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Mey Akashah "Risk Assessment," Harvard


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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

Published in: Health & Medicine, Technology
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Mey Akashah "Risk Assessment," Harvard

  1. 1. Risk Assessment andImproved 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. 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. 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. 4. Risk Assessment: Components • Hazard Identification • Exposure Assessment • Dose-Response Assessment • Risk Characterization
  6. 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. 7. Hazard Identification: The ProcessGather information on: – Toxicity – Concentration – Potential routes of exposure – Receptor organs and tissues – Biochemical responses/Biotransformation
  8. 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. 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
  11. 11. Exposure AssessmentEvaluates how much hazard peoplecome into contact with, howoften, and for how long a period
  12. 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. 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. 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. 15. Exposure Assessment Toxicology
  16. 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 persons 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 doseNote: In many, many cases, you need to do a combinationof these!
  17. 17. Indirect: Ambient Measurement
  18. 18. Direct: Personal Measurement
  19. 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. 20. Axioms of Toxicology 1. People differ 2. Dose matters 3. Things change
  22. 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. 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. 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. 25. Potency and Dose-Response
  26. 26. Potency and Dose-ResponseNegative Biological Response TIME? Dose/Exposure (environmental toxin)
  27. 27. Axioms of Toxicology 1. People differ 2. Dose matters 3. Things change
  28. 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. 29. Dose-Responseand Regulatory Measurements
  30. 30. Dose-Response and RegulationNoncarcinogens: 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. 31. Cancer V. Non-CancerDose-Response Curves
  32. 32. Risk Assessment forCarcinogenic Effects
  33. 33. Cancer Risk (CR)• Cancer slope factor (CSF)• CR = intake estimate* X CSF* *mg/kg/day
  34. 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. 35. Risk Assessment forNon-carcinogenic Effects
  36. 36. NOAEL/LOAEL
  37. 37. NOAEL: no observed adverse effects levelLOAEL: lowest observed adverse effects level
  38. 38. LOAEL: lowest observed adverse effects level
  39. 39. NOAEL: no observed adverse effects level ? ? ?
  40. 40. THRESHOLD: level at which biological responses begin (may not be observable)NOAEL: no observed adverse effects levelLOAEL: lowest observed adverse effects level ? ?
  41. 41. Reference Dose = /UF (s) UFA UFH
  43. 43. 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.
  44. 44. hazard identification exposure assessmentdose-response assessment risk management and communication risk characterization risk assessment
  45. 45. 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
  46. 46. Examples of RiskCharacterization
  47. 47. 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‖
  48. 48. Examples of RiskCharacterization
  49. 49. 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)
  50. 50. 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!!!
  51. 51. 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)
  52. 52. 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.
  53. 53. Fish Consumption and Mercury Hg exposure in pregnant women may increase the risk of subtle neurotoxic effects in the fetus
  54. 54. Effect of Small Shifts in Population Mean Intelligence Quotient (IQ)
  55. 55. 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
  56. 56. 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
  57. 57. Classic Risk Assessment and Environmental Change
  58. 58. Classic Risk Assessment and Environmental Change Is the classic four-step risk assessment framework sufficient to examineenvironmental change, particularly climate change?
  59. 59. Example: Climate ChangeThree 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
  60. 60. ―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
  61. 61. An Applicable Maxim―All models are wrong, but some models are useful‖