1. ELSI Children 2/28/04 Child Development and Social Responsibility A Small Dose of Toxicology ENVH 517a – Children’s Environmental Health Department of Environmental and Occupational Health Sciences, University of Washington April 19, 2004 Steven G.Gilbert, PhD,DABT

2. ELSI Children 2/28/04 Child Health

3. ELSI Children 2/28/04 Vision of Child Health Knowledge of toxicology Policy Approach within an ethical framework Social responsibilities No technical solutions Restriction of freedoms Precautionary approach Convergence of Issues

4. ELSI Children 2/28/04 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

5. ELSI Children 2/28/04 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

6. ELSI Children 2/28/04 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. ELSI Children 2/28/04 University of Washington The Child Health Institute (CHI) – promotes interdisciplinary collaboration Center for Child Environmental Health Risks Research (CHC) – focus on susceptibility to pesticides http://depts.washington.edu/chc/index.html http://depts.washington.edu/chiorg/

8. ELSI Children 2/28/04 “Children can develop and mature in an environment that allows them to reach and maintain their full potential.” Vision for Child Health

9. ELSI Children 2/28/04 “Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential.” Vision of Environmental Health

10. ELSI Children 2/28/04 Dose Response Issues Higher metabolic rate Different nutritional requirements Rapidly dividing & migrating cells Immature organs Susceptibility of Children

11. ELSI Children 2/28/04 Vision of Child Health

12. ELSI Children 2/28/04 Life – Potential & Harm All life depends on reproduction and development. What effects this process and harms a child's potential?

13. ELSI Children 2/28/04 Terms  Monster – abnormal or strange animal or plant. From Latin monstrum omen, from monere to warn (abnormal infants reflect the future).  Teratology – The study of malformations. From the Greek word for monster – teras.

14. ELSI Children 2/28/04  Reproduction – issues associated with the egg and sperm  Pregnancy – the critical environment of early development  Development of the infant. Three Areas

15. ELSI Children 2/28/04  Many ancient cultures had fertility goddess  Many ancient documentation of malformations  Malformations rich aspect of mythology  6500 BC – Turkey - figurine of conjoined twins  4000-5000 BC – Australia drawings of twins  2000 BC - Tablet of Nineveh – describes 62 malformations and predicts the future Ancient Awareness

16. ELSI Children 2/28/04  15 th -16 th centuries malformations caused by the devil, mother and child killed  1830’s - Etienne Geoffroy Saint-Hilaire experimented with chicken eggs  1900’s began acceptance of malformations related to genetics  1940’s - Josef Warkany – environmental factors affect rat development Historical Awareness

17. ELSI Children 2/28/04  1941 – Human malformations linked to rubella virus  1960’s – Thalidomide (a sedative and anti-nausea drug) found to cause human malformations  1950’s – Methylmercury recognized as developmental toxicant  1970’s – Alcohol related to developmental effects – Fetal Alcohol Syndrome (FAS) Historical Events

18. ELSI Children 2/28/04 50% of pregnancies end in miscarriage or spontaneous abortion often before pregnancy is recognized 15% of couples of reproductive age are infertile Human Reproductive Facts

19. ELSI Children 2/28/04 Fertility Menstrual cycle Sperm count and viability Sexual behavior Reproductive Endpoints

20. ELSI Children 2/28/04  Endocrine disruptors DDT, Dioxin  Heavy metals Lead (decreased sperm)  Organic Solvents Toluene, benzene  Drugs Alcohol Reproductive Toxicants

21. ELSI Children 2/28/04 Cardiovascular Increased - cardiac output heart rate, blood pressure, blood volume expands Oxygen consumption increases by 15-20% Urine volume increases Gut absorption changes Increases in iron and calcium (toxic lead substitutes for calcium) Liver metabolism decreases for some drugs or chemicals (caffeine) Pregnancy Effects the Women

22. ELSI Children 2/28/04  Teratology (physical malformations)  Birth weight  Growth  Neurobehavioral  Decreased intelligence  Decreases learning and memory Developmental Endpoints

23. ELSI Children 2/28/04 Chemicals/Radiation  Chlorobiphenyls  Solvents (Toluene)  Endocrine disruptors  DDT, PCBs  TCDD  X-rays (therapeutic)  Atomic fallout

