April 4, 2019 A Small Dose of Toxicology - Overview

Precautionary Assessment April 4, 2019 Precautionary Assessment “Precautionary Assessment"-- a community approach to risk assessment (Critical Analysis of Risk Assessment & Alternative Approaches) Northwest Toxic Communities Coalition April 5,, 2009 Steven G. Gilbert, PhD, DABT www.asmalldoseof.org www.toxipedia.org A Small Dose of Toxicology - Overview

April 4, 2019 Doubt Is Their Product How Industry’s Assault on Science Threatens Your Health” David Michaels 2008 - Oxford A Small Dose of Toxicology - Overview

A Small Dose of Toxicology April 4, 2019 A Small Dose of Toxicology See: www.asmalldoseof.org -- smdose A Small Dose of Toxicology - Overview

Small Dose of Toxicology April 4, 2019 Small Dose of Toxicology A Small Dose of Toxicology - Overview

Milestones of Toxicology April 4, 2019 Milestones of Toxicology A Small Dose of Toxicology - Overview

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. Toxipedia

www.ipmopedia.org

Coupling art and science to forge a more healthy and peaceful world Healthy World Theater Coupling art and science to forge a more healthy and peaceful world 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. www.healthyworldtheater.org

World Library of Toxicology – www.wltox.org

LDDI Consensus Statement April 4, 2019 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 A Small Dose of Toxicology - Overview

Child Health

So Many Chemicals so Little Data April 4, 2019 So Many Chemicals so Little Data 2863 above 1 Million pounds 12 or 0.4% good data 21.4% some data 78.2% no data www.preventingharm.org A Small Dose of Toxicology - Overview

April 4, 2019 The Consequences 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 A Small Dose of Toxicology - Overview

April 4, 2019 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.) A Small Dose of Toxicology - Overview

April 4, 2019 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. A Small Dose of Toxicology - Overview

Risk Assessment – Arbitrary and Capricious April 4, 2019 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 A Small Dose of Toxicology - Overview

Vision for Child Health April 4, 2019 Vision for Child Health “Children can develop and mature in an environment that allows them to reach and maintain their full potential.” A Small Dose of Toxicology - Overview

Human & Environmental Health April 4, 2019 Human & Environmental Health “Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential.” S. Gilbert (1999) A Small Dose of Toxicology - Overview

Socially responsible white guys? April 4, 2019 Socially responsible white guys? A Small Dose of Toxicology - Overview

Aldo Leopold The First Bioethicist April 4, 2019 The First Bioethicist Aldo Leopold "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 ---------- 1887 - 1948 ---------- A Small Dose of Toxicology - Overview

April 4, 2019 Limits on Freedom “An ethic, ecologically, is a limitation on freedom of action in the struggle for existence” Aldo Leopold A Small Dose of Toxicology - Overview

“The Commons” The Tragedy of the Commons April 4, 2019 “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968 A Small Dose of Toxicology - Overview

The Tragedy of the Commons By Garrett Hardin, Science, 1968 April 4, 2019 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 A Small Dose of Toxicology - Overview

Problems – Solutions? Lead and kids Fetal alcohol syndrome April 4, 2019 Problems – Solutions? Lead and kids Fetal alcohol syndrome Nuclear disarmament Bioterrorism Ocean Fisheries Persistent chemicals The Commons Another point that Hardin made was that many problems do not have a technical solution – these can range from Tick-tack-toe to disarmament to managing fish stocks and to many of the issues that our panelist will briefly discuss. A Small Dose of Toxicology - Overview

Sir Austin Bradford Hill April 4, 2019 Sir Austin Bradford Hill "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) A Small Dose of Toxicology - Overview

Determining Causation April 4, 2019 Determining Causation Strength of association Consistency of findings Biological gradient Temporal sequence Biologic or theoretical plausibility Coherence with established knowledge Specificity of association Sir Austin Bradford Hill (1965) A Small Dose of Toxicology - Overview

Precautionary Principle April 4, 2019 Precautionary Principle “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. A Small Dose of Toxicology - Overview

Central components Setting goals (Health indicators) April 4, 2019 Central components 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) A Small Dose of Toxicology - Overview

Key Words of Toxicology April 4, 2019 Key Words of Toxicology Dose / Response Hazard X Exposure = Risk Individual Susceptibility A Small Dose of Toxicology - Overview

