1. Introduction to Risk Assessment
EH202
April 26, 2009

2. 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

3. Cayuga River Fire,
New York (1965)

4. Love Canal, New York
1942
Love Canal, New York
1978

5. Valley of the Drums
Louisville, Kentucky (1979)

6. Superfund Site
Nassau County, New York

7. Location of National Priority List (NPL) Hazardous Waste Sites

8. 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?

9. 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

10. “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.

11. 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)

12. Four Steps of Risk Assessment
Hazard Identification – the process of determining a particular chemical is causally linked to particular health effects
Dose-Response Assessment – process of characterizing the relationship between the dose of an agent and the incidence of an adverse health effect
Exposure Assessment – involves determining the size and nature of the population that has been exposed to the toxicant under consideration
Risk Characterization – integration of the above three steps which produces an estimate of the magnitude of the public-health problem

13. 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

14. Philippe Grandjean

15. The Dose-Response Obtain a mathematical relationship between the amount of a toxin an individual is exposed to and an adverse health response Frequently only have animal test data
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0.9 1
LOAEL
Proportion Responding
NOAEL 2 4 6 8 10
Dose (mg/kg/day)
Harvard Center for Risk Analysis

16. 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
Response
Experimental Region
Dose
Human Exposure Region

17. 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:
Direct personal exposure measurements
Build exposure model using concentration measurements
Fate and transport model to estimate/simulate exposures
Biomonitoring to capture dose measures

18. 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?

19. Risk Characterization Cancer 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 factor
Where,
CDI = Average daily dose (mg/day)
Body weight (kg)

20. Example: Benzene emissions
Suppose 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?

22. 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?

23. 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

25. Ex. Drinking water contaminants
Suppose drinking water contains 1.0 mg/L of toluene and has a RfD of 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?

26. Ex. Tuna How could you estimate exposure? How could you estimate dose?
Measure the environment—the amt of mercury in the tuna. Do biological monitoring---blood or urine.

27. Back to tuna … What is the exposure? What is the dose?
Methylmercury
Range
Mercury
TUNA, fresh
0.22
0-0.9
0.69
TUNA, canned
0.17
0-0.75
0.2
TUNA, white albacore canned
0.24
0-0.49
0.36
TUNA, albacore canned --
0.35
TUNA, chunk light tongol
0.08
TUNA, canned chunk light
0.19
0-0.18
0.12
0-0.72
FDA maximum permissible level of 1 ppm in seafood
acceptable daily intake (ADI) for methylmercury (as mercury) of 30 µg and assumes a maximum fish ingestion rate of 30 g/day--the equivalent of one 7-8 oz serving per week--by a 70-kg adult. Higher ingestion rates, lower body weights, higher mercury levels in the fish, or a combination of these factors would result
.17 ug/gram *3.491 gram/day = 0.6 ug/day … need to divide by BW (0.009 ug/kg)
Provisional tolerable weekly intake (PTWI) of 1.6 µg/kg bw – WHO (0.22 ug/kg bw)
FDA maximum permissible level of 1 ppm
Data from FDA

28. NEJM 2002; 347:1735

29. US EPA
Exposure Factors Handbook

30. What is average mercury dose?

31. Got Mercury ?

32. 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)

33. 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
Flying 6000 miles by jet
Cancer by cosmic radiation
Traveling 10 miles by bicycle
Living 2 months with a cigarette smoker
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