1. A Small Dose of ToxicologyEthics & Prec Prin 4/11/05 A Small Dose of PP The Precautionary Principle: A method for dealing with uncertainty in science FOSEP Discussion Group UW Health Sciences, Rm. K-450 April 11, 2005 Steven G. Gilbert, PhD, DABT www.asmalldoseof.org LINKLINK

2. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Ethical Perspective Public Health, Ethics and the Precautionary Principle – Its Matter of Policy NOT Resources And Externalized Costs

3. Ethics & Prec Prin 4/11/05 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

4. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Child Health

5. Ethics & Prec Prin 4/11/05 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

6. Ethics & Prec Prin 4/11/05 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

7. Ethics & Prec Prin 4/11/05 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

8. Ethics & Prec Prin 4/11/05 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

9. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Socially responsible white guys?

10. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Socially Responsibility What is social responsibility? What are our responsibilities to society?

11. Ethics & Prec Prin 4/11/05 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

12. Ethics & Prec Prin 4/11/05 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

13. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968

14. Ethics & Prec Prin 4/11/05 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

15. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Problems – Solutions?  Lead and kids  Fetal alcohol syndrome  Nuclear disarmament  Bioterrorism  Ocean Fisheries  Persistent chemicals  The Commons

16. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Case Studies  Thalidomide  Methylmercury  Lead  Ethanol (Alcohol)  PBDEs

17. Ethics & Prec Prin 4/11/05 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

18. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Fetal Effects of MeHg

19. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology The Mercury Cycle

20. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Lead In Homes

21. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Agency Blood Lead Levels

22. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology FAS Child

23. Ethics & Prec Prin 4/11/05 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??

24. Ethics & Prec Prin 4/11/05 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

25. Ethics & Prec Prin 4/11/05 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

26. Ethics & Prec Prin 4/11/05 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

27. Ethics & Prec Prin 4/11/05 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

28. Ethics & Prec Prin 4/11/05 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

29. Ethics & Prec Prin 4/11/05 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

30. Ethics & Prec Prin 4/11/05 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

31. Ethics & Prec Prin 4/11/05 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

32. Ethics & Prec Prin 4/11/05 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

33. Ethics & Prec Prin 4/11/05 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

34. Ethics & Prec Prin 4/11/05 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

35. Ethics & Prec Prin 4/11/05 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

36. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Seattle Precautionary Principle - White Paper A Policy Framework for Adopting the Precautionary Principle Seattle PP Working Group

37. Ethics & Prec Prin 4/11/05 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

38. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Health Indicators in Seattle Obesity Diabetes Asthma Seattle Initiative Public Health Data Watch Report (Vol 5 No. 1, March 2002)

39. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology 59.8% adult Seattle residents are overweight and 14.6% of all Seattle residents are obese. Risk of developing diabetes, hypertension (high blood pressure) and heart disease. Obesity in Seattle

40. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Obesity

41. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Asthma - Diabetes

42. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology What To Do? Health Indicators in Comprehensive Plan Targets for reduction in incidence of diabetes, cancer, low birth weight, asthma

43. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology The Potential of Children

44. A Small Dose of ToxicologyEthics & Prec Prin 4/11/05 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

45. A Small Dose of ToxicologyEthics & Prec Prin 4/11/05 Ethics and the Precautionary Principle Questions or Comments? Download Presentation from www.asmalldoseof.org

46. Ethics & Prec Prin 4/11/05 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”

47. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Socially Responsible

48. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Scientific Process Variability Uncertainty

49. Ethics & Prec Prin 4/11/05 A Small Dose of Toxicology Statistical Model Fundamental Types of Uncertainty

50. Ethics & Prec Prin 4/11/05 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

51. Ethics & Prec Prin 4/11/05 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

52. Ethics & Prec Prin 4/11/05 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