A Small Dose of Risk Assessment – 2/27/04 An Introduction To Risk Assessment, Risk Management & Precautionary Principle A Small Dose of ™ Risk Assessment DEOHS Summer 511 July 11, 2005 Steven G. Gilbert, PhD, DABT LINKLINK

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Outline  Risk in context of society  Risk Management examples  Principles of risk assessment  Lead Risk – CDC 10 to 2 mcg/cl?  Mercury – cap and trade  Precautionary Principle  Seattle and WA State efforts

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology See: -- smdosesmdose

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology NW Public Health See: nwph Public Health and the Precautionary Principle By Steven G. Gilbert

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology 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 Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Child Health

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Decision Making Risk Assessment and Risk Management in Context of Societal Issues

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Socially Responsibility What is social responsibility? What are our responsibilities to society?

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Socially responsible white guys?

A Small Dose of Risk Assessment – 2/27/04 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 Aldo Leopold

A Small Dose of Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology The Tragedy Cattle Farmers Return on Investment Return for me Not the commons Society suffers

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology No Technical Solutions “It is our considered professional judgment that this dilemma has no technical solution.”

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Problems – Solutions?  Tick-tack-toe  Nuclear disarmament  Bioterrorism  Fish from the sea  Cancer  Lead and kids  Fetal alcohol syndrome  Commons ….

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Toxicology Issues / Solutions?  Cancer (soot & benzene ….)  Radiation exposure  Plant and animal toxins  Pesticides  Drugs  Lead and Mercury  Fetal alcohol syndrome  ….

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Freedom? Restriction of Freedom? Responsibility knowing the problem? What does toxicology say about managing the commons?

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology What is the goal of risk management? “Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential.” Steven G. Gilbert, 1999 Environmental Health

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Examples of Risk Risk Management Examples Alcohol Lead Mercury

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Ethyl Alcohol C H H H OHC H H

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology FAS Child

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Effects of Prenatal Alcohol

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Fetal Alcohol Syndrome (FAS) Researchers at the Univ. of Nantes Early 1970’s FAS – Univ. of Washington 4,000-12,000 infants per year in US 1 to 3 births per 1,000 world wide?? Most common preventable cause of adverse CNS development

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Fetal Alcohol Effect (FAE) Milder form of FAS 7,000-36,000 infants per year in US World wide? Characteristics Growth deficiency Learning dysfunction Nervous systems disabilities

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology  6500 BC. - Lead discovered in Turkey  500 BC-300 AD.- Roman lead smelting produces dangerous emissions (wine)  100 BC. - Greek physicians give clinical description of lead poisoning  2 BC "Lead makes the mind give way.“  1920’s - Lead in gasoline, lead in paint Awareness of Lead

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Lead In Homes

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Lead in Families

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Recycling Lead

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Agency Blood Lead Levels

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Fetal Effects of MeHg

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Life-Long Effects of MeHg

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology The Mercury Cycle

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology 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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Precautionary Principle "When an activity raises threats of harm to the environment or human health, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically." - Wingspread Statement on the Precautionary Principle, Jan. 1998

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Key Words of Toxicology Hazard X Exposure = Risk Individual Susceptibility Dose / Response

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Early Risk Assessment “What is food to one man may be fierce poison to others.” Lucretius (c. 99 B.C.–c. 55 B.C.)

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology "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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology “One death is a tragedy. A million deaths is a statistic.” Joseph Stalin Perspective

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology  1775 – Percivall Pott – Occupational – cancer of scrotum in chimney sweeps  1895 – Bladder cancer in workers in aniline dye industry Historical Awareness

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology  Founding of American Conference of Governmental Industrial Hygienists (ACGIH).  Chemical Substances Committee established to investigate and recommend exposure limits for chemical substances.  Threshold Limit Values (TLVs) for 148 chemicals (exposure limits) Recent Awareness

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Superman

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Risk of What? Obvious Death, Cancer, Acid burn, Birth defect, asthma, Subtle Decreases in learning and memory (lead), Sensitivity of the individual (child)

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Risk Assessment Process of estimating association between an exposure to a chemical or physical agent and the incidence of some adverse outcome.

