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Beyond Risk Assessment to Precautionary A Small Dose of Toxicology
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Beyond Risk Assessment to Precautionary A Small Dose of Toxicology Precautionary Assessment Steven G. Gilbert, PhD, DABT www.asmalldoseof.org www.toxipedia.org “Precautionary Assessment"-- a community approach to risk assessment (Critical Analysis of Risk Assessment & Alternative Approaches) Northwest Toxic Communities Coalition April 5,, 2009
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Doubt Is Their Product David Michaels 2008 - Oxford How Industry’s Assault on Science Threatens Your Health”
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 A Small Dose of Toxicology See: www.asmalldoseof.org -- smdosesmdose
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Small Dose of Toxicology
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Milestones of Toxicology
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 www.toxipedia.org A free toxicology encyclopedia and resource center that anyone can edit. Toxipedia provides comprehensive, accurate, and scientifically based information on the hazards and risks of chemical and physical agents, with the goal of advancing human and environmental health. ToxipediaToxipedia
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 www.ipmopedia.org
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Healthy World Theater Healthy World Theater reaches to the heart to promote awareness and understanding through the arts to create a more healthy and peaceful world so that all creatures may reach, maintain, and enjoy their potential. Coupling art and science to forge a more healthy and peaceful world www.healthyworldtheater.org
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 World Library of Toxicology – www.wltox.org
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 LDDI Consensus Statement Scientific Consensus Statement on Environmental Agents Associated with Neurodevelopmental Disorders Developed by the Collaborative on Health and the Environment’s Learning and Developmental Disabilities Initiative November 7, 2007 http://www.iceh.org/LDDI.html
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Child Health
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 So Many Chemicals so Little Data 2863 above 1 Million pounds 78.2% no data 21.4% some data 12 or 0.4% good data www.preventingharm.org
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Nearly 12 million children (17%) under age 18 in the US suffer from one or more developmental disabilities Learning disabilities – 5-10% of kids in public school ADHD – 3-6% of all school kids, maybe higher The Consequences
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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.)
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Risk Assessment Philip Handler said about balancing risks and benefits: “A sensible guide would surely be to reduce exposure to hazard whenever possible, to accept substantial hazard only for great benefit, minor hazard for modest benefit, and no hazard at all when the benefit seems relatively trivial.” (Handler, 1979). Handler P. 1979. Some comments on risk. In: The National Research Council in 1979; Current Issues and Studies. Washington, DC: National Academy of Sciences, 3-24.
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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
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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
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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
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Socially responsible white guys?
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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)
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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.
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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)
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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
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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
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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
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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)
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Greater Dose – Greater Response Dose Response Threshold (NOAEL) ED50 LOAEL
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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
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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
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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
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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)
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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)
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 What Is This? N N N N CH 3 O O 1 3 7
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Mercury & Toxicology
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 The Mercury Cycle
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Atmospheric Hg
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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
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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
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Fetal Effects of MeHg
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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
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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)
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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.
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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
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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
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Agency Blood Lead Levels
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Recycling Lead
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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??
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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.
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Submittal: October 2008 Annual Meeting Title: Supporting Actions to Reduce Exposures to Lead to Benefit Children’s Health, Learning and Futures RESOLVED, THAT: WSPHA supports a reduction of the CDC blood lead level guidelines for action from 10 μg/dL to 2 μg/dL as a crucial step toward achieving a goal that no child in Washington State hasa blood lead level above 2 μg/dL WSPHA 2008 Resolutions
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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
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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
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 The Potential of Children
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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
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A Small Dose of Toxicology Beyond Risk Assessment to Prec – 09/19/07 Risk Assessment
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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
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Beyond Risk Assessment to Precautionary A Small Dose of Toxicology Overweight & Obese
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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
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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)
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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
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Beyond Risk Assessment to Precautionary A Small Dose of Toxicology Asthma & Diabetes
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