1. A Small Dose of Toxicology Texas A&M – 2/21/05 A Small Dose of Toxicology An Introduction to the Health Effects of Common Chemicals and A Bit of Ethics Steven G. Gilbert, PhD, DABT “A Small Dose of Toxicology” www.asmalldoseof.org College of Veterinary Medicine Texas A&M, College Station February 21, 2005

2. A Small Dose of Toxicology Texas A&M – 2/21/05 A Small Dose of Toxicology See: www.asmalldoseof.org -- smdosesmdose

3. A Small Dose of Toxicology Texas A&M – 2/21/05 Child Health

4. A Small Dose of Toxicology Texas A&M – 2/21/05 Current Bioethical Issues  Check the local news paper  Stem cells (state, national, international)  Genetically Engineered Organisms  Knowing your genes  In vetro fertilization – choosing your child's genes and characteristics  Global warming  Nanotechnology  Chemicals exposures – human health  Environmental health

5. A Small Dose of Toxicology Texas A&M – 2/21/05 Expanding Knowledge of Biological sciences – genomics, stem cells Ability to engineer life Vulnerability of Children Global issues – warming, famine, war Policy Approach within an ethical framework Social responsibilities No technical solutions Restriction of freedoms Convergence of Issues

6. A Small Dose of Toxicology Texas A&M – 2/21/05 Socially Responsibility What is social responsibility? What are our responsibilities to society?

7. A Small Dose of Toxicology Texas A&M – 2/21/05 "A thing is right when it tends to preserve the integrity, stability, and beauty of the biotic community. It is wrong when it tends otherwise." - Aldo Leopold, 1949, A Sand County Almanac The First Bioethicist ---------- 1887 - 1948 ---------- Aldo Leopold

8. A Small Dose of Toxicology Texas A&M – 2/21/05 “An ethic, ecologically, is a limitation on freedom of action in the struggle for existence” Aldo Leopold Limits on Freedom

9. A Small Dose of Toxicology Texas A&M – 2/21/05 “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968

10. A Small Dose of Toxicology Texas A&M – 2/21/05 Technical Solutions “It is our considered professional judgment that this dilemma has no technical solution.” The Tragedy of the Commons By Garrett Hardin, Science, 1968

11. A Small Dose of Toxicology Texas A&M – 2/21/05 Problems – Solutions?  Lead and kids  Fetal alcohol syndrome  Nuclear disarmament  Bioterrorism  Ocean Fisheries  Persistent chemicals  The Commons

12. A Small Dose of Toxicology Texas A&M – 2/21/05 The study of poisons or the adverse effects of chemical and physical agents on living organisms. Toxicology Definitions

13. A Small Dose of Toxicology Texas A&M – 2/21/05 399 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

14. A Small Dose of Toxicology Texas A&M – 2/21/05 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

15. A Small Dose of Toxicology Texas A&M – 2/21/05 “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

16. A Small Dose of Toxicology Texas A&M – 2/21/05 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?

17. A Small Dose of Toxicology Texas A&M – 2/21/05 Who are these white guys?

18. A Small Dose of Toxicology Texas A&M – 2/21/05 What Is This? N N N N CH 3 O O 1 3 7

19. A Small Dose of Toxicology Texas A&M – 2/21/05 Key Words Risk = Hazard X Exposure Dose / Response Individual Sensitivity

20. A Small Dose of Toxicology Texas A&M – 2/21/05 “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

21. A Small Dose of Toxicology Texas A&M – 2/21/05 “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

22. A Small Dose of Toxicology Texas A&M – 2/21/05 Case Studies  Thalidomide  Ethanol (Alcohol)  Methylmercury  Lead  PBDEs

23. A Small Dose of Toxicology Texas A&M – 2/21/05 Effects of Amount on Response

24. A Small Dose of Toxicology Texas A&M – 2/21/05 Effects of Size on Response

25. A Small Dose of Toxicology Texas A&M – 2/21/05 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

26. A Small Dose of Toxicology Texas A&M – 2/21/05 What Is This? C H H HOHC H H (CH 3 -CH 2 - OH)

27. A Small Dose of Toxicology Texas A&M – 2/21/05 Effects of Prenatal Alcohol

28. A Small Dose of Toxicology Texas A&M – 2/21/05 FAS Child

29. A Small Dose of Toxicology Texas A&M – 2/21/05 Mouse – Scanning EM

30. A Small Dose of Toxicology Texas A&M – 2/21/05 FAS & FAE Most common preventable cause of adverse CNS development Fetal Alcohol Syndrome (FAS) 4,000-12,000 infants per year in US Fetal Alcohol Effect (FAE) 7,000-36,000 infants per year in US 1 to 3 infants per 1,000 world wide??