24. ELSI Children 2/28/04 Infections/Medical Conditions  Rubella virus  Herpes simplex virus  Toxoplasmosis  Syphilis  Diabetes

25. ELSI Children 2/28/04 Plants  Skunk cabbage (Veratrum californicum) – sheep & cattle  Parasites (frogs)

26. ELSI Children 2/28/04 Medical Drugs  Antibiotics (tetracylines)  Anticancer drugs  Anticonvulsants (Valproic Acid)  Lithium  Retinoids (Vitamin A)  Thalidomide  Diethylstilbestrol (DES)  Anticoagulants (Warfarin)

27. ELSI Children 2/28/04 Recreational Drugs  Alcohol (ethanol)  Tobacco  Cocaine  Solvent abuse

28. ELSI Children 2/28/04 Case Studies  Thalidomide  Ethanol (Alcohol)  Methylmercury  Lead

29. ELSI Children 2/28/04 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

30. ELSI Children 2/28/04 Polluting with HG Discharge into Minamata Bay

31. ELSI Children 2/28/04 Fetal Effects of MeHg

32. ELSI Children 2/28/04 Life-Long Effects of MeHg

33. ELSI Children 2/28/04 Hg - Inorganic & Organic Hg CH 3 Inorganic – Quick Silver Hg Organic – Methyl Mercury

34. ELSI Children 2/28/04 The Mercury Cycle

35. ELSI Children 2/28/04 Mercury & Toxicology

36. ELSI Children 2/28/04 Atmospheric Hg

37. ELSI Children 2/28/04 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

38. ELSI Children 2/28/04 Washington State Mercury Chemical Action Plan WA State Advisory http://www.ecy.wa.gov/biblio/0203016.html Legislature saves effort to tackle toxic flame retardants http://www.ecy.wa.gov/../news/2004news/../2004news/200 4-051.html

39. ELSI Children 2/28/04 Alcohol C H H HOHC H H (CH 3 -CH 2 - OH)

40. ELSI Children 2/28/04 Effects of Prenatal Alcohol

41. ELSI Children 2/28/04 FAS Child

42. ELSI Children 2/28/04 Ethanol (Alcohol)  The common preventable cause of adverse fetal development  Fetal Alcohol Syndrome (FAS) first described in 1970’s  Symptoms included facial deformities, growth retardation, sever nervous system effects and reduced intelligence  4,000-12,000 infants per year in US  Fetal Alcohol Effect (FAE) – milder form but still serious nervous system effects

43. ELSI Children 2/28/04 Fetal Alcohol Syndrome (FAS) Most common preventable cause of adverse CNS development 4,000-12,000 infants per year in US Characteristics Growth retardation Facial malformations Small head Greatly reduce intelligence

44. ELSI Children 2/28/04 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

45. ELSI Children 2/28/04 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

46. ELSI Children 2/28/04 Lead History  6500 BC. - Lead discovered in Turkey, first mine.  100 BC. - Greek physicians give clinical description of lead poisoning.  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

47. ELSI Children 2/28/04 "Lead makes the mind give way." Ancient Awareness Greek Dioscerides - 2nd BC

48. ELSI Children 2/28/04 Lead In Homes

49. ELSI Children 2/28/04 Lead in Families

50. ELSI Children 2/28/04 Agency Blood Lead Levels

51. ELSI Children 2/28/04 Lead Health Effects  Children more vulnerable than adults Orally consumed lead absorbed in place of calcium CHILDREN absorb 30-50% of oral lead ADULTS absorb 5-10% of oral lead Increased absorption during pregnancy  Childhood effects Decreased intelligence (lower grades) Hyperactivity (higher school dropout rate) Growth retardation Effects at blood lead levels of 10 µq/dl

52. ELSI Children 2/28/04 Recycling Lead

53. ELSI Children 2/28/04 Risk Assessment Process of estimating association between an exposure to a chemical or physical agent and the incidence of some adverse outcome.