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Policy developed to deal with hazards identified through risk assessment Process of evaluating alternative regulatory options and selecting among them Risk Management

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Framework for RA and RM Identify hazards Characterize risks Control risks Epidemiology Toxicology In vitro tests Structure/Activity Analysis Potency Exposure Susceptibility Information Regulation Substitution

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Objective of Risk Assessment  Evaluate the risks  Environmental contaminant, drugs, pesticides, industrial chemical  Evaluate uncertainty of data  Set target levels of exposure  Food, air, water, work place  Provide information to agencies  Regulatory agencies, Manufacturers, Environmental/Consumer Agencies

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Steps in Risk Assessment  Hazard Identification  Exposure Assessment  Dose-Response Assessment  Risk Characterization

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Hazard Identification Review human and animal data to determine if a chemical or agent has biological effects

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Hazard Identification  Research  Structure-Activity Analysis  Short-term Screening Tests  Animal Bioassays  Human Epidemiological Data

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Structure-Activity Analysis Does structure resemble that of a known toxic agent? Computer modeling

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Short-term Screening Tests Cell Culture, Tissue Culture Does the chemical or agent adversely effects cells?

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Animal Bioassays Animal Studies Does the chemical or agent causes effect animals? What is the potentially for human toxicity?

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology 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 Risk Assessment – 2/27/04 A Small Dose of Toxicology Pros and Cons - Animals Advantages  Monitor progress of toxicity/carcinogenicity  Can directly link with exposure  Can be used to predict human risks Disadvantages  Can be very expensive (>$1 M)  Can take many years

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Human Epidemiological Human Studies Does the chemical or agent causes adverse effect in human populations?

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology 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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology 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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Examples of Variability Children spend more time on floor – more hand to mouth behavior than adults Occupation – exposure to other chemicals Rate of breathing higher in children than adults 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.

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology 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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Exposure Assessment  Route of exposure (skin, oral, inhalation)  Amount of exposure (dose)  Duration of exposure  To whom (animals, humans, environment)

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Home environment Current events Workplace School Government Decisions (war) Global and local environment Exposure Issues

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Dose-Response Assessment How much exposure to a chemical or agent will cause what effect?

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Chemical Potency Dose Response Threshold (NOAEL ED50

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Hazard (including sensitive populations) –May require low dose extrapolation Exposure –Route of exposure, amount, duration dermal, oral, inhalation, injection Risk Characterization Risk = Hazard X Exposure

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology  Uncertainty  Perception  Comparison  Education  Regulation Risk Management

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology How do you know? How good is the data? Uncertainty

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology 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 Risk Assessment – 2/27/04 A Small Dose of Toxicology Use of Uncertainty Factors Animal Dose Response Data NOAEL (No Observed Adverse Effect Level) 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)

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Reducing Uncertainty Upstanding mechanism of action Physiologically based pharmacokinetic models (distribution and metabolism) Sample size

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Comparing Risks  By probability  By expected value  By outrage  By exposure  By experts

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Annual Risk Of Death In The U.S. HAZARDRISK PER MILLION All causes9,000.0 Motor vehicle accidents210.0 Work accidents150.0 Homicides93.0 Drowning37.0 Poisoning, Solids/liquids17.0 Railroads0.9 Civil aviation0.8 Bits and stings0.2 “TO LIVE, IS TO RISK DYING”

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology 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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology  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  Lead Unknown Known DreadedLittle Dread

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Adapted from Slovic et al. (1979), Environ., 21: 14. Differences in Risk Perception Activity/Agent Rank by Risk Analyst Rank by non- Risk Analyst Motor Vehicles12 Smoking24 Alcohol36 Handguns43 Surgery510 Motorcycles65 X-rays722 Pesticides89 Electric Power918 Swimming1019 Nuclear Power201

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Case Study LEAD

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology "Lead makes the mind give way." Ancient Awareness Greek Dioscerides - 2nd BC

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Agency Blood Lead Levels

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology “Conclusions: Blood lead concentrations, even those below 10 mgc/dL, are inversely associated with children’s IQ scores at three and five years of age, and associated declines in IQ are greater at these concentrations than at higher concentrations. These findings suggest that more U.S. children may be adversely affected by environmental lead than previously estimated.” Canfield et al. 2003, NEJM, 384 Canfield et al…, 2003

