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Hypothesis-Based Weight of Evidence and its Role in Characterizing Uncertainty in Risk Assessment

Main Components of Uncertainty. Is each potential endpoint a human-relevant hazard?Choice of dataset to represent human risk D-R model fitUncertainty in response measureUncertainty in dose measureLow-dose extrapolation of high-dose effectsToxicologic equivalency of exposures across species. .

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Hypothesis-Based Weight of Evidence and its Role in Characterizing Uncertainty in Risk Assessment

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    1. “Hypothesis-Based Weight of Evidence and its Role in Characterizing Uncertainty in Risk Assessment"

    2. Main Components of Uncertainty Is each potential endpoint a human-relevant hazard? Choice of dataset to represent human risk D-R model fit Uncertainty in response measure Uncertainty in dose measure Low-dose extrapolation of high-dose effects Toxicologic equivalency of exposures across species

    3. FOR HUMAN RISK ESTIMATION:

    4. Where QRA Uncertainty Gets Stuck

    5. Weight-of-Evidence for Human Carcinogenicity (Hazard ID)

    6. Weight-of-Evidence for Human Carcinogenicity (Hazard ID)

    7. Weight-of-Evidence Factors

    8. Weight-of-Evidence for Human Carcinogenicity (Hazard ID)

    9. Carcinogen WoE & QRA -- Current

    11. “WEIGHT OF EVIDENCE”

    12. “WEIGHT OF EVIDENCE”

    13. Endpoint-by-Endpoint Evaluation of Data

    14. Endpoint-by-Endpoint Evaluation of Data

    15. Articulate an Hypothesis

    16. Articulate an Hypothesis

    17. Articulate an Hypothesis

    18. Evaluate How Compelling the Case is for the Proposed Basis of Human Risk in View of:

    19. Evaluate How Compelling the Case is for the Proposed Basis of Human Risk in View of:

    20. Hypotheses (and the Human Risk Projections They Entail) are Compelling to the Extent That:

    21. Endpoint-by-Endpoint Evaluation of Data

    22. Evaluating Hypotheses Against the Data

    23. Can (and should) also Evaluate Hypotheses About Lack of Human Carcinogenic Risk

    24. For Each Hypothesis…

    26. Does THIS ENDPOINT constitute a Human Hazard?

    27. OVERALL WoE is Secondary to the Set of Endpoint-Specific WoE

    28. Advantages of Hypothesis-Based WoE

    29. QRA

    30. QRA Uncertainty Characterization

    31. Advantages of Hypothesis-Based WoE Gives some measure of how compelling the evidence is for each endpoint Gives structure and substance to the overall WoE Gives context for model and dataset choices; ties QRA to WoE Not just one endpoint to represent all possible human risks Lays out reasoning; transparent

    32