risk assessment – 12/05/06 a small dose of toxicology risk assessment and risk communication...
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Risk Assessment – 12/05/06 A Small Dose of Toxicology
Risk Assessment and Risk Communication
Steven G. Gilbert, PhD, DABT
www.asmalldoseof.orgwww.toxipedia.org
How Chemicals Affect Your HealthDecember 5, 2006
A Small Dose of Toxicology
A Small Dose of Toxicology Risk Assessment – 12/05/06
Benefits & Risk
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Child Health
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Outline
Risk Assessment – Arbitrary and Capricious??
Ethics and Risk Principles of Risk Assessment Risk Assessment - examples Weaknesses of Risk Assessment
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• Vision of Child Health
• Knowledge of Reproductive and Developmental Toxicology
• Policy Approach within an ethical framework• Social responsibilities• No technical solutions• Restriction of freedoms• Precautionary Principle
Convergence of Issues
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“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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“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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Socially responsible white guys?
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"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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“An ethic, ecologically, is a limitation on freedom of action in the struggle for
existence”Aldo Leopold
Limits on Freedom
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“The Commons”
The Tragedy of the CommonsBy Garrett Hardin, Science, 1968
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Technical Solutions
“It is our considered professional judgment that
this dilemma has no technical solution.”
The Tragedy of the CommonsBy Garrett Hardin, Science, 1968
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Problems – Solutions?
Lead and kids Fetal alcohol syndrome Nuclear disarmament Bioterrorism Ocean Fisheries Persistent chemicals The Commons
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"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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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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“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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• 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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Key Words of Toxicology
Hazard X Exposure = Risk
Individual Susceptibility
Dose / Response
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Early Risk Assessment
“What is food to one man may be fierce poison to others.”
Lucretius (c. 99 B.C.–c. 55 B.C.)
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"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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Developed in 1960-1970s Concern over increased cancer ratesExpanded to non-cancer effects
Modern Risk Assessment
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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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Steps in Risk Assessment
Hazard IdentificationExposure AssessmentDose-Response AssessmentRisk Characterization
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What Hazard?
ObviousDeath, Cancer, Acid burn, Birth defect, asthma …..
SubtleDecreases in learning and memory (lead)
Loss of potential
Sensitivity of the individual (child)
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Hazard Identification
Review human and animal data to determine if a chemical or agent has biological effects.
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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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Exposure Assessment
Route of exposure (skin, oral, inhalation)
Amount of exposure (dose)Duration of exposureTo whom (animals, humans,
environment) Children, other sensitive individuals
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• Home environment• Workplace (occupational)• School• Food• Consumer products• Global and local environment
Exposure Issues
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Dose-Response Assessment
How much exposure to a chemical or agent will cause what effect?
Dose – Response
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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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Greater Dose – Greater Response
Dose
Res
po
nse
Threshold (NOAEL)
ED50
LOAEL
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Hazard (including sensitive populations)
–Low dose extrapolationExposure
– Route of exposure, amount, duration• dermal, oral, inhalation, injection
– To Whom? Sensitive Individuals?
Risk Characterization
Risk = Hazard X Exposure
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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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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
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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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Examples of Variability
• Children spend more time on floor – more hand to mouth behavior than adults
• Rate of breathing higher in children than adults
• Occupation – exposure to other chemicals• Lung function and susceptibility are altered
by smoking or asthma• Disease effects liver function
The overall dose-response behavior is subject to both intra-individual and inter-individual
variability.
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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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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)
A Small Dose of Toxicology Risk Assessment – 12/05/06Superman
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Mercury & Toxicology
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The Mercury Cycle
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Atmospheric Hg
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• 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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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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Fetal Effects of MeHg
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MONKEY - 25 µg/kg - LOAELRAT - 10 µg/kg - LOAELRAT - 50 µg/kg - replicated
Animal - Risk Assessment
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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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• 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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MeHg Consumption Limits
US EPA – 0.1 ug/kg-day
US FDA – 1 ppm (mg/kg) in tuna
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"Lead makes the mind give way."
Ancient Awareness
GreekDioscerides - 2nd BC
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Agency Blood Lead Levels
60
40
3025
2015
10
20
10
20
30
40
50
60
Blo
od
Lea
d (
ug
/dl)
CDC1960
CDC1973
CDC1975
CDC1985
WHO1986
EPA1986
CDC1990
CDC2006?
Agency and Year
Acceptable Childhood Blood Lead Levels
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Recycling Lead
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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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Developmental 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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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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Estimated Costs - National
Best Estimate
Low Estimate High Estimate
Lead Poisoning $43.4 $43.4 $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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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
A Small Dose of Toxicology Risk Assessment – 12/05/06Adapted from Kraus and Slovic (1988), Risk Anal., 8: 435.
Characteristics of RiskCharacteristic Level Examples
Knowledge Little known Food additivesMuch known Alcoholic drinks
Newness Old GunsNew Space travel
Voluntariness Not voluntary CrimeVoluntary Rock climbing
Control Not controllable Natural disastersControllable Smoking
Dreadedness Little dread VaccinationGreat dread Nerve gas
Catastrophic Not likely Sunbathingpotential Likely WarEquity Distributed Skiing
Undistributed Hazardous dump
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Food coloring
Saccharin
Microwave ovens
Aspirin
Anesthetics
Power Tools
Alcohol
Motor vehicles
DNA Research
Nuclear Power
Asbestos
HerbicidesPesticides
Smoking
Dynamite
Warfare
Handguns
Risk Perceptions
Catastrophic potentialInvoluntariness
Personal riskInequity
Dread
NewnessLack of scientific knowledge
Exposure is unknown/unknowable
Knowable
Unknown
Known
DreadedLittle Dread
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The Potential of Children
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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 Risk Assessment – 12/05/06
Risk Assessment