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Beyond Science and Decisions

Beyond Science and Decisions. TCEQ Workshop I Austin, Texas March 16-18, 2010 Bob Benson EPA Region 8 March 17, 2010. Bob Benson’s House. Science and Decisions: Advancing Risk Assessment Chapter 5 Toward a Unified Approach to Dose-Response Assessment.

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Beyond Science and Decisions

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  1. Beyond Science and Decisions TCEQ Workshop I Austin, Texas March 16-18, 2010 Bob Benson EPA Region 8 March 17, 2010

  2. Bob Benson’s House

  3. Science and Decisions:Advancing Risk AssessmentChapter 5Toward a Unified Approach to Dose-Response Assessment

  4. A Perspective from an EPA Regional ScientistDisclaimer: The views in this presentation do not reflect the views and policies of the US EPA

  5. Problems Identified by NAS PanelCancer Assessments: • Inter-human variability in risk either not addressed (animal studies) or incompletely addressed (epidemiological studies) • Uncertainty in risk not characterized • Low dose, non-linear assessments (RfD approach) do not present a risk measure (risk below RfD = 0)

  6. Problems Identified by NAS PanelNon-Cancer Assessments: • Possibility for low dose linearity not addressed • No risk measure presented. Risk below RfD = 0. HI, RfD, MOE of limited utility for risk-benefit analyses. • Uncertainty not distinguished from variability

  7. Characteristics of the NAS Recommended Dose-Response Framework • Use spectrum of evidence from human, animal, mechanistic, and other relevant studies (in absence of chemical specific information use defaults based on evidence from other chemicals) • Adopt risk-specific Reference Dose • Use distributions rather than point values for uncertainty factors

  8. Risk Specific Reference Dose • Dose that corresponds to a particular risk specified to be de minimus (for example, 1 in 100,000) at a defined confidence level (for example, 95%) for the endpoint of concern. It can be derived by applying human variability and other adjustment factors (for example, for interspecies differences) represented by distributions rather than default uncertainty factors.

  9. Using a risk standard of 1 in 100,00 is too low to be practical for hazardous waste sites in EPA Regions

  10. What does a 1 in 100,000 probability of a 10% increase in liver weight mean? What is the cost (willingness to pay) to correct the condition?

  11. Characteristics of the NAS Recommended Dose-Response Framework • Quantitative consideration of human variability • Quantitative consideration of uncertainty • Evaluate background exposure and background disease process to select modeling approach (linear or non-linear)

  12. Consideration of Background Exposure

  13. Summary of Cancer Risk from Arsenic to an Adult Fisherman Compared to Risk to a Resident -- = incomplete pathway *Risks from exposure to sediment have been summarized in the "soil" category for the fisherman. **Risks from exposure to diet have been summarized for fish tissue for the fisherman.

  14. Characteristics of the NAS Recommended Dose-Response Framework • Extrapolate from human POD to low dose where response = 1 in 100,000 • Default extrapolation using linear model in most cases (slope = 1)

  15. Current Uncertainty Factors used to derive a RfD • Subchronic to chronic • Data base deficiency • Animal to human extrapolation • Inter-human variability

  16. Source of distributions to replace uncertainty factors • Distributions from an analysis of uncertainty factors from a random sampling of IRIS files • Distributions from an analysis of data from pharmaceuticals

  17. Is it an advance to replace point values for uncertainty factors with a distribution that is not derived from the chemical of concern?

  18. Alternative Source of distributions to replace uncertainty factors • Distributions in internal dose (PK) in lab animals and humans with the chemical of interest • Distributions in PD in lab animal and humans (Tox Testing in 21st Century)

  19. A Proposal for Cost-Benefit Analyses Many EPA statutes require cost-benefit analyzes in the rule making.

  20. BMD10 = 3.62BMDL10 = 2.78RfD = BMDL10/10x10 = 0.03Response at RfD = 0 to 1 in 1,000 (95% UCL)

  21. BMD10 = 80.3BMDL10 = 65.8RfD = BMDL10/10x10 = 0.7Response at RfD = 0 to 1 in 1,000 (95% UCL)

  22. Thank You!

  23. What about thresholds?

  24. Toxicologists: A threshold exists! There must be an exposure below which no biologically significant response occurs

  25. Statisticians: A threshold can’t be verified! A response follows a linear relationship. Any exposure greater than 0 will cause some response. The slope isn’t always equal to 1.

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