Mey Akashah, "Risk Assessment and Improved Decision-Making," Harvard School of Public Health, Harvard Medical School, and Harvard Extension School, April 5 2012. Course: Human Health and Global Environmental Change

1. Risk Assessment and
Improved Decision-Making
Dr. Mey Akashah
Instructor, Harvard School of Public Health
Human Health and Global Environmental Change
April 5, 2012
Harvard School of Public Health (EH 278)
Harvard Medical School (HO703.0)
Harvard Extension School (ENVR E-165)

2. Regulations Based on Risk
Assessments
• Water discharge limits (EPA)
• Air emissions (EPA)
• Cleanup limits (EPA)
• Fish advisories or bans (EPA, DI)
• Product recalls
– Food/drugs/medical devices (FDA)
– Consumer products (CPSC)
• Workplace standards (OHSA)

3. Risk Assessment: A definition
―The characterization of the
potential adverse health
effects of human exposures
to environmental hazards.‖
―The Red Book‖
National Research Council. Risk Assessment in
the Federal Government: Managing the
Process, 1983

4. Risk Assessment: Components
• Hazard Identification
• Exposure Assessment
• Dose-Response Assessment
• Risk Characterization

5. HAZARD IDENTIFICATION

6. What is a hazard?
An agent capable of causing an adverse effect
• Combustible • Chemical
• Explosive • Non-ionizing radiation
• Toxic • Ionizing radiation
• Corrosive • Physical
• Biological • Noise
• Mechanical • Psychosocial

7. Hazard Identification:
The Process
Gather information on:
– Toxicity
– Concentration
– Potential routes of exposure
– Receptor organs and tissues
– Biochemical responses/Biotransformation

8. Hazard Identification:
The Data
• Historical information
• Chemical & related structures
• In vitro data
• In vivo data
– Animal studies
– Human studies
• Clinical trails (drugs)
• Occupational exposure
• Epidemiology
– Post-marketing surveillance

9. Hazard Identification
• Is the substance dangerous?
• What adverse effects are associated with the
toxicant? (e.g., neurological, immunological)
• Must evaluate quality of studies
– Choice of control groups, number of animals
– Severity of effect described
– Relevance of toxic mechanisms in animals to those
in humans
• Result: a scientific determination that a toxicant
can, at some exposure concentration, cause a
particular adverse health effect in humans

10. EXPOSURE ASSESSMENT

11. Exposure Assessment
Evaluates how much hazard people
come into contact with, how
often, and for how long a period

12. Concentration, Exposure,
& Dose
• Concentration:
– How much of a substance is present in
the medium
• Exposure:
– What we actually come into contact with
• Dose:
– The amount of the substance that enters
the body’s ―envelope‖

13. Exposure Versus Dose
Dose
• ―All things are poison and not
without poison; only the dose
makes a thing not a poison‖
OR
• ―The dose makes the poison‖
— Paracelsus
(1493-1541)

14. What do we mean by dose in
RAs?
• ―…the amount of a substance
administered at one time…‖
• Sometimes referred to as the
concentration of a substance in the
body ~ ―per mL blood‖ or ―amount per
kg body weight‖
• In environmental health, we often look
to ―cumulative exposure‖ as an
estimate of dose

15. Exposure Assessment Toxicology

16. Quantifying Exposures
• Indirect
– Involves collecting information about where, when, and
how people spend their time, and about the concentrations
of a contaminant in surrounding media.
– Ex. Ambient concentration
• Direct
– Assesses a person's exposure, using monitors attached to
the individual, or through the sampling of biological media
such as blood or urine.
– Ex. Direct personal exposure measurements (PEMs)
– Ex. Biological monitoring to capture dose
Note: In many, many cases, you need to do a combination
of these!

17. Indirect: Ambient Measurement

18. Direct: Personal Measurement

19. Imperfect…
• Exposureby an individual. provide a representation of the dose
received
assessments can
• However, whilean agent, many factors will determine the
concentration of
an individual may be exposed to a certain
biologically effective concentration for organs, tissues, and cells
• Individual and environmental factors effect dose!

20. Axioms of Toxicology
1. People differ
2. Dose matters
3. Things change

21. DOSE-RESPONSE
ASSESSMENT

22. Dose
• ―All things are poison and not
without poison; only the dose
makes a thing not a poison‖
OR
• ―The dose makes the poison‖
— Paracelsus
(1493-1541)

23. Individual Dose-Response Function
(Dose-Effect)
Example - Aspirin in humans
Severity
death
hemorrhage
encephalophathy
acidosis
hyperventilation
nausea
0 100 200 300 400 500 600
therapeutic
Dose (mg/kg)
Harvard Center for Risk Analysis

24. Dose-Response Assessment
• Involves quantitative characterization
of chemical potency
• Must understand importance of:
– intensity of exposure
– concentration over time
– whether a chemical has a threshold
– shape of the dose response curve
– metabolism at different doses
– persistence over time
– Similarities/differences in behavior of
chemical in humans and animals

25. Potency and Dose-Response

26. Potency and Dose-Response
Negative Biological Response
TIME?
Dose/Exposure (environmental toxin)

27. Axioms of Toxicology
1. People differ
2. Dose matters
3. Things change

28. Acute V. Chronic Toxicity
• Acute toxicity
– Describes the adverse effects of a substance that
can result exposures in a short space of time
(days to weeks)
– Animal Testing – single, high dose
• Chronic Toxicity
– Describes the adverse health effects from
repeated exposures, often at lower levels, to a
substance over a longer time period (months or
years)
– Animal Testing – multiple, low doses