31. A Small Dose of Toxicology Texas A&M – 2/21/05 1981 - U.S. Surgeon General first advised that women should not drink alcoholic beverages during pregnancy. 1988 - U.S. requires warning labels on all alcoholic beverages sold in the United States. 1990 - U.S. Dietary Guidelines state that women who are pregnant or planning to become pregnant should not drink alcohol. 1998 - 19 states require the posting of alcohol health warning signs where alcoholic beverages are sold Policy Approaches

32. A Small Dose of Toxicology Texas A&M – 2/21/05 Are we doing enough? Given what we know about the fetal effects of alcohol are we doing enough?

33. A Small Dose of Toxicology Texas A&M – 2/21/05 A Small Dose of Lead

34. A Small Dose of Toxicology Texas A&M – 2/21/05 Lead In Homes

35. A Small Dose of Toxicology Texas A&M – 2/21/05 Lead History Greek 2 nd BC Lead Makes the Mind Give Way

36. A Small Dose of Toxicology Texas A&M – 2/21/05 Lead History  6500 BC. - Lead discovered in Turkey, first mine.  500 BC-300 AD.- Roman lead smelting produces dangerous emissions.  100 BC. - Greek physicians give clinical description of lead poisoning. “Lead makes the mind give way.”  1904 - Child lead poisoning linked to lead-based paints.  1922 - League of Nations bans white-lead interior paint; U.S. declines to adopt  1923 - Leaded gasoline goes on sale in selected markets  1971- U.S. Lead-Based Paint Poisoning Prevention Act passed  1923 - Leaded gasoline goes on sale in selected markets  1986 - Primary phase out of leaded gas in US completed

37. A Small Dose of Toxicology Texas A&M – 2/21/05 1990 – lead removed from Gasoline Between 1976 and 1994, the mean blood lead concentration in children dropped from 13.7 mcg/dL to 3.2 mcg/dL One of the major public health triumphs of the 20th century Lead Out of Gasoline

38. A Small Dose of Toxicology Texas A&M – 2/21/05 Lead - Absorption Orally Consumed Lead Absorbed In Place of Calcium CHILDREN – 30-50% OF LEAD ADULTS – 5-10% OF LEAD Increased During Pregnancy

39. A Small Dose of Toxicology Texas A&M – 2/21/05 25 DAYS -- BLOOD 40 DAYS -- SOFT TISSUE 20 YEARS -- BONE Half-life Of Lead

40. A Small Dose of Toxicology Texas A&M – 2/21/05 Lead in Families

41. A Small Dose of Toxicology Texas A&M – 2/21/05 CDC Blood Lead Levels

42. A Small Dose of Toxicology Texas A&M – 2/21/05 Are we doing enough? CDC Lead level 10 to 2 Mcg/dL? Lead in the drinking water of Seattle schools! SB 5189 Reducing childhood lead exposure

43. A Small Dose of Toxicology Texas A&M – 2/21/05 A Small Dose of Mercury

44. A Small Dose of Toxicology Texas A&M – 2/21/05 Polluting with HG Discharge in Minamata Bay

45. A Small Dose of Toxicology Texas A&M – 2/21/05 Fetal Effects of MeHg

46. A Small Dose of Toxicology Texas A&M – 2/21/05 Life-Long Effects of MeHg

47. A Small Dose of Toxicology Texas A&M – 2/21/05 The Mercury Cycle

48. A Small Dose of Toxicology Texas A&M – 2/21/05 Limit the amount of canned tuna you eat, based on your bodyweight. Guidelines are: Women of childbearing age should limit the amount of canned tuna they eat to about one can per week (six ounces.) A woman who weighs less than 135 pounds should eat less than one can of tuna per week. Children under six should eat less than one half a can of tuna (three ounces) per week. Specific weekly limits for children under six range from one ounce for a twenty pound child, to three ounces for a child weighing about sixty pounds. WA State Advisory http://www.doh.wa.gov/fish/FishAdvMercury.htm

49. A Small Dose of Toxicology Texas A&M – 2/21/05 Are we doing enough? Mercury in our fish Restrictions on eating fish

50. A Small Dose of Toxicology Texas A&M – 2/21/05 Structure of PBDEs X & Y are number of Bromine atoms Common Penta, Octa, and Deca PolyBrominated Diphenyl Ether O Br x Br y

