Introduction to Risk Assessment
EH202April 26, 2009
Origin of risk assessment
• Early days of EPA (1970s)– Visible and demonstrable environmental hazards
– Federal standards and enforcement provisions seen as solution
– Little focus on impact of pollution on environment and public health and intrinsic assumption that pollutants have thresholds
Cayuga River Fire,New York (1965)
Love Canal, New York1942
Love Canal, New York1978
Valley of the Drums Louisville, Kentucky (1979)
Superfund SiteNassau County, New York
Location of National Priority List (NPL) Hazardous Waste Sites
• In ‘70s and ‘80s growing interest in toxic chemicals and their effect on cancer
• Cancer rates associated with toxic exposures are unobservable in most circumstances
• Acceptable level of risk generally 1-in-a-million
• If any exposure to a substance causes some risk, how can standards be set?
• When cleaning up a hazardous waste site, at what point is the project completed?
What is risk assessment?
• The process of identifying and evaluating adverse events that could occur in defined scenarios
• A quantitative framework for evaluating and combining evidence from toxicology, epidemiology, and disciplines, with a goal of providing a basis for decision making
• “Risk assessment ... is a way of examining risks so that they may be better avoided, reduced, or otherwise managed ...”
• “Risk assessments, except in the simplest of circumstances, are not designed for making judgments, but to illuminate them ...”
Source: Wilson and Crouch, Science, 1987.
Evaluate the risk, Then decide what to do…
Risk assessment is the use of the factual base to define the health effects of exposure of individuals or populations to hazardous materials and situations
Risk management is the process of weighing policy alternatives and selecting the most appropriate regulatory action ... integrating the results of risk assessment with social, economic, and political concerns to reach a decision
National Research Council (1983)
Four Steps of Risk Assessment1. Hazard Identification – the process of determining a particular
chemical is causally linked to particular health effects
2. Dose-Response Assessment – process of characterizing the relationship between the dose of an agent and the incidence of an adverse health effect
3. Exposure Assessment – involves determining the size and nature of the population that has been exposed to the toxicant under consideration
4. Risk Characterization – integration of the above three steps which produces an estimate of the magnitude of the public-health problem
Hazard Identification• Examines the evidence that associates exposure to an agent with its
toxicity or potential to cause harm
• Collection of data– Various sources– Toxicological and epidemiological studies
• Information should answer these questions– Does exposure to the substance produce any adverse effects?– If yes, what are the circumstances associated with the exposure?
• Produces a qualitative judgment about the strength of that evidence
Philippe Grandjean
Harvard Center for Risk Analysis
The Dose-Response Obtain a mathematical relationship between the amount of a toxin
an individual is exposed to and an adverse health responseFrequently only have animal test data
Dose (mg/kg/day)
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NOAEL
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Applying toxicology• The dose is an exposure averaged over a specific length of time
– Usually assume a lifetime of exposure (70 yrs)• The response (risk) has no units
– It is a probability of an adverse effect• Extrapolate from high to low dose• Assumes response in animals is comparable to humans
Dose
Experimental Region
Human Exposure Region
Response
Exposure Assessment• Process of measuring or estimating the intensity,
frequency, and duration of human exposure to an agent present in the environment, or estimating the exposures that might occur from the release of new chemicals
Quantifying Exposures:1. Direct personal exposure measurements2. Build exposure model using concentration
measurements3. Fate and transport model to estimate/simulate exposures4. Biomonitoring to capture dose measures
Exposure Assessment – a few issues to consider
• Exposure to whom?– Sensitive subpopulations
• Exposure over what time period?– Lifetime exposure, peak exposure, etc.
• Exposure through which pathway?– Inhalation, food consumption, drinking water, dermal
exposure
• Do important factors modify the concentration-exposure relationship?
• What about the exposure-dose relationship?
Risk CharacterizationCancer vs Non-Cancer
• Cancer is treated as a stochastic response– Any dose carries a risk– Increasing dose of chemical doesn't increase the severity of the
response, only the likelihood that it will occur
• Potency – slope of the dose response curve
Incremental lifetime cancer risk = CDI * potency factorWhere,
CDI = Average daily dose (mg/day)Body weight (kg)
Example: Benzene emissionsSuppose an industrial facility that emits benzene is being proposed for a site near a residential neighborhood. Air quality models predict that 6-% of the time, prevailing winds will blow benzene away from the neighborhood but 40% of the time, the benzene concentrations will be 0.01 mg/m3. Should this plant be allowed to be built?
What information do you need to calculate the chronic daily intake?
Ex. An occupational exposureWhat is the incremental cancer risk for a 60- kilogram worker exposed to a carcinogen that has a potency factor of 0.02 mg/kg/day 5 days per week, 50 weeks per year, over 25 year period?
Non-Cancer Risk Assessment• Non-cancer responses are considered deterministic
– Thresholds exist– Exposure below the threshold poses no risk
• Reference Dose– obtained by dividing the NOEL by uncertainty factors and is expressed in mg/kg/day
Hazard Quotient = Average daily dose during exposure period (mg/kg/day)RfD
U.S. EPA Guidelines for Development of RfD*Extrapolation Uncertainty
FactorAnimal to Human (H) 10Average to Sensitive Human (S) 10LOAEL to NOAEL (L) 10Less than Chronic to Chronic (C) 10Data Quality (MF) 1-10
Ex. Drinking water contaminantsSuppose drinking water contains 1.0 mg/L of toluene and has a RfD of 0.200 mg/kg-day based on changes to the liver and kidneys. A 70 kg adult drinks 2-L per day of this water for 10 years. Is this a safe exposure?
Ex. Tuna
• How could you estimate exposure?
• How could you estimate dose?
Back to tuna …What is the exposure? What is the dose?
Methylmercury Range Mercury Range
TUNA, fresh 0.22 0-0.9 0.69 0.38-1.14
TUNA, canned 0.17 0-0.75 0.2 0.06-0.35
TUNA, white albacore canned 0.24 0-0.49 0.36 0.03-0.86
TUNA, albacore canned -- -- 0.35 0.29-0.85
TUNA, chunk light tongol -- -- 0.08 0.05-0.18
TUNA, canned chunk light 0.19 0-0.18 0.12 0-0.72
Data from FDAFDA maximum permissible level of 1 ppm
NEJM 2002; 347:1735
US EPAExposure Factors Handbook
http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=12464
What is average mercury dose?
Perception of Risk
Attributes that elevate perception of risk Attributes that lower perception of riskInvoluntary Voluntary
Exotic Familiar
Uncontrollable Controllable
Controlled by others Controlled by self
Dread Accept
Catastrophic Chronic
Caused by humans Natural
Inequitable Equitable
Permanent effect Temporary effect
No apparent benefit Visible benefits
Unknown Known
Uncertainty Certainty
Source: Based on Slovic (1987) and Slovic et al (1980)
Activities that increase mortality risk by one in a million
Activity Types of risk
Smoking 1.4 cigarettes Cancer, heart disease
Drinking ½ liter of wine Cirrhosis of the liver
Spending 1 hour in a coal mine Black lung disease
Living 2 days in New York or Boston Air pollution
Travelling 300 miles by car Accident
Flying 1000 miles by jet Accident
Flying 6000 miles by jet Cancer by cosmic radiation
Traveling 10 miles by bicycle Accident
Living 2 months with a cigarette smoker Cancer, heart disease
Eating 40 tablespoons of peanut butter Liver cancer caused by aflatoxin
Living 50 years within 5 miles of nuclear reactor Accident releasing radiation
Source: Wilson 1979