1. A Small Dose of ToxicologyEthics & Prec Prin 2/18/05 A Small Dose of Bioethics Precautionary Principle and Ethical Issues in Toxicology and Risk Assessment Department of Civil and Environmental Engineering Rice University – February 18, 2005 Steven G. Gilbert, PhD, DABT www.asmalldoseof.org

2. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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  Environmental health  Chemicals exposures – human health

3. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Child Health

4. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Vision of Child Health Knowledge of Reproductive and Developmental Toxicology Policy Approach within an ethical framework Social responsibilities No technical solutions Restriction of freedoms Precautionary Principle Convergence of Issues

5. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology WHO Vision for Child Health A World Fit for Children Promoting healthy lives Providing quality education Protecting against abuse, exploitation and violence Combating HIV/AIDS. http://www.unicef.org/why/why_worldgoals.html

6. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology CDC Vision for Child Health “Environmental Health at CDC strives to promote health and quality of life by preventing or controlling those diseases or deaths that result from interactions between people and their environment.” http://www.cdc.gov/node.do?id=0900f3ec8000e044

7. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology American Academy of Pediatrics Mission and vision To attain optimal physical, mental and social health and well-being for all infants, children, adolescents and young adults. http://www.aap.org/member/memcore.htm

8. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology American Academy of Pediatrics The APA goes on to state: “To this purpose, the AAP and its members dedicate their efforts and resources. The vision: 1) to advocate for infants, children, adolescents, and young adults and provide for their care; 2) to collaborate with others to assure child health; and …. http://www.aap.org/member/memcore.htm

9. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology “Children can develop and mature in an environment that allows them to reach and maintain their full potential.” Vision for Child Health

10. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology “Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential.” S. Gilbert (1999) Environmental & Human Health

11. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Dose Response Issues Higher metabolic rate Different nutritional requirements Rapidly dividing & migrating cells Immature organs Susceptibility of Children

12. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Socially responsible white guys?

13. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Socially Responsibility What is social responsibility? What are our responsibilities to society?

14. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology "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

15. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology “An ethic, ecologically, is a limitation on freedom of action in the struggle for existence” Aldo Leopold Limits on Freedom

16. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968

17. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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

18. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Problems – Solutions?  Lead and kids  Fetal alcohol syndrome  Nuclear disarmament  Bioterrorism  Ocean Fisheries  Persistent chemicals  The Commons

19. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Case Studies  Thalidomide  Methylmercury  Lead  Ethanol (Alcohol)  PBDEs

20. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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

21. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Fetal Effects of MeHg

22. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology The Mercury Cycle

23. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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

24. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Lead In Homes

25. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Agency Blood Lead Levels

26. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology FAS Child

27. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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??

28. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Fetal Alcohol Effect (FAE) Milder form of FAS 7,000-36,000 infants per year in US 1 to 3 infants per 1,000 world wide?? Characteristics Growth deficiency Learning dysfunction Nervous systems disabilities

29. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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

30. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Structure of PBDEs X & Y are number of Bromine atoms Common Penta, Octa, and Deca PolyBrominated Diphenyl Ether O Br x Br y

31. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology PBDEs in House Dust (ppb) From EWG - Toxic Fire Retardants Contaminate American Homes - http://www.ewg.org/reports/inthedust/summary.php

32. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology PBDEs in Breast Milk (ppb) From EWG - Toxic Fire Retardants in Breast Milk from American Mothers - http://www.ewg.org/reports/mothersmilk/es.php

33. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968

34. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology "Biology combined with diverse humanistic knowledge forging a science that sets a system of medical and environmental priorities for acceptable survival.“ Global Bioethics (1988) Bioethics -------- 1911 - 2001 -------- Van Rensselaer Potter

35. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology The challenge To develop an individual and societal ethical framework for decision making that supports the long term maintenance of a globally sustainable ecology Genomic and Ecological Bioethics

36. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology The challenge “the knowledge of how to use knowledge for the social good” Knowledgeable Bioethics

37. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology "All scientific work is incomplete - whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have or postpone the action that it appears to demand at a given time. " Sir Austin Bradford Hill (1965) Sir Austin Bradford Hill

38. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 1.Strength of association 2.Consistency of findings 3.Biological gradient 4.Temporal sequence 5.Biologic or theoretical plausibility 6.Coherence with established knowledge 7.Specificity of association Sir Austin Bradford Hill (1965) Determining Causation

39. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology  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

40. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology “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

41. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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

42. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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

43. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology  Improve decision making  Promote integrated assessments  Promote transparency  Promote sharing of information  Examine alternatives  Examine uncertainties  Encourage discussion among stake holders Purpose/Objectives

44. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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

45. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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

46. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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

47. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Testifying Writing review papers K-12 class room teaching Adding expertise to community groups Education Mentoring Speakers Bureau Socially Responsible Actions

48. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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

49. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology The Potential of Children

50. A Small Dose of ToxicologyEthics & Prec Prin 2/18/05 Ethics and the Precautionary Principle Questions or Comments? Download Presentation from www.asmalldoseof.org

51. A Small Dose of ToxicologyEthics & Prec Prin 2/18/05 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

52. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology 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”

53. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Socially Responsible

54. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Scientific Process Variability Uncertainty

55. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Statistical Model Fundamental Types of Uncertainty

56. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Easiest to examine & reduce Not knowing the exact value of a variable (inter and intra subject variance) Sample size Statistical Uncertainty Reducing Variability

57. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Not fully understanding the relations between variables (mechanism of action) Which variables are most important (high dose vs low dose) Model or System Uncertainty

58. Ethics & Prec Prin 2/18/05 A Small Dose of Toxicology Not knowing the right questions to ask Most sensitive end point “we don’t know what we don’t know” Fundamental Uncertainty