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology 25 DAYS -- BLOOD 40 DAYS -- SOFT TISSUE 20 YEARS -- BONE Half-life Of Lead

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Lead - Absorption ORALLY CONSUMED LEAD ABSORBED CHILDREN – 30-50% OF LEAD ADULTS – 5-10% OF LEAD Increased During Pregnancy

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Needleman, NEJM, 1979

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Lead Based Paint US medical authorities diagnose childhood lead poisoning Child lead poisoning linked to lead-based paints France, Belgium and Austria ban white-lead interior paint Pediatric lead-paint poisoning death from eating crib paint is described National Lead Company admits lead is a poison League of Nations bans white-lead interior paint; US declines to adopt Report concludes eating lead paint chips causes physical and neurological disorders, behavior, learning and intelligence problems in children Lead-Based Paint Poisoning Prevention Act passed

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Lead Industry Advertisements History of Lead Industry Advertisements (LINK)LINK

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Lead-associated Reading Deficits in U.S. Children Blood lead levels (  g/dl) Reading Score Lanphear BP, et al. Public Health Reports 2000;115: (BL’s slide)

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Canfield R, et al. NEJM 2003;348: IQ and Blood Lead Life time overall Increase in 1 mcg/dl = 0.87 IQ drop Covariates - 1 mcg/dl = 0.46 IQ drop 1 to 10 mcg/dl (bigger drop) Increase in 1 mcg/dl = 1.37 IQ drop Non-linear - 1 mcg/dl = 7.4 IQ drop

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Societal Consequences (Curtsey Bernard Weiss)

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Environmental Pollutants and Disease in American Children: Estimates of Morbidity, and Costs for Lead Poisoning, Asthma, Cancer, and Developmental Disabilities, by Landrigan, P. et al. EHP, 110, July 2002, Cost of Childhood Lead Assumptions in calculating costs All lead is harmful and from environment Blood lead of children age 5 – 2.7 ug/dl (CDC) 5-year old boys (1,960,200) and girls (1,869,800) 1 ug/dl of lead = 0.25 IQ point reduction Cost – boys $27.8 and girls $15.6 Billion Total Costs $43.4 Billion

A Small Dose of Risk Assessment – 2/27/04 Current CDC Policy Blood lead level µg/dL) b Actions Time frame for beginning intervention 10-14Provide caregiver lead education. Provide follow-up testing. Refer the child for social services if necessary. Within 30 days 15-19Above actions, plus: If BLLs persist (i.e., 2 venous BLLs in this range at least 3 months apart) or increase, proceed according to actions for BLLs Within 2 weeks 20-44Above actions, plus: Provide coordination of care (case management). Provide clinical evaluation and care. c Provide environmental investigation and control current lead hazards. Within 1 week 45-70Above actions.Within 48 hours 70 or higherAbove actions, plus hospitalize child for chelation therapy immediately. Within 24 hours

A Small Dose of Risk Assessment – 2/27/04 Proposed CDC Policy Blood lead level (µg/dL) ActionsTime frame for beginning intervention <2No action 2-5Provide caregiver lead education. Provide follow-up testing. Refer the child for social services to investigate possible sources of lead exposure. Within 30 days 5-10Above actions, plus:If BLLs persist (i.e., 2 venous BLLs in this range at least 3 months apart) or increase, proceed according to actions for BLLs Within 2 weeks 10-20Above actions, plus: Provide coordination of care (case management). Provide clinical evaluation and care. Provide environmental investigation and control current lead hazards. Within 1 week 20-70Above actions.Within 24 hours 70 or higherAbove actions, plus hospitalize child for chelation therapy immediately. Within 24 hours

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Recycling Lead

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Case Study Mercury

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Hg – Like Water

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Hg – Solid Enough to Sit On

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Outbreaks of MeHg Poisoning PlaceYearCases Minamata Nigata Guatemala Ghana Pakistan Iraq Iraq19601,002 Iraq197140,000 On-going2001???

