Precautionary Assessment

Beyond Risk Assessment to Precautionary A Small Dose of Toxicology


Precautionary Assessment

Steven G. Gilbert, PhD, DABT

www.asmalldoseof.orgwww.toxipedia.org

Getting Out of the Risk Assessment Box: Precautionary Approaches for Public Health

(Critical Analysis of Risk Assessment & Alternative Approaches)

How Chemicals Affect Your Health

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.)


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.


Outline

Risk Assessment – Arbitrary and Capricious

Vision and Ethics Principles of Risk Assessment Risk Assessment - examples Weaknesses of Risk Assessment Beyond Risk Assessment to



“Children can develop and mature in an

environment that allows them to reach and maintain their full

potential.”

Vision for Child Health


“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


Socially responsible white guys?


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)


David Michaels

“Doubt is their product – How Industry’s Assault on Science Threatens Your Health”

2008 - Oxford

Tobacco, Chromium 6, second hand smoke ….


"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


“An ethic, ecologically, is a limitation on freedom of action in the struggle for

existence”Aldo Leopold

Limits on Freedom


“The Commons”

The Tragedy of the CommonsBy Garrett Hardin, Science, 1968


Technical Solutions

“It is our considered professional judgment that

this dilemma has no technical solution.”

The Tragedy of the CommonsBy Garrett Hardin, Science, 1968


Problems – Solutions?

Lead and kids Fetal alcohol syndrome Nuclear disarmament Bioterrorism Ocean Fisheries Persistent chemicals The Commons


"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


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


“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


• 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


Key Words of Toxicology

Hazard X Exposure = Risk

Individual Susceptibility

Dose / Response


Developed in 1960-1970s Concern over increased cancer ratesExpanded to non-cancer effects

Modern Risk Assessment


"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


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


Steps in Risk Assessment

Hazard IdentificationExposure AssessmentDose-Response AssessmentRisk Characterization


What Hazard?

ObviousDeath, Cancer, Acid burn, Birth defect, asthma …..

SubtleDecreases in learning and memory (lead)

Loss of potential

Sensitivity of the individual (child)


Hazard Identification

Review human and animal data to determine if a chemical or agent has biological effects.


Toxicity Endpoints

Carcinogenicity Mutations Altered immune function Teratogenicity Altered reproductive function Neuro-behavioral toxicity Organ-specific effects Ecological effects (wildlife,

environmental persistence)


Exposure Assessment

Route of exposure (skin, oral, inhalation)

Amount of exposure (dose)Duration of exposureTo whom (animals, humans,

environment) Children, other sensitive individuals


• Home environment• Workplace (occupational)• School• Food• Consumer products• Global and local environment

Exposure Issues


Dose-Response Assessment

How much exposure to a chemical or agent will cause what effect?

Dose – Response


Some Jargon

LOAEL – Lowest Observed Adverse Effect Level (mg/kg)

NOAEL – No Observed Adverse Effect Level (mg/kg)

RfD – Reference Dose (mg/kg-day)


Greater Dose – Greater Response

Dose

Res

po

nse

Threshold (NOAEL)

ED50

LOAEL


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


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


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


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)


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)


Mercury & Toxicology


The Mercury Cycle


Atmospheric Hg


• 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


Decrease in Brain Size Cell loss Disorganization of cells Cell migration failures Behavioral effects –

learning and memory

Effects On The Brain


Fetal Effects of MeHg


MONKEY - 25 µg/kg - LOAELRAT - 10 µg/kg - LOAELRAT - 50 µg/kg - replicated

Animal - Risk Assessment


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)


• 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.


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

GreekDioscerides - 2nd BC


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


Recycling Lead


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??


Community / Social Issues

Exposure Issues

Hazard / Toxicity


An approach to evaluating the scientific, safety, community, ethical, and social issues related to a compound or procedure.


Community / Social Issues G = Goal

N = Need

F = Future Generations

D = Democratic, community based process

A = Alternatives




Initial Parameter Score Comment

Community / Social Issues

Evaluate effects on the community and related social issues.

G G=Goal 1-31-a lot, 2-some, 3-little. Does this move forward the goal of human and environmental health?

N N=Need 1-31-a lot, 2-some, 3-little or not sure. Ask the question: Is it necessary? Do we really need this?

FF=Future Generations 1-3

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 process 1-3

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.

A A=Alternatives 1-3

1-alternatives were carefully considered, 2-some consideration, 3-no consideration. Where alternatives considered?

Total 5-155-good, supportive of health and community15-poor, not supportive of health or community


Exposure Issues E = Exposure

M = Multiple exposures

Ch = Children exposed

CP = Consumer products

O = Occupational exposure

F = Food exposure




Exposure Issues Evaluate potential exposure issues.

E E=Exposure 0-30-none, 1-little, 2-some, 3-high. Do we have control over the exposure?

MM=Multiple exposures 0-3

0-none, 1-little, 2-some, 3-high. Is there exposure to other chemicals with similar hazard?

ChCh=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.

CPCP=Consumer products 0-3

0-not in consumer products, 1-little, 2-some, 3- a lot or do not know. Is this compound in consumer products?

OO=Occupational exposure 0-3

0-no occupational exposure, 1-little, 2-some, 3- a lot or do not know. Is there occupational exposure?

FF=Food exposure 0-3

0-not in food supply, 1-little, 2-some, 3- a lot or do not know. Is the compound present in the food supply.

Total 0-200-no exposure, no problems20-significant exposure, serious concern


Hazard / Toxicity H = Hazard

IS = Individual Sensitivity

EC = Ecological hazard

UC = Uncertainty

V = Volume

P = Persistent




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)

ISIS=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.

ECEC=Ecological hazard 1-3

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 1-31-little persistence 2-some, 3-a lot of persistence or do not know. Is the compound presistent in the environment?

BB=Bioaccumulate 1-3

1-little 2-some, 3-a lot. Does it bioaccumulative in humans or animals or move up the food chain?

UCUC=Uncertainty 1-3 1-little 2-some, 3-a lot. How certain is the information?

Total 7-307-low hazard30-significant hazards or unknowns, serious concern


Community / Social Issues - 12/15

Exposure Issues – 16/20

Hazard / Toxicity – 27/30


Lead


• 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


“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


• 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


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


“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


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


Asthma & DiabetesSurvey Measures of Percent Ever Having Had Asthma and Diabetes Diagnoses, Seattle, 1994-

2002

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

1994 1995 1996 1997 1998 1999 2000 2001 2002

wei

gh

ted

per

cen

t o

f su

rvey

res

po

nd

ents

Data Source: Behavioral Risk Factor Surveillance System, Washington State Department of Health and Centers for Disease ControlPrepared by: Public Health- Seattle & King County, EPE, 5/04

asthma

diabetes (excluding during pregnancy)


Overweight & ObeseSurvey Measures of Percent Overweight and Obese, Seattle, 1994-2002

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

1994 1995 1996 1997 1998 1999 2000 2001 2002

year

wei

gh

ted

per

cen

t o

f su

rvey

res

po

nd

ents

overweight

obese

Data Source: Behavioral Risk Factor Surveillance System, Washington State Department of Health and Centers for Disease ControlPrepared by: Public Health- Seattle & King County, EPE, 5/04


The Precautionary Principle is part of the evolution in our

thinking and decision making toward ensuring human and

environmental health.

Conclusion


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)


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 Beyond Risk Assessment to Prec – 09/19/07Adapted 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


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


The Potential of Children


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


Risk Assessment

Documents

Precautionary Assessment