54. ELSI Children 2/28/04 Risk of What? Obvious Death, Cancer, Acid burn, Birth defect, asthma, Subtle Decreases in learning and memory (lead), Sensitivity of the individual (child)

55. ELSI Children 2/28/04 Policy developed to deal with hazards identified through risk assessment Process of evaluating alternative regulatory options and selecting among them Risk Management

56. ELSI Children 2/28/04 “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968

57. ELSI Children 2/28/04 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

58. ELSI Children 2/28/04 Problems – Solutions?  Lead and kids  Fetal alcohol syndrome  Nuclear disarmament  Bioterrorism  Ocean Fisheries  Persistent chemicals  The Commons

59. ELSI Children 2/28/04 Freedom? Hegel – “Freedom is the recognition of necessity” Restriction of Freedom? The Managed Commons?

60. ELSI Children 2/28/04 Business Goals 1.Grow 2.Reduce Costs 3.Increase Revenue

61. ELSI Children 2/28/04 Adam Smith The Wealth of Nations - 1776 “the invisible hand” “an individual who intends only his own gain is led by an invisible hand to promote … the public interest”

62. ELSI Children 2/28/04 Socially responsible white guys?

63. ELSI Children 2/28/04 Scientific Process Variability Uncertainty

64. ELSI Children 2/28/04 Human Epidemiological Human Studies Does the chemical or agent causes adverse effect in human populations?

65. ELSI Children 2/28/04 Pros and Cons - Humans Advantages  Yields information in humans  Yields associations relevant to “real world” exposures Disadvantages  Can be very expensive (large N, many years)  Lack control relative to lab  Many confounding variables

66. ELSI Children 2/28/04 Human Variability Human Subject Variability Lifestyle – risk of exposure to …. Occupation – risk of exposure to …. Breathing & digestion – uptake of chemicals Metabolism & kidney function – elimination Age, gender & disease – susceptibility to toxicity

67. ELSI Children 2/28/04 Examples of Variability Occupational – exposure to multiple chemicals Lung function and susceptibility are altered by smoking or asthma Disease effects liver function The overall dose-response behavior is subject to both intra-individual and inter-individual variability.

68. ELSI Children 2/28/04 Uncertainty Measurements error in experiments Extrapolation from animal studies to human Sample sizes for animal and human studies Selection of endpoint Intra and inter subject variability

69. ELSI Children 2/28/04 “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

70. ELSI Children 2/28/04  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

71. ELSI Children 2/28/04  Precautionary Principle is a tool to assist in an integrated assessment of the human health, environmental issues, scientific facts, uncertainty, and alternatives as well as the ethical, legal and social implications of any decisions. A Tool

72. ELSI Children 2/28/04 Taking preventive action in the face of uncertainty Shifting the burden of proof 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

73. ELSI Children 2/28/04  Improve decision making  Promote integrated assessments  Promote transparency  Promote sharing of information  Examine alternatives  Examine uncertainties  Encourage discussion among stake holders Purpose/Objectives

74. ELSI Children 2/28/04 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

75. ELSI Children 2/28/04 Broad philosophical statement Provides common decision making platform across government departments Something many groups can unite behind – Collaborative on Health and the Environment – (CHE-NW) Advantages of Initiative

76. ELSI Children 2/28/04 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

77. ELSI Children 2/28/04 Testifying Writing review papers K-12 class room teaching Adding expertise to community groups Education Mentoring Speakers Bureau Socially Responsible Actions

78. ELSI Children 2/28/04 The Potential of Children

79. ELSI Children 2/28/04 Socially Responsible

80. ELSI Children 2/28/04 ELSI of Toxicology and Kids Questions or Comments?

81. ELSI Children 2/28/04 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) (http://reports.eea.eu.int/environmental_issue_report_2001_22/en)  Garrett Hardin - The Tragedy of the Commons (Science, 1968)  Ethics and Environmental Health – Mini Monograph - Environmental Health Perspectives (November 2003)

82. ELSI Children 2/28/04 Authorship Information Steven G. Gilbert, PhD, DABT Director, INND 8232 14 th Ave NE Seattle, WA Ph: 206.527.0926 Fx: 206.525.5102 E-mail: sgilbert@innd.org

83. ELSI Children 2/28/04 Biomedical Ethics Respect for Autonomy Nonmaleficence Beneficence Justice Beauchamp and Childress, 1994