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Iraq Infant - Effects of Mercury

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Inorganic - elemental mercury vapor Hg 0 Biotransformation Organic - Methylmercury - CH 3 Hg + Bioaccumulatio n Mercury to Methyl Mercury

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Mercury Release 50-75% mercury of released in the environment related to human activities

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Atmospheric Hg

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Ambient Water Sediments Edible Fish Inorganic Mercury Methyl- Mercury In Humans Biomethylation Bioaccumulation Exposure Discharge Biotransformation of Mercury

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Blindness - Deafness Cerebral Palsy - Seizures Abnormal reflexes & muscle tone Retarded motor development Visual and Auditory Deficits Delayed motor development Altered DRH performance Neurobehavioral Effects

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Decrease in Brain Size Cell loss Disorganization of cells Cell migration failures Effects On The Brain

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology  MONKEY - 25 µg/kg - LOAEL  RAT - 10 µg/kg - LOAEL  RAT - 50 µg/kg - replicated Animal - Risk Assessment

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology  2.5 µg/kg - NOAEL (animals)  0.25 µg/kg - Human  µg/kg - Sensitive populations Animal - Risk Assessment (the rule of dividing by 10)

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology ppm hair - LOAEL ppb blood - LOAEL µg/kg 0.06 µg/kg - RfD Human - Risk Assessment

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Mercury Fishing Advisories  In 2000, 41 States have over 2000 fish consumption advisories  An increase form 27 in 1993  Pregnant women, nursing mothers, women who intend to have children, and children under 15

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Reduce environmental release Restrict global production and sale Advise women of child bearing age Research mechanisms of action Assess neurodegenerative effects Recommendations

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology MeHg Consumption Limits US EPA – 0.1 ug/kg-day US FDA – 1 ppm (mg/kg) in tuna

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Mercury A Global Issue Mercury distribution and exposure is a global problem

A Small Dose of Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology PBDEs in House Dust (ppb) From EWG - Toxic Fire Retardants Contaminate American Homes -

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology PBDEs in Breast Milk (ppb) From EWG - Toxic Fire Retardants in Breast Milk from American Mothers -

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Developmental Data 2863 above 1 Million pounds 78.2% no data 21.4% some data 12 or 0.4% good data

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology  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

A Small Dose of Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology The challenge “the knowledge of how to use knowledge for the social good” Knowledgeable Bioethics

A Small Dose of Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 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, Precautionary Principle

A Small Dose of Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 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 (environmental justice) Wingspread Conference, Central components

A Small Dose of Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 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 PP working group Seattle Initiative

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Seattle Precautionary Principle White Paper ( Inclusion of PP in Comp Plan Environment Element ( ehensive_Plan/DPD_ asp) LinkLink Result of Effort

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology “Protecting Public Health by Adopting the Precautionary Principle as an Approach to Decision Making” Resolution Submitted to Washington State Public Health Association WSPHA Resolution

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology The citizen toxicologist is a thoughtful advocate for human and environmental health, who strives to share their scientific knowledge with the public, speaking to public interests rather than private or special interests. Citizen Toxicologist Socially Responsible Toxicologist

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Testifying Writing review papers K-12 class room teaching Adding expertise to community groups Education Mentoring Speakers Bureau Socially Responsible Actions

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Forum in which to discuss the ethical implications of results from our science as well as the resulting legal and social implications SOT meeting – workshop on Conflict of Interest SOT - ELSI Specialty Section

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology 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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology The Potential of Children

A Small Dose of Risk Assessment – 2/27/04 Additional Information  The Science and Environmental Health Network (SEHN) (  Late lessons from early warnings: the precautionary principle – 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

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology A Small Dose of ™ Risk Assessment

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Additional Information  Web Sites  World Health Organization - The International Programme on Chemical Safety (IPCS) – Risk Assessment –  U.S. Environmental Protection Agencies - National Center for Environmental Assessment (NCEA) – Access:

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Authorship Information For Additional Information Contact Steven G. Gilbert, PhD, DABT Web: This presentation is supplement to “A Small Dose of Toxicology”

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Precautionary Principle "When an activity raises threats of harm to the environment or human health, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically." - Wingspread Statement on the Precautionary Principle, Jan. 1998

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Scientific Process Variability Uncertainty

A Small Dose of Risk Assessment – 2/27/04 A Small Dose of Toxicology Statistical Model Fundamental Types of Uncertainty

A Small Dose of Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 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

A Small Dose of Risk Assessment – 2/27/04 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