Advancing Risk Assessment: Science and Decisions

1. Science and Decisions: How Can We Advance Risk Assessment?The Collaborative on Health and the Environment Tom Burke Professor and Associate Dean Johns Hopkins Bloomberg School of Public Health May 24, 2011

2. SCIENCE AND DECISIONS: ADVANCING RISK ASSESSMENT National Research Council Committee on Improving Risk Analysis Approaches Used by EPA Board on Environmental Studies and Toxicology

3. Risk Assessment Risk assessment is a process in which information is analyzed to determine if a hazard may cause harm. The goal is to provide the best possible characterization of risk based upon a rigorous evaluation of available information and knowledge.

4. Uses of Risk Assessment • Essential to public health decisions • Food safety • Emergency response • Drinking water, air, clean up standards • Virtually all regulatory and public health decisions use some form of risk assessment

5. Is risk assessment broke? • Credibility is being challenged by stakeholders • Easy target for raising doubts • Surrogate for conflicts over risk management costs • Disconnect between available data and needs of decision makers • Appropriate for new challenges, cumulative risk, energy, built environment, sustainability?

6. Quiz Political conflicts concerning the potential costs of risk management should influence which of the following? • The selection of epi or tox studies for the risk assessment • The shape of the dose-response curve • The RfD or cancer slope factor • The level of acceptable uncertainty • The choice of risk management options

7. REPORT CONCLUSIONS AND RECOMMENDATIONS Design of risk assessment Uncertainty and variability Selection and use of defaults Unified approach to dose-response assessment Cumulative risk assessment Improving the utility of risk assessment Stakeholder involvement Capacity-building

8. UNCERTAINTY The level of detail for characterizing uncertainty is appropriate only to the extent that it is needed to inform specific risk-management decisions appropriately. Inconsistency in the treatment of uncertainty among components of a risk assessment can make the communication of uncertainty difficult and sometimes misleading.

9. The Big Uncertainty: Low Doses Dose-Response Curve R e s p o n s e Observable Range Range of Inference 0 Dose 9

10. VARIABILITY Variability in human susceptibility has not received sufficient or consistent attention in EPA health risk assessments Committee encourages EPA to move toward the long-term goal of quantifying population variability more explicitly in exposure assessment and dose-response relationships.

11. Susceptible Subgroupsin the Population Source: Tarcher (adapted)

12. SELECTION AND USE OF DEFAULTS Established defaults need to be maintained for the steps in risk assessment that require inferences and that clear criteria should be available for judging whether, in specific cases, data are adequate for direct use or to support an inference in place of a default. EPA, for the most part, has not yet published clear, general guidance on what level of evidence is needed to justify use of agent-specific data and not resort to a default. There are also a number of defaults (missing or implicit defaults) that are engrained in EPA risk-assessment practice but are absent from its risk-assessment guidelines.

13. Default Examples • For carcinogens, there is a linear increase in risk as dose or exposure increases • We all drink 2 liter of water a day • We all weigh 70 kg • If we don’t have data the risk is zero

14. SELECTION AND USE OF DEFAULTS Evidentiary Standard for Replacing Default “The committee recommends that EPA adopt an alternative assumption in place of a default when it determines that the alternative is ‘clearly superior’, that its plausibility clearly exceeds the plausibility of the default.”

15. UNIFICATION APPROACH TO DOSE-RESPONSE ASSESSMENT Historically, dose-response assessments at EPA conducted differently for cancer and noncancer effects Methods have been criticized for not providing the most useful results. A consistent approach to risk assessment for cancer and noncancer effects is scientifically feasible and needs to be implemented.

16. Current Approach to Dose-Response Assessment

17. Unification • Does not mean that there are no thresholds or that every chemical behaves like a carcinogen. • It is about our way of characterizing risks.

18. CUMULATIVE RISK ASSESSMENT EPA is increasingly asked to address broad public-health and environmental-health issues that stakeholder groups often consider inadequately captured by current risk assessments multiple exposures complex mixtures vulnerability of exposed populations There is a need for cumulative risk assessments as defined by EPA that include combined risks posed by exposure to multiple agents or stressors aggregate exposure to a given agent or stressor all routes, pathways, and sources of exposure Chemical, biologic, radiologic, physical, and psychologic stressors are considered.

19. SINGLE POLLUTANT SINGLE MOA SINGLE PATHWAY SINGLE POPULATION SINGLE ROUTE TRADITIONAL RISK ASSESSMENT

20. MULTI-POLLUTANT COMMON/MULTIPLE MOA MULTI- PATHWAY MULTI-ROUTE MULTIPLE POPULATIONS MULTI-POLLUTANT CUMULATIVE RISK ASSESSMENT

22. Bottom Line on Silver Book • Informing the decisions – Problem formulation • Refining the methods • Consideration of population susceptibility and cumulative impacts • New framework • Ending the quagmire