Modern Risk Assessment April 4, 2019 Modern Risk Assessment Developed in 1960-1970s Concern over increased cancer rates Expanded to non-cancer effects A Small Dose of Toxicology - Overview

April 4, 2019 Perspective "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 A Small Dose of Toxicology - Overview

Quantitative Risk Assessment April 4, 2019 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 A Small Dose of Toxicology - Overview

Steps in Risk Assessment April 4, 2019 Steps in Risk Assessment Hazard Identification Exposure Assessment Dose-Response Assessment Risk Characterization A Small Dose of Toxicology - Overview

What Hazard? Obvious Subtle April 4, 2019 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) A Small Dose of Toxicology - Overview

Hazard Identification April 4, 2019 Hazard Identification Review human and animal data to determine if a chemical or agent has biological effects. A Small Dose of Toxicology - Overview

Toxicity Endpoints Carcinogenicity Mutations Altered immune function April 4, 2019 Toxicity Endpoints Carcinogenicity Mutations Altered immune function Teratogenicity Altered reproductive function Neuro-behavioral toxicity Organ-specific effects Ecological effects (wildlife, environmental persistence) A Small Dose of Toxicology - Overview

Exposure Assessment Route of exposure (skin, oral, inhalation) April 4, 2019 Exposure Assessment Route of exposure (skin, oral, inhalation) Amount of exposure (dose) Duration of exposure To whom (animals, humans, environment) Children, other sensitive individuals A Small Dose of Toxicology - Overview

Exposure Issues Home environment Workplace (occupational) School Food April 4, 2019 Exposure Issues Home environment Workplace (occupational) School Food Consumer products Global and local environment A Small Dose of Toxicology - Overview

Dose-Response Assessment April 4, 2019 Dose-Response Assessment How much exposure to a chemical or agent will cause what effect? Dose – Response A Small Dose of Toxicology - Overview

Some Jargon LOAEL – Lowest Observed Adverse Effect Level (mg/kg) April 4, 2019 Some Jargon LOAEL – Lowest Observed Adverse Effect Level (mg/kg) NOAEL – No Observed Adverse Effect Level (mg/kg) RfD – Reference Dose (mg/kg-day) A Small Dose of Toxicology - Overview

Greater Dose – Greater Response April 4, 2019 Greater Dose – Greater Response Response ED50 Threshold (NOAEL) LOAEL Dose A Small Dose of Toxicology - Overview

Risk Characterization April 4, 2019 Risk Characterization Risk = Hazard X Exposure Hazard (including sensitive populations) Low dose extrapolation Exposure Route of exposure, amount, duration dermal, oral, inhalation, injection To Whom? Sensitive Individuals? A Small Dose of Toxicology - Overview

Use of Uncertainty Factors April 4, 2019 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 A Small Dose of Toxicology - Overview

Human Subject Variability April 4, 2019 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 A Small Dose of Toxicology - Overview

April 4, 2019 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) A Small Dose of Toxicology - Overview

Use of Uncertainty Factors April 4, 2019 Use of Uncertainty Factors Animal Dose Response Data NOAEL (No Observed Adverse Effect Level) or LOAEL Divide by 10 (Account for inadequate animal data) (Animal to Human Extrapolation) (Human Variability or Individual Sensitivity) Reference Dose (RfD) Or Acceptable Daily Intake (ADI) A Small Dose of Toxicology - Overview

What Is This? O CH3 CH3 N N O N N CH3 7 1 3 April 4, 2019 Caffeine – 1,3,7-trimethylxanthine N CH3 A Small Dose of Toxicology - Overview

Mercury & Toxicology

April 4, 2019 The Mercury Cycle A Small Dose of Toxicology - Overview

April 4, 2019 Atmospheric Hg A Small Dose of Toxicology - Overview

Neurobehavioral Effects Blindness - Deafness Cerebral Palsy - Seizures Abnormal reflexes & muscle tone Retarded motor development Visual and Auditory Deficits Delayed motor development Human and animal data

Effects On The Brain Decrease in Brain Size Cell loss Disorganization of cells Cell migration failures Behavioral effects – learning and memory

Fetal Effects of MeHg

Animal - Risk Assessment MONKEY - 25 µg/kg - LOAEL RAT - 10 µg/kg - LOAEL RAT - 50 µg/kg - replicated

Animal - Risk Assessment 2.5 µg/kg - NOAEL (animals) 0.25 µg/kg - Human 0.025 µg/kg - Sensitive populations (the rule of dividing by 10)

Human - Risk Assessment • 10-20 ppm hair - LOAEL • • 40-80 ppb blood - LOAEL • • 0.645 µg/kg • • 0.06 µg/kg - RfD • Gilbert, S.G., and Grant-Webster, K.S. Neurobehavioral effects of developmental methylmercury exposure. Env. Health Persep. 103(Suppl 6), 135-142, 1995.

