1. Cancer & Toxins – 3/24/05 An Introduction To Toxicology and Cancer Cancer and Toxins in the Web Steven G. Gilbert, PhD, DABT www.asmalldoseof.org Friday Harbor, San Juan Island March 24, 2005

2. Cancer & Toxins – 3/24/05 Quote / History " There is no treatment.“ 1600 B.C. Egypt (comment on breast cancer)

3. Cancer & Toxins – 3/24/05 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.

4. Cancer & Toxins – 3/24/05 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

5. Cancer & Toxins – 3/24/05 The study of poisons or the adverse effects of chemical and physical agents on living organisms. Toxicology Definitions

6. Cancer & Toxins – 3/24/05 “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

7. Cancer & Toxins – 3/24/05 Key Words Risk = Hazard X Exposure Dose / Response Individual Sensitivity

8. Cancer & Toxins – 3/24/05 What Is This? N N N N CH 3 O O 1 3 7

9. Cancer & Toxins – 3/24/05 Effects of Amount on Response

10. Cancer & Toxins – 3/24/05 Effects of Size on Response

11. Cancer & Toxins – 3/24/05 Case Studies  Thalidomide  Ethanol (Alcohol)  Methylmercury  Lead  PBDEs

12. Cancer & Toxins – 3/24/05 Thalidomide  Introduced in 1956 as sedative (sleeping pill) and to reduce nausea and vomiting during pregnancy  Withdrawn in 1961  Discovered to be a human teratogen causing absence of limbs or limb malformations in newborns  5000 to 7000 infants effected  Resulted in new drug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. Cancer & Toxins – 3/24/05 What Is This? C H H HOHC H H (CH 3 -CH 2 - OH)

14. Cancer & Toxins – 3/24/05 FAS Child

15. Cancer & Toxins – 3/24/05 Lead In Homes

16. Cancer & Toxins – 3/24/05 CDC Blood Lead Levels

17. Cancer & Toxins – 3/24/05 The Mercury Cycle

18. Cancer & Toxins – 3/24/05 Structure of PBDEs X & Y are number of Bromine atoms Common Penta, Octa, and Deca PolyBrominated Diphenyl Ether O Br x Br y

19. Cancer & Toxins – 3/24/05 PBDEs in House Dust (ppb) From EWG - Toxic Fire Retardants Contaminate American Homes - http://www.ewg.org/reports/inthedust/summary.php

20. Cancer & Toxins – 3/24/05 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. 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

22. Cancer & Toxins – 3/24/05 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. Cancer & Toxins – 3/24/05  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

24. Cancer & Toxins – 3/24/05  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

25. Cancer & Toxins – 3/24/05 Recent Awareness 300 million tons of organic chemical manufactured each year 100,000+ compounds

26. Cancer & Toxins – 3/24/05 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?

27. Cancer & Toxins – 3/24/05 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. Cancer & Toxins – 3/24/05 Case Studies - Benzene  C 6 H 6 – 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. 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 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

30. Cancer & Toxins – 3/24/05 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

31. Cancer & Toxins – 3/24/05 Radon – US Map

32. Cancer & Toxins – 3/24/05 Environmental Factors and Cancer Deaths Diet35% (10-70%) Tobacco30% (25-40%) Infection10% (?) 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.

33. Cancer & Toxins – 3/24/05 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

34. Cancer & Toxins – 3/24/05 Lung Stomach Colon & 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

35. Cancer & Toxins – 3/24/05 Home environment Current events Workplace School Government Decisions Global and local environment Exposure Issues

36. Cancer & Toxins – 3/24/05 During Fetal Development Rapidly dividing cells Infancy (soy formula?) Childhood Puberty Occupational exposure Time of Exposure

37. Cancer & Toxins – 3/24/05 What causes cancer?  Organic chemicals  Inorganic chemicals  Fiber  Radiation (EMF?)  Hormonal Carcinogenesis  Mixtures – Multiple Exposures

38. Cancer & Toxins – 3/24/05 What causes cancer?  Internal factors hormones immune conditions inherited conditions (genetics)  External factors lifestyle habits (smoking, diet, alcohol) viruses, chemicals, radiation

39. Cancer & Toxins – 3/24/05 Genetic Factors  Breast Cancer --- Less 1 in 10 cases in women with a genetic predisposition  Environmental factors?

40. Cancer & Toxins – 3/24/05 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. 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

42. Cancer & Toxins – 3/24/05 Rates of Death Due to Cancer,* United States, 1999 154.7-193.7194.5-206.5207.8-214.0214.8-236.9 *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.

43. Cancer & Toxins – 3/24/05 Cancer Rates in WA (2001) Type Incidence / 100,000 WA rank nationally County (high) Breast181.71 st femaleSan Juan Lung70.19 th female 30 th male Mason Melanoma37.61 st female 5 th male Pend Oreille Bladder23.724 th female 8 th male Pend Oreille Washington State Cancer Registry (Adapted from Kate Davies et al. report (2005))

44. Cancer & Toxins – 3/24/05 Who are these white guys?

45. Cancer & Toxins – 3/24/05 “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

46. Cancer & Toxins – 3/24/05  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

47. Cancer & Toxins – 3/24/05 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

48. Cancer & Toxins – 3/24/05 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 (3 rd ed) – Breast Cancer Fund

49. Cancer & Toxins – 3/24/05 Cancer and Toxins in the Web

50. 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/

51. Cancer & Toxins – 3/24/05 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

52. 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)

53. Cancer & Toxins – 3/24/05 Authorship Information For Additional Information Contact Steven G. Gilbert, PhD, DABT E-mail: smdose@asmalldoseof.org Web: www.asmalldoseof.org This presentation is supplement to “A Small Dose of Toxicology”

54. Cancer & Toxins – 3/24/05 Asbestos – In the Home From The White Lung Association web site http://whitelung.org/pubs/aith/wherefind.html

55. Cancer & Toxins – 3/24/05 399 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. Ancient Awareness

56. Cancer & Toxins – 3/24/05 From Romeo and Juliet - act 5 Come 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

57. Cancer & Toxins – 3/24/05 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?

58. Cancer & Toxins – 3/24/05 “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

59. Cancer & Toxins – 3/24/05 “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

60. Cancer & Toxins – 3/24/05 Polluting with HG Discharge in Minamata Bay

61. Cancer & Toxins – 3/24/05 Fetal Effects of MeHg

62. Cancer & Toxins – 3/24/05  HB 1488 &SB 5515 Prohibiting the sale of products that contain polybrominated diphenyl ethers. PBDEs – WA State Status