and Doull’s Toxicology, 5th Ed.


Lung

Stomach

Colon and Rectum

Prostate

1930 1940 1950 1960 1970 1980 1990

Pancreas

80

60

40

20

0

Rates per 100,000 and are age adjusted to the 1970 census population

Cancer Death Rates by Site Male


Lung

StomachColon & Rectum

1930 1940 1950 1960 1970 1980 1990

Pancreas

30

20

10

0

Rates per 100,000 and are age adjusted to the 1970 census population

Breast

Uterine

Ovarian

Cancer Death Rates by Site Female


• Home environment• Current events• Workplace• School• Government Decisions• Global and local environment

Exposure Issues


• During Fetal Development• Rapidly dividing cells

• Infancy (soy formula?)• Childhood• Puberty• Occupational exposure

Time of Exposure


What causes cancer?

Organic chemicals Inorganic chemicals Fiber Radiation (EMF?) Hormonal Carcinogenesis Mixtures – Multiple

Exposures


What causes cancer?

Internal factorshormones

immune conditions

inherited conditions (genetics)

External factorslifestyle habits (smoking, diet,

alcohol)

viruses, chemicals, radiation


Genetic Factors

Breast Cancer --- Less 1 in 10 cases in women

with a genetic predisposition

Environmental factors?


Endocrine / Estrogenic

PharmaceuticalsSteroidal estrogens (NTP & IRAC

lists as know human carcinogen)

Diethylstilbestrol

ChemicalsPesticides – dieldrin, atrazine

Plastic additives –

bispenoal-A (BPA)

polyvinyl cloride (PVC)


Chemical Agents

Gasoline additives – benzene Solvents & degreasing agents Polycyclic aromatic hydrocarbons

(PAHs) Cigarettes / tobacco products Phthalates PBDEs? PCBs, DDT, DDE


Rates of Death Due to Cancer,* United States, 1999

154.7-193.7 194.5-206.5 207.8-214.0 214.8-236.9

*Deaths per 100,000 people, age adjusted to 2000 total U.S. population. Data are grouped in quartiles and ranked from lowest to highest.Source: National Center for Health Statistics, CDC.


Cancer Rates in WA (2001)

TypeIncidence / 100,000

WA rank nationally

County (high)

Breast 181.7 1st female San Juan

Lung 70.1 9th female

30th male

Mason

Melanoma 37.6 1st female

5th male

Pend Oreille

Bladder 23.7 24th female

8th male

Pend Oreille

Washington State Cancer Registry(Adapted from Kate Davies et al. report (2005))


Who are these white guys?


“When an activity raises threats of harm to human health or the environment,

precautionary measures should be take even if some cause and effect relationships are not

fully established scientifically.”

Wingspread Conference, 1998.

Precautionary Principle


FDA regulations of Drugs (1938) FDA regulations of Dietary

Supplements (Dietary Supplement Health and Education Act of 1994 (DSHEA))

Ephedra present an unreasonable risk of illness or injury (Dec, 2003)

Safety & Efficacy vs Harm


• Taking preventive action in the face of uncertainty

• Shifting the burden of proof/responsibility to the proponents of an activity

• Exploring a wide range of alternatives to possibly harmful actions

• Increasing public participation in decision making

Wingspread Conference, 1998.

Central components


1. Phase out chemicals known to cancer and genetic harm

2. Educate the public about health effects of radiation

3. Monitor the chemical body burden and health outcomes

4. Hold Corporation accountable for hazardous practices.

5. Enforce existing environmental protection laws

6. Practice “healthy purchasing”

7. Adapted the “Precautionary Principle”

What Can We Do??

Adapted from - State of the Evidence (3rd ed) – Breast Cancer Fund


Cancer and Toxins in the Web


Additional Information

Web Sites

• Breast Cancer Fund -

http://www.breastcancerfund.org/• The International Agency for

Research on Cancer (IARC) is part of the World Health Organization. - http://www.iarc.fr/

• U.S. National Cancer Institute (NCI). - http://www.cancer.gov/


Additional Information - WA

Web Sites

• Breast Cancer Fund – WA http://www.breastcancerfund.org/washington

• Health & Environmental Contaminants in Washington State – by Kate Davies et al. see www.iceh.org

• Washington State, Department of Health Cancer Registry – www.doh.wa.gov/wscr

• “A Small Dose of Toxicology” www.asmalldoseof.org


Precautionary Principle

Web Sites

• A Small Dose of Toxicology - precautionary principle – www.asmalldoseof.org

• Washington Toxics Coalition – www.watoxics.org

• Ethical, Legal, and Social Issues: Our Children's Future, Steven G. Gilbert (2005) – see www.asmalldoseof.org

• Seattle PP white paper• The Science and Environmental Health

Network (SEHN) (www.sehn.org)


Authorship Information

For Additional Information ContactSteven G. Gilbert, PhD, DABT

E-mail: [email protected]: www.asmalldoseof.org

This presentation is supplement to “A Small Dose of Toxicology”


Asbestos – In the Home

From The White Lung Association web site

http://whitelung.org/pubs/aith/wherefind.html


399 BC Death of Socrates by HemlockSocrates was charged with religious heresy and corrupting the morals of local youth.

The active chemical used was the alkaloid coniine which, when ingested causes paralysis, convulsions and potentially death.

Ancient Awareness


From Romeo and Juliet - act 5Come bitter pilot, now at once run on

The dashing rocks thy seasick weary bark!

Here’s to my love! O true apothecary!

Thy drugs are quick. Thus with a kiss I die.

Shakespeare (1564-1616)

Historical Awareness


• Hong Kong

• Princess Diana

• Ambassador to Mexico

• Coeur d’Alene, Silver Valley, ID

• Tacoma

• $100 Billion, $65 Billion

• Food, noise, dust

• 11,000 to 689,000 Children

What do these have in common?


“All substances are poisons; there is none which is not a

poison. The right dose differentiates

a poison from a remedy.”

Paracelsus (1493-1541)

Paracelsus


“The sensitivity of the individual differentiates a poison from a remedy.

The fundamental principle of toxicology is the individual’s response to a dose.”

S. G. Gilbert (1997)

An Individual View

Cancer & Toxins – 3/24/05Polluting with HG

Discharge in Minamata Bay


Fetal Effects of MeHg


HB 1488 &SB 5515 Prohibiting the sale of products that contain polybrominated diphenyl ethers.

PBDEs – WA State Status

Documents

Cancer & Toxins – 3/24/05 An Introduction To Toxicology and Cancer Cancer and Toxins in the Web Steven G. Gilbert, PhD, DABT Friday