MeHg Consumption Limits US EPA – 0.1 ug/kg-day US FDA – 1 ppm (mg/kg) in tuna

"Lead makes the mind give way." Ancient Awareness "Lead makes the mind give way." Greek Dioscerides - 2nd BC

Agency Blood Lead Levels

Recycling Lead

Limitations of Risk Assessment April 4, 2019 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?? A Small Dose of Toxicology - Overview

Precautionary Assessment April 4, 2019 Precautionary Assessment An approach to evaluating the scientific, safety, community, ethical, and social issues related to a compound or procedure. Community / Social Issues Exposure Issues Hazard / Toxicity A Small Dose of Toxicology - Overview

Precautionary Assessment April 4, 2019 Precautionary Assessment Community / Social Issues G = Goal N = Need F = Future Generations D = Democratic, community based process A = Alternatives A Small Dose of Toxicology - Overview

Precautionary Assessment April 4, 2019 Precautionary Assessment Initial Parameter Score Comment   Community / Social Issues Evaluate effects on the community and related social issues. G G=Goal 1-3 1-a lot, 2-some, 3-little. Does this move forward the goal of human and environmental health? N N=Need 1-a lot, 2-some, 3-little or not sure. Ask the question: Is it necessary? Do we really need this? F F=Future Generations 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 process 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. A A=Alternatives 1-alternatives were carefully considered, 2-some consideration, 3-no consideration. Where alternatives considered? Total 5-15 5-good, supportive of health and community 15-poor, not supportive of health or community A Small Dose of Toxicology - Overview

Precautionary Assessment April 4, 2019 Precautionary Assessment Exposure Issues E = Exposure M = Multiple exposures Ch = Children exposed CP = Consumer products O = Occupational exposure F = Food exposure A Small Dose of Toxicology - Overview

Precautionary Assessment April 4, 2019 Precautionary Assessment   Exposure Issues Evaluate potential exposure issues. E E=Exposure 0-3 0-none, 1-little, 2-some, 3-high. Do we have control over the exposure? M M=Multiple exposures 0-none, 1-little, 2-some, 3-high. Is there exposure to other chemicals with similar hazard? Ch Ch=Children exposed 0,3,5 0-none, 3-little, 5-some or high or don't know. Children are often more vulnerable. Are children being exposed. CP CP=Consumer products 0-not in consumer products, 1-little, 2-some, 3- a lot or do not know. Is this compound in consumer products? O O=Occupational exposure 0-no occupational exposure, 1-little, 2-some, 3- a lot or do not know. Is there occupational exposure? F F=Food exposure 0-not in food supply, 1-little, 2-some, 3- a lot or do not know. Is the compound present in the food supply. Total 0-20 0-no exposure, no problems 20-significant exposure, serious concern A Small Dose of Toxicology - Overview

Precautionary Assessment April 4, 2019 Precautionary Assessment Hazard / Toxicity H = Hazard IS = Individual Sensitivity EC = Ecological hazard UC = Uncertainty V = Volume P = Persistent A Small Dose of Toxicology - Overview

Precautionary Assessment April 4, 2019 Precautionary Assessment   Hazard / Toxicity Evaluate potential hazards. H H=Hazard 1,5,10 1-low, 5-some, 10-high. Follow classical hazard evaluation, pick endpoint, exam relevant quality studies (cancer, reproductive, neurotoxicity, irreversible) IS IS=Individual Sensitivity 1-3 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 hazard 1-little 2-some, 3-a lot. Is it a hazard to other species or the environment? V V=Volume 1-5 how much is produced (1=research only, 2=<1000 lbs, 3=<10,000, 4=<100,000, 5=>100,000 or do not know) P P=Persistent 1-little persistence 2-some, 3-a lot of persistence or do not know. Is the compound presistent in the environment? B B=Bioaccumulate 1-little 2-some, 3-a lot. Does it bioaccumulative in humans or animals or move up the food chain? UC UC=Uncertainty 1-little 2-some, 3-a lot. How certain is the information? Total 7-30 7-low hazard 30-significant hazards or unknowns, serious concern A Small Dose of Toxicology - Overview

Precautionary Assessment April 4, 2019 Precautionary Assessment Lead Community / Social Issues - 12/15 Exposure Issues – 16/20 Hazard / Toxicity – 27/30 A Small Dose of Toxicology - Overview

April 4, 2019 Rights and Policy We have a right to an environment in which we can reach and maintain our potential A matter of POLICY not Risk Assessment A Small Dose of Toxicology - Overview

Precautionary Principle April 4, 2019 Precautionary Principle “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. A Small Dose of Toxicology - Overview

Central components Setting goals (Health indicators) April 4, 2019 Central components 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) A Small Dose of Toxicology - Overview

April 4, 2019 WSPHA 2006 Resolutions 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.” A Small Dose of Toxicology - Overview

April 4, 2019 WSPHA 2006 Resolutions “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. A Small Dose of Toxicology - Overview

WSPHA 2008 Resolutions Submittal: October 2008 Annual Meeting April 4, 2019 WSPHA 2008 Resolutions 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 A Small Dose of Toxicology - Overview

Seattle PP working group – CHE-WA April 4, 2019 Seattle Initiative 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 A Small Dose of Toxicology - Overview

April 4, 2019 Conclusion The Precautionary Principle is part of the evolution in our thinking and decision making toward ensuring human and environmental health. A Small Dose of Toxicology - Overview

The Potential of Children April 4, 2019 The Potential of Children A Small Dose of Toxicology - Overview

Additional Information April 4, 2019 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 A Small Dose of Toxicology - Overview

April 4, 2019 Risk Assessment A Small Dose of Toxicology - Overview

Characteristics of Risk April 4, 2019 Characteristics of Risk Characteristic Level Examples Knowledge Little known Food additives Much known Alcoholic drinks Newness Old Guns New Space travel Voluntariness Not voluntary Crime Voluntary Rock climbing Control Not controllable Natural disasters Controllable Smoking Dreadedness Little dread Vaccination Great dread Nerve gas Catastrophic Not likely Sunbathing potential Likely War Equity Distributed Skiing Undistributed Hazardous dump Adapted from Kraus and Slovic (1988), Risk Anal., 8: 435. A Small Dose of Toxicology - Overview

Overweight & Obese April 4, 2019 A Small Dose of Toxicology - Overview

Risk Perceptions Unknown w w Knowable w w w w w w w Dread Little Dread April 4, 2019 Risk Perceptions Unknown w Food coloring w DNA Research Knowable w w Saccharin Nuclear Power Newness Lack of scientific knowledge Exposure is unknown/unknowable Microwave ovens w w Asbestos w Aspirin Herbicides w Pesticides w Dread Little Dread Dreaded Catastrophic potential Involuntariness Personal risk Inequity w Anesthetics w Power Tools w Smoking w w Dynamite Alcohol w w Warfare Motor vehicles w Handguns Known A Small Dose of Toxicology - Overview

Estimated Costs - National April 4, 2019 Estimated Costs - National Estimated Costs of Pediatric Disease of Environmental Origin, United States,1997 (billions) Best Estimate Low Estimate High Estimate Lead Poisoning   $43.4 Asthma  $2.0 $0.7 $2.3 Cancer  $0.3 $0.2 Neurobehavioral Disorders $9.2 $4.6 $18.4 TOTAL $54.9 $48.8 $64.8 (From “Environmental Pollutants and Disease in American Children,” Landrigan, Schechter, et.al., 2002) A Small Dose of Toxicology - Overview

Estimated Costs - Washington April 4, 2019 Estimated Costs - Washington Diseases and disabilities (asthma, cancer, lead exposure, birth defects, and neurobehavioral effects) attributable to environmental contaminants. Disease/Disability (2004 $ million) 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 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 A Small Dose of Toxicology - Overview

Asthma & Diabetes April 4, 2019 A Small Dose of Toxicology - Overview