29. Dose-Response
and Regulatory Measurements

30. Dose-Response and Regulation
Noncarcinogens: Threshold
Exposure level that is likely to
be without an appreciable risk of
deleterious effects during a lifetime
Carcinogens: Nonthreshold
There is no exposure level that
does not pose a finite probability of
generating a carcinogenic response,
i.e., there is a risk associated with
any exposure level

31. Cancer V. Non-Cancer
Dose-Response Curves

32. Risk Assessment for
Carcinogenic Effects

33. Cancer Risk (CR)
• Cancer slope factor (CSF)
• CR = intake estimate* X CSF*
*mg/kg/day

34. Cancer Potency Estimates (CPE)
• Estimated upper bound on lifetime cancer
risk associated with the lifetime daily dose
of a chemical
• CPE developed by different regulatory
agencies for the same chemical can vary
substantially
– Level of risk sufficient to trigger
regulatory can vary considerably among
agencies and within an agency

35. Risk Assessment for
Non-carcinogenic Effects

36. NOAEL/LOAEL

37. NOAEL: no observed adverse effects level
LOAEL: lowest observed adverse effects level

38. LOAEL: lowest observed adverse effects level

39. NOAEL: no observed adverse effects level
? ? ?

40. THRESHOLD: level at which biological responses begin
(may not be observable)
NOAEL: no observed adverse effects level
LOAEL: lowest observed adverse effects level
? ?

42. Reference Dose = /UF (s)
UFA UFH

44. RISK CHARACTERIZATION

45. Risk Characterization
• A synthesis and summary of information
about a hazard that addresses the needs and
interests of decision makers and of interested
and affected parties.
• Risk characterization is a prelude to decision
making and depends on an iterative, analytic-
deliberative process.
Report by the National Academy of Sciences' National Research
Council, 1996.

46. hazard
identification
exposure
assessment
dose-response
assessment
risk
management
and
communication
risk
characterization
risk assessment

47. Goal is rarely ―no risk‖
• Environmental risk assessments deal with
the incremental probability of some harm
occurring.
• For example, EPA attempts to control
exposure to toxicants to levels that will
pose incremental lifetime cancer risk
among the most exposed to roughly 1 to
100 additional cancers per 1 million
people

48. Examples of Risk
Characterization

49. Cost-Benefit Analysis
• Systematic process for calculating and
comparing benefits and costs of an
intervention, project, change in policy
• Benefits and costs expressed in terms of
monetary equivalents
– These are adjusted for the ―time value of
money‖

50. Examples of Risk
Characterization

51. Public Perceptions about Risk
• Preceding tables often used to put risk into
perspective for public
• Often, these numbers seem reasonable to those
familiar with the RA process, but confusing and
sometimes frightening for the public
• Factors affecting fear around risks:
– Lack of control over risk
– Lack of familiarity with risk (unknown risks scarier
than known risks
– Natural risks more acceptable (earthquakes Vs. plant
explosions, cars Vs. sharks)

52. Risk Characterization
• Where all the information comes together!
• Integrates hazard identification, dose-response
assessment, & exposure assessment
• Requires making scientific judgments:
– What do exposure data mean?
– Is dosage information available?
– How do exposures compare with doses used in
animal studies? Human data?
– Are doses higher than allowed?
– Should report all uncertainties & assumptions!!!

53. Important Types of Uncertainty
• Parameter uncertainty
– we know that we don’t know it.
• Measurement errors
• Sampling errors
• Use of ―generic‖ data when actual data exists
• Scenario uncertainty
– Uncertainty regarding missing or incomplete information
needed to fully define the exposure or dose (i.e., errors in
information)
• Model uncertainty
– we may not know that we don’t know it (i.e., we chose the
incorrect model)
• Uncertainty regarding gaps in scientific theory required to make
predictions on the basis of causal inferences (model structure –
linear vs. nonlinear)

54. Why is it important to characterize
uncertainty and variability?
• We are not concerned about uncertainty for
its own sake, but rather how it influences
our decisions.
• We need to characterize uncertainty for risk
management decisions.
• It is generally not received well by the
public but it needs to be done.

56. Fish Consumption and Mercury
Hg exposure in pregnant women may
increase the risk of subtle
neurotoxic effects in the fetus

57. Effect of Small Shifts in Population
Mean Intelligence Quotient (IQ)

58. Fish Advisories:
The Good and the Bad
• Good: Polyunsaturated fatty acids
• Bad: Hg (among other things)
• Science  Policy  Interpretation
– Science: complex
– Policy simplified for general consumption
• Interpretation of Public: Avoid fish
altogether

59. Risk Assessment Vs.
Risk Management
• Risk Assessment
– The characterization of the potential adverse health effects of human
exposures to environmental hazards
• Risk Management
– Agency-based decision-making process
– Uses the knowledge gained from risk assessment to evaluate
alternative regulatory actions and select among them
– Entails consideration of political, social, economic, and engineering
information with risk assessment information to develop, analyze, and
select regulatory guidelines
– Requires the use of value judgments on acceptability of risk and the
reasonableness of the costs of control

60. Classic Risk Assessment and
Environmental Change

61. Classic Risk Assessment and
Environmental Change
Is the classic four-step risk assessment
framework sufficient to examine
environmental change, particularly climate
change?

62. Example: Climate Change
Three key considerations:
• System complexity
– Including cyclical risks
• Multiplicative uncertainty
– Each uncertain variable propagates uncertainty
• Sample size
– Limited data on climactic response to current
levels of atmospheric particulates

63. ―Non-Classic‖ approaches to
climate change using RA
• IFRC Vulnerability and Capacity Assessment tool
• UNDP Global Risk Assessment Programme
• UK Climate Change Risk Assessment methodology
• Australia-New Zealand Standard (assessments of
climate change risks)
• …
• Most include both risk assessment and risk
management in one framework

64. An Applicable Maxim
―All models are wrong, but some models are
useful‖