1. Beyond Risk Assessment to Precautionary A Small Dose of Toxicology

2. Beyond Risk Assessment to Precautionary A Small Dose of Toxicology Precautionary Assessment Steven G. Gilbert, PhD, DABT www.asmalldoseof.org www.toxipedia.org Getting Out of the Risk Assessment Box: Precautionary Approaches for Public Health (Critical Analysis of Risk Assessment & Alternative Approaches) How Chemicals Affect Your Health

3. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Risk Assessment "We should remember that risk assessment data can be like the captured spy: If you torture it long enough, it will tell you anything you want to know." (William Ruckelshaus -1st administrator of U.S. EPA 1984.)

4. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Outline Risk Assessment – Arbitrary and Capricious  Vision and Ethics  Principles of Risk Assessment  Risk Assessment - examples  Weaknesses of Risk Assessment  Beyond Risk Assessment to Precautionary Assessment

5. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 “Children can develop and mature in an environment that allows them to reach and maintain their full potential.” Vision for Child Health

6. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 “Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential.” S. Gilbert (1999) Human & Environmental Health

7. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Socially responsible white guys?

8. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 "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

9. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 “An ethic, ecologically, is a limitation on freedom of action in the struggle for existence” Aldo Leopold Limits on Freedom

10. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968

11. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 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

12. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Problems – Solutions?  Lead and kids  Fetal alcohol syndrome  Nuclear disarmament  Bioterrorism  Ocean Fisheries  Persistent chemicals  The Commons

13. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 "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

14. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 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

15. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 “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

16. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Setting goals (Health indicators) Taking preventive action in the face of uncertainty Shifting the burden of responsibility to the proponents of an activity (Who benefits?) Exploring a wide range of alternatives to possibly harmful actions (Is it necessary?) Increasing public participation in decision making (transparency of information & environmental justice) Central components

17. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Key Words of Toxicology Hazard X Exposure = Risk Individual Susceptibility Dose / Response

18. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07  Developed in 1960-1970s  Concern over increased cancer rates  Expanded to non-cancer effects Modern Risk Assessment

19. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 "If someone had evaluated the risk of fire right after it was invented, they may well have decided to eat their food raw." Julian Morris of the Institute of Economic Affairs in London Perspective

20. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Quantitative Risk Assessment Process of estimating association between an exposure to a chemical or physical agent and the incidence of some adverse outcome. National Research Council, Risk Assessment in the Federal Government: Managing the Process. National Academy Press, Washington, DC, 1983

21. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Steps in Risk Assessment  Hazard Identification  Exposure Assessment  Dose-Response Assessment  Risk Characterization

22. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 What Hazard? Obvious Death, Cancer, Acid burn, Birth defect, asthma ….. Subtle Decreases in learning and memory (lead) Loss of potential Sensitivity of the individual (child)

23. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Hazard Identification Review human and animal data to determine if a chemical or agent has biological effects.

24. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Toxicity Endpoints  Carcinogenicity  Mutations  Altered immune function  Teratogenicity  Altered reproductive function  Neuro-behavioral toxicity  Organ-specific effects  Ecological effects (wildlife, environmental persistence)

25. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Exposure Assessment  Route of exposure (skin, oral, inhalation)  Amount of exposure (dose)  Duration of exposure  To whom (animals, humans, environment)  Children, other sensitive individuals

26. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Home environment Workplace (occupational) School Food Consumer products Global and local environment Exposure Issues

27. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Dose-Response Assessment How much exposure to a chemical or agent will cause what effect? Dose – Response

28. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Some Jargon LOAEL – Lowest Observed Adverse Effect Level (mg/kg) NOAEL – No Observed Adverse Effect Level (mg/kg) RfD – Reference Dose (mg/kg-day)

29. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Greater Dose – Greater Response Dose Response Threshold (NOAEL) ED50 LOAEL

30. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07  Hazard (including sensitive populations) –Low dose extrapolation  Exposure –Route of exposure, amount, duration dermal, oral, inhalation, injection –To Whom? Sensitive Individuals? Risk Characterization Risk = Hazard X Exposure

31. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Use of Uncertainty Factors Divide Dose by Power of 10 Human variability Interspecies extrapolation Children Subchronic to chronic extrapolation Absence of a NOAEL Database uncertainty

32. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 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 Socio/economic facts

33. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Doubt / Uncertainty "Doubt is our product since it is the best means of competing with the 'body of fact' that exists in the mind of the general public.“ 1969 an executive at Brown & Williamson owned by R. J. Reynolds Tobacco Company (Doubt Is Their Product by David Michaels in Scientific American, June 15, 2005)

34. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Use of Uncertainty Factors Animal Dose Response Data NOAEL (No Observed Adverse Effect Level) or LOAEL Divide by 10 (Account for inadequate animal data) Divide by 10 (Animal to Human Extrapolation) Divide by 10 (Human Variability or Individual Sensitivity) Reference Dose (RfD) Or Acceptable Daily Intake (ADI)

35. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Mercury & Toxicology

36. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 The Mercury Cycle

37. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Atmospheric Hg

38. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Blindness - Deafness Cerebral Palsy - Seizures Abnormal reflexes & muscle tone Retarded motor development Visual and Auditory Deficits Delayed motor development Human and animal data Neurobehavioral Effects

39. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07  Decrease in Brain Size  Cell loss  Disorganization of cells  Cell migration failures  Behavioral effects – learning and memory Effects On The Brain

40. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Fetal Effects of MeHg

41. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07  MONKEY - 25 µg/kg - LOAEL  RAT - 10 µg/kg - LOAEL  RAT - 50 µg/kg - replicated Animal - Risk Assessment

42. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07  2.5 µg/kg - NOAEL (animals)  0.25 µg/kg - Human  0.025 µg/kg - Sensitive populations Animal - Risk Assessment (the rule of dividing by 10)

43. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 10-20 ppm hair - LOAEL 40-80 ppb blood - LOAEL 0.645 µg/kg 0.06 µg/kg - RfD Human - Risk Assessment Gilbert, S.G., and Grant-Webster, K.S. Neurobehavioral effects of developmental methylmercury exposure. Env. Health Persep. 103(Suppl 6), 135-142, 1995.

44. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 MeHg Consumption Limits US EPA – 0.1 ug/kg-day US FDA – 1 ppm (mg/kg) in tuna

45. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 "Lead makes the mind give way." Ancient Awareness Greek Dioscerides - 2nd BC

46. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Agency Blood Lead Levels

47. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Recycling Lead

48. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Limitations of Risk Assessment  Lack of adequate data  Most sensitive endpoint  Low dose extrapolation  Exposure information  Multiple chemical exposures  Complex – expert driven – undemocratic  Individual sensitivity  Narrow perspective – Ethical??

49. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07  Community / Social Issues  Exposure Issues  Hazard / Toxicity Precautionary Assessment An approach to evaluating the scientific, safety, community, ethical, and social issues related to a compound or procedure.

50. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07  Community / Social Issues  G = Goal  N = Need  F = Future Generations  D = Democratic, community based process  A = Alternatives Precautionary Assessment

51. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Precautionary Assessment InitialParameterScoreComment Community / Social Issues Evaluate effects on the community and related social issues. GG=Goal1-3 1-a lot, 2-some, 3-little. Does this move forward the goal of human and environmental health? NN=Need1-3 1-a lot, 2-some, 3-little or not sure. Ask the question: Is it necessary? Do we really need this? F F=Future Generations1-3 1-little, 2-some, 3-high impact. Is there a potential impact on future generations of humans and other species? D D=Democratic, community based process1-3 1-a lot of community involvement and consultation, 2-some, 3-little. Was the community consulted early and often in the process? Was the process democratic and inclusive. AA=Alternatives1-3 1-alternatives were carefully considered, 2-some consideration, 3-no consideration. Where alternatives considered? Total5-15 5-good, supportive of health and community 15-poor, not supportive of health or community

52. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07  Exposure Issues  E = Exposure  M = Multiple exposures  Ch = Children exposed  CP = Consumer products  O = Occupational exposure  F = Food exposure Precautionary Assessment

53. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Precautionary Assessment Exposure Issues Evaluate potential exposure issues. EE=Exposure0-3 0-none, 1-little, 2-some, 3-high. Do we have control over the exposure? M M=Multiple exposures0-3 0-none, 1-little, 2-some, 3-high. Is there exposure to other chemicals with similar hazard? Ch Ch=Children exposed0,3,5 0-none, 3-little, 5-some or high or don't know. Children are often more vulnerable. Are children being exposed. CP CP=Consumer products0-3 0-not in consumer products, 1-little, 2-some, 3- a lot or do not know. Is this compound in consumer products? O O=Occupationa l exposure0-3 0-no occupational exposure, 1-little, 2-some, 3- a lot or do not know. Is there occupational exposure? F F=Food exposure0-3 0-not in food supply, 1-little, 2-some, 3- a lot or do not know. Is the compound present in the food supply. Total0-20 0-no exposure, no problems 20-significant exposure, serious concern

54. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07  Hazard / Toxicity  H = Hazard  IS = Individual Sensitivity  EC = Ecological hazard  UC = Uncertainty  V = Volume  P = Persistent Precautionary Assessment

55. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Precautionary Assessment Hazard / Toxicity Evaluate potential hazards. HH=Hazard1,5,10 1-low, 5-some, 10-high. Follow classical hazard evaluation, pick endpoint, exam relevant quality studies (cancer, reproductive, neurotoxicity, irreversible) IS IS=Individual Sensitivity1-3 1-little 2-some, 3-a lot. Determine if any individuals are more sensitive than health adult such as the very young or old. EC EC=Ecological hazard1-3 1-little 2-some, 3-a lot. Is it a hazard to other species or the environment? VV=Volume1-5 how much is produced (1=research only, 2= 100,000 or do not know) PP=Persistent1-3 1-little persistence 2-some, 3-a lot of persistence or do not know. Is the compound presistent in the environment? B B=Bioaccumul ate1-3 1-little 2-some, 3-a lot. Does it bioaccumulative in humans or animals or move up the food chain? UC UC=Uncertaint y1-31-little 2-some, 3-a lot. How certain is the information? Total7-30 7-low hazard 30-significant hazards or unknowns, serious concern

56. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07  Community / Social Issues - 12/15  Exposure Issues – 16/20  Hazard / Toxicity – 27/30 Precautionary Assessment Lead

57. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 We have a right to an environment in which we can reach and maintain our potential A matter of POLICY not Risk Assessment Rights and Policy

58. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 “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

59. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Setting goals (Health indicators) Taking preventive action in the face of uncertainty Shifting the burden of responsibility to the proponents of an activity (Who benefits?) Exploring a wide range of alternatives to possibly harmful actions (Is it necessary?) Increasing public participation in decision making (transparency of information & environmental justice) Central components

60. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 The Washington State Public Health Association (WSPHA at www.wspha.org) unanimously adopted two important resolutions at the 13th Annual Washington State Joint Conference on Health that addressed human health and the environment. “Endorsing the Precautionary Principle as a Public Health Tool for Preventing Harm from Persistent Bioaccumulative Toxic Chemicals (PBTs)” Resolved that - “The WSPHA endorses the precautionary principle as a vital component of our preventive approach to public health in Washington State, advancing the goal that all people have an opportunity to reach and maintain their full potential.” WSPHA 2006 Resolutions

61. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 “Supporting Safer Chemicals Policies to Benefit Human and Environmental Health”. This resolution addressed the need to 1) reduce exposure to PBTs, 2) encourages development and use of safer, cost-effective alternative products, materials, and processes, 3) development of ‘green chemistry’, and 4) provide full information on the health effects of all chemicals placed into the marketplace. WSPHA 2006 Resolutions

62. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 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 Precautionary Principle White Paper (www.asmalldoseof.org) Seattle PP working group – CHE-WA Seattle Initiative

63. Beyond Risk Assessment to Precautionary A Small Dose of Toxicology Asthma & Diabetes

64. Beyond Risk Assessment to Precautionary A Small Dose of Toxicology Overweight & Obese

65. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 The Precautionary Principle is part of the evolution in our thinking and decision making toward ensuring human and environmental health. Conclusion

66. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Estimated Costs - National Best Estimate Low EstimateHigh Estimate Lead Poisoning $43.4 Asthma $2.0$0.7$2.3 Cancer $0.3$0.2$0.7 Neurobehavioral Disorders $9.2$4.6 $18.4 TOTAL$54.9$48.8$64.8 Estimated Costs of Pediatric Disease of Environmental Origin, United States,1997 (billions) (From “Environmental Pollutants and Disease in American Children,” Landrigan, Schechter, et.al., 2002)

67. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Estimated Costs - Washington Diseases and disabilities (asthma, cancer, lead exposure, birth defects, and neurobehavioral effects) attributable to environmental contaminants. Best Estimate Direct Costs Indirect Costs Range Childhood$1,875$310.6$1,565 $1,600- $2,200 Adult & child $2,734$782.1$1,953 $2,800- $3,500 Disease/Disability (2004 $ million) Kate Davies Economic costs of diseases and disabilities attributable to environmental contaminants in Washington State. Antioch University Seattle 2005. http://washington.chenw.org/pdfs/EnvironmentalCosts.pdf

68. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Adapted from Kraus and Slovic (1988), Risk Anal., 8: 435. Characteristics of Risk Characteristic Level Examples KnowledgeLittle knownFood additives Much knownAlcoholic drinks NewnessOldGuns NewSpace travel VoluntarinessNot voluntaryCrime VoluntaryRock climbing ControlNot controllableNatural disasters ControllableSmoking DreadednessLittle dreadVaccination Great dreadNerve gas CatastrophicNot likelySunbathing potentialLikelyWar EquityDistributedSkiing UndistributedHazardous dump

69. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07  Food coloring                 Saccharin Microwave ovens Aspirin Anesthetics Power Tools Alcohol Motor vehicles DNA Research Nuclear Power Asbestos Herbicides Pesticides Smoking Dynamite Warfare Handguns Risk Perceptions Catastrophic potential Involuntariness Personal risk Inequity Dread Newness Lack of scientific knowledge Exposure is unknown/unknowable Knowable Unknown Known DreadedLittle Dread

70. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 The Potential of Children

71. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Additional Information  National Research Council, Risk Assessment in the Federal Government: Managing the Process. National Academy Press, Washington, DC, 1983  World Health Organization - The International Programme on Chemical Safety (IPCS) – Risk Assessment – http://www.who.int/pcs/ra_main.html  U.S. Environmental Protection Agencies - National Center for Environmental Assessment (NCEA) – http://cfpub.epa.gov/ncea/  A Small Dose of Toxicology – Risk Assessment - http://www.asmalldoseof.org/toxicology/risk_assessment.php

72. A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Risk Assessment