Cancer and Toxins in the Web

An Introduction To
Toxicology and
Cancer
Friday Harbor, San Juan Island
March 24, 2005

Steven G. Gilbert, PhD, DABT

www.asmalldoseof.org Cancer & Toxins 3/24/05
 Quote / History

"There is no treatment.
1600 B.C. Egypt
(comment on breast cancer)

Cancer & Toxins 3/24/05

 Incidence of Breast Cancer

A Womens Risk of Breast Cancer (US)

1940s 1 in 22
2004 1 in 7
WHY?
Breast Cancer is leading cause of death in
women ages 34 to 44.

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 Incidence of Breast Cancer
A Womens 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
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 Toxicology Definitions

The study of poisons

or
the adverse effects of chemical and
physical agents on living
organisms.

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 Environmental Health

Conditions that ensure that all

living things have the best
opportunity to reach and maintain
their full genetic potential.

Steven G. Gilbert, 1999

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 Key Words

Dose / Response
Risk =
Hazard X Exposure
Individual Sensitivity
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 What Is This?
O
CH3
CH3
N
N 7
1

3
O N
N
CH3
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Effects of Amount on Response

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Effects of Size on Response

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 Case Studies

Thalidomide
Ethanol (Alcohol)
Methylmercury
Lead
PBDEs

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 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Withdrawn in 1961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

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 What Is This?

H H

H C C OH

H H
(CH3-CH2-OH)
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FAS Child Cancer & Toxins 3/24/05
Lead In Homes

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CDC Blood Lead Levels

Acceptable Childhood Blood Lead Levels

40
40
Blood Lead (ug/dl)

35
30
30
25
25
20
20
15
15
10
10
5
0
CDC CDC CDC WHO EPA CDC
1973 1975 1985 1986 1986 1990
Agency and Year

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The Mercury Cycle

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 Structure of PBDEs

PolyBrominated Diphenyl Ether

O

Brx Bry
X & Y are number of Bromine atoms
Common Penta, Octa, and Deca

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 PBDEs in House Dust (ppb)

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

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 PBDEs in Breast Milk (ppb)

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

Cancer & Toxins 3/24/05

 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

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 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

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Human Cancer Awareness

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

Cancer & Toxins 3/24/05

 Animal Cancer Models

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

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 Recent Awareness

300 million tons of organic

chemical manufactured each year
100,000+ compounds

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 What is Cancer?

Cancer is the uncontrolled

multiplication of cells.
Benign cancerous cells are
contained in one place
Malignant cancerous have
spread to other areas

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 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
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 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

Cancer & Toxins 3/24/05

 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 1900s 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
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 Case Studies - Radon
1400s 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

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Radon US Map

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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 Doulls Toxicology, 5th Ed.

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Cancer Death Rates by Site Male
Rates per 100,000 and are age adjusted to the 1970 census population
80

60
Lung

Stomach
40
ColonandRectum

Prostate
20

Pancreas

0
1930 1940 1950 1960 1970 1980 1990

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Cancer Death Rates by Site Female

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

Lung
30 Breast

20
Uterine
Stomach
Colon&Rectum

10
Ovarian

Pancreas
0
1930 1940 1950 1960 1970 1980 1990

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 Exposure Issues

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

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 Time of Exposure

During Fetal Development

Rapidly dividing cells
Infancy (soy formula?)
Childhood
Puberty
Occupational exposure

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What causes cancer?

Organic chemicals
Inorganic chemicals
Fiber
Radiation (EMF?)
Hormonal Carcinogenesis
Mixtures Multiple
Exposures
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 What causes cancer?

Internal factors
hormones
immune conditions
inherited conditions (genetics)
External factors
lifestyle habits (smoking, diet,
alcohol)
viruses, chemicals, radiation

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 Genetic Factors

Breast Cancer ---

Less 1 in 10 cases in women
with a genetic predisposition

Environmental factors?

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Endocrine / Estrogenic

Pharmaceuticals
Steroidal estrogens (NTP & IRAC
lists as know human carcinogen)
Diethylstilbestrol
Chemicals
Pesticides dieldrin, atrazine
Plastic additives
bispenoal-A (BPA)
polyvinyl cloride (PVC)

Cancer & Toxins 3/24/05

 Chemical Agents

Gasoline additives benzene

Solvents & degreasing agents
Polycyclic aromatic hydrocarbons
(PAHs)
Cigarettes / tobacco products
Phthalates
PBDEs?
PCBs, DDT, DDE
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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.
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 Cancer Rates in WA (2001)

Incidence WA rank County

Type
/ 100,000 nationally (high)
Breast 181.7 1st female San Juan

Lung 70.1 9th female Mason

30th male
Melanoma 37.6 1st female Pend
5th male Oreille
Bladder 23.7 24th female Pend
8th male Oreille

Washington State Cancer Registry

(Adapted from Kate Davies et al. report (2005))
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Who are these white guys?

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 Precautionary Principle

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.

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 Safety & Efficacy vs Harm

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)

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 Central components
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.

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 What Can We Do??
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
Adapted from - State of the Evidence (3rd ed) Breast Cancer Fund
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Cancer and Toxins in the Web

Cancer & Toxins 3/24/05

 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/

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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

Cancer & Toxins 3/24/05

 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)

Cancer & Toxins 3/24/05

 Authorship Information

This presentation is supplement to

A Small Dose of Toxicology

For Additional Information Contact

Steven G. Gilbert, PhD, DABT
E-mail: smdose@asmalldoseof.org
Web: www.asmalldoseof.org

Cancer & Toxins 3/24/05

 Asbestos In the Home

From The White Lung Association web site

http://whitelung.org/pubs/aith/wherefind.html Cancer & Toxins 3/24/05
 Ancient Awareness

399 BC Death of Socrates by Hemlock

Socrates 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.

Cancer & Toxins 3/24/05

 Historical Awareness

From Romeo and Juliet - act 5

Come bitter pilot, now at once run on
The dashing rocks thy seasick weary bark!
Heres to my love! O true apothecary!
Thy drugs are quick. Thus with a kiss I die.

Shakespeare (1564-1616)

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What do these have in common?

Hong Kong
Princess Diana
Ambassador to Mexico
Coeur dAlene, Silver Valley, ID
Tacoma
$100 Billion, $65 Billion
Food, noise, dust
11,000 to 689,000 Children

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Paracelsus

All substances are poisons;

there is none which is not a
poison.
The right dose differentiates
a poison from a remedy.

Paracelsus (1493-1541)

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 An Individual View

The sensitivity of the individual

differentiates a poison from a remedy.
The fundamental principle of toxicology
is the individuals response to a dose.

S. G. Gilbert (1997)

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Discharge in Minamata Bay

Cancer &Polluting
Toxins with HG
3/24/05
Fetal Effects of MeHg

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 PBDEs WA State Status

HB 1488 &SB 5515 Prohibiting the

sale of products that contain
polybrominated diphenyl ethers.

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