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 Assessment

1. 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

LOAEL

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 exposure

What 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

Factor

Animal to Human (H) 10

Average to Sensitive Human (S) 10

LOAEL to NOAEL (L) 10

Less than Chronic to Chronic (C) 10

Data Quality (MF) 1-10

Ex. Drinking water contaminants

Suppose 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?

Got Mercury ?

http://gotmercury.org/article.php?id=1034

Perception of Risk

Attributes that elevate perception of risk Attributes that lower perception of risk

Involuntary 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