51. A Small Dose of Toxicology Texas A&M – 2/21/05 PBDEs in House Dust (ppb) From EWG - Toxic Fire Retardants Contaminate American Homes - http://www.ewg.org/reports/inthedust/summary.php

52. A Small Dose of Toxicology Texas A&M – 2/21/05 PBDEs in Breast Milk (ppb) From EWG - Toxic Fire Retardants in Breast Milk from American Mothers - http://www.ewg.org/reports/mothersmilk/es.php

53. A Small Dose of Toxicology Texas A&M – 2/21/05  Legislation to ban - Penta and Octa-PBDE  Did not ban Deca-PBDE  Must report amount of electronic waste and toxic chemicals in waste such as PBDEs, metals PBDEs – California Status

54. A Small Dose of Toxicology Texas A&M – 2/21/05  HB 1488 &SB 5515 Prohibiting the sale of products that contain polybrominated diphenyl ethers. PBDEs – WA State Status

55. A Small Dose of Toxicology Texas A&M – 2/21/05 Socially responsible white guys?

56. A Small Dose of Toxicology Texas A&M – 2/21/05 “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

57. A Small Dose of Toxicology Texas A&M – 2/21/05  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

58. A Small Dose of Toxicology Texas A&M – 2/21/05 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

59. A Small Dose of Toxicology Texas A&M – 2/21/05 1) Respect - for the needs and rights of this and future generations as well as others who cannot speak for themselves 2) Humility - towards the natural world and our ability to understand it through science 3) Democracy - giving people a voice in matters that affect their lives 4) Responsibility - government’s public trust responsibility to manage the commonwealth for this and future generations. - Individuals’ including industry, obligation to take responsibility for their actions in the world. Values of the precautionary principle

60. A Small Dose of Toxicology Texas A&M – 2/21/05 City Comprehensive Plans Every citizen of Seattle has an equal right to a healthy and safe environment. Seattle sees the Precautionary Principle approach as its policy framework to develop laws for a healthier and more just Seattle. Seattle Initiative

61. A Small Dose of Toxicology Texas A&M – 2/21/05 Children have a right to a safe, fair and healthy environment Ethical Responsibility to share and use of knowledge Duty to promote health and well being of children Thoughtful public health advocate Knowledge - Responsibility

62. A Small Dose of Toxicology Texas A&M – 2/21/05 The citizen toxicologist is a thoughtful advocate for human and environmental health, who strives to share their scientific knowledge with the public, speaking to public interests rather than private or special interests. Citizen Toxicologist Socially Responsible Toxicologist

63. A Small Dose of Toxicology Texas A&M – 2/21/05 Testifying Writing review papers K-12 class room teaching Adding expertise to community groups Education Mentoring Speakers Bureau Socially Responsible Actions

64. A Small Dose of Toxicology Texas A&M – 2/21/05 Forum in which to discuss the ethical implications of results from our science as well as the resulting legal and social implications. 2005 SOT meeting – workshop on Conflict of Interest SOT - ESLI Specialty Section http://www.toxicology.org/memberservices/specsection/specsection.html

65. A Small Dose of Toxicology Texas A&M – 2/21/05 The Potential of Children

66. A Small Dose of Toxicology Texas A&M – 2/21/05 Additional Information  The Science and Environmental Health Network (SEHN) (www.sehn.org)  Late lessons from early warnings: the precautionary principle 1896-2000 – European Environment Agency (free)  Garrett Hardin - The Tragedy of the Commons (Science, 1968)  Ethics and Environmental Health – Mini Monograph - Environmental Health Perspectives (November 2003)  Ethical, legal, and social issues: our children's future. Steven G. Gilbert. Neurotoxicology, in press, 2005

67. A Small Dose of Toxicology Texas A&M – 2/21/05 Principles of Toxicology

68. A Small Dose of Toxicology Texas A&M – 2/21/05 Additional Information A Small Dose of Toxicology www.asmalldoseof.org

69. A Small Dose of Toxicology Texas A&M – 2/21/05 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”

70. A Small Dose of Toxicology Texas A&M – 2/21/05 Dose Response Issues Higher metabolic rate Different nutritional requirements Rapidly dividing & migrating cells Immature organs Susceptibility of Children

71. A Small Dose of Toxicology Texas A&M – 2/21/05 “Children can develop and mature in an environment that allows them to reach and maintain their full potential.” Vision for Child Health