An Introduction To Toxicology and Cancer

1
An Introduction To Toxicology and Cancer
Cancer and Toxins in the Web
Friday Harbor, San Juan Island March 24, 2005
Steven G. Gilbert, PhD, DABT www.asmalldoseof.org
2
Quote / History

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

3
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.

4
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

5
Toxicology Definitions
The study of poisons or the adverse effects of
chemical and physical agents on living organisms.
6
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
7
Key Words
Dose / Response

• Risk
• Hazard X Exposure

Individual Sensitivity
8
What Is This?
O
CH3
CH3
N
N
7
1
3
N
O
N
CH3
9
Effects of Amount on Response
10
Effects of Size on Response
11
Case Studies

• Thalidomide
• Ethanol (Alcohol)
• Methylmercury
• Lead
• PBDEs

12
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• Withdrawn in 1961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

13
What Is This?
(CH3-CH2-OH)
14
FAS Child
15
Lead In Homes
16
CDC Blood Lead Levels
17
The Mercury Cycle
18
Structure of PBDEs
PolyBrominated Diphenyl Ether
X Y are number of Bromine atoms Common Penta,
Octa, and Deca
19
PBDEs in House Dust (ppb)
From EWG - Toxic Fire Retardants Contaminate
American Homes - http//www.ewg.org/reports/inthed
ust/summary.php
20
PBDEs in Breast Milk (ppb)
From EWG - Toxic Fire Retardants in Breast Milk
from American Mothers - http//www.ewg.org/reports
/mothersmilk/es.php
21
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

22
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

23
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

24
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

25
Recent Awareness

• 300 million tons of organic chemical manufactured
  each year
• 100,000 compounds

26
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

27
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

28
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

29
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

30
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

31
Radon US Map
32
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 (lt1-5) Geophysical factors 3
(2-4) Medicines and medical procedures 1
(0.5-3) Industrial Products 1 (lt1-2)
Adapted from Doll and Peto, 1981 Casarett and
Doulls Toxicology, 5th Ed.
33
Cancer Death Rates by Site Male
34
Cancer Death Rates by Site Female
35
Exposure Issues

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

36
Time of Exposure

• During Fetal Development
• Rapidly dividing cells
• Infancy (soy formula?)
• Childhood
• Puberty
• Occupational exposure

37
What causes cancer?

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

38
What causes cancer?

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

39
Genetic Factors

• Breast Cancer ---
• Less 1 in 10 cases in women with a genetic
  predisposition
• Environmental factors?

40
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)

41
Chemical Agents

• Gasoline additives benzene
• Solvents degreasing agents
• Polycyclic aromatic hydrocarbons (PAHs)
• Cigarettes / tobacco products
• Phthalates
• PBDEs?
• PCBs, DDT, DDE

42
Rates of Death Due to Cancer, United States, 1999
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.
43
Cancer Rates in WA (2001)
Washington State Cancer Registry (Adapted from
Kate Davies et al. report (2005))
44
Who are these white guys?
45
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.
46
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)

47
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.

48
What Can We Do??

• Phase out chemicals known to cancer and genetic
  harm
• Educate the public about health effects of
  radiation
• Monitor the chemical body burden and health
  outcomes
• Hold Corporation accountable for hazardous
  practices.
• Enforce existing environmental protection laws
• Practice healthy purchasing
• Adapted the Precautionary Principle

Adapted from - State of the Evidence (3rd ed)
Breast Cancer Fund
49
Cancer and Toxins in the Web
50
Additional Information

• Web Sites
• Breast Cancer Fund - http//www.breastcancerfund.o
  rg/
• 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/

51
Additional Information - WA

• Web Sites
• Breast Cancer Fund WA http//www.breastcancerfun
  d.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

52
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)

53
Authorship Information
This presentation is supplement to A Small
Dose of Toxicology
For Additional Information Contact Steven G.
Gilbert, PhD, DABT E-mail smdose_at_asmalldoseof.org
Web www.asmalldoseof.org
54
Asbestos In the Home
From The White Lung Association web
site http//whitelung.org/pubs/aith/wherefind.html
55
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.
56
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)
57
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

58
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)
59
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)
60
Polluting with HG
Discharge in Minamata Bay
61
Fetal Effects of MeHg
62
PBDEs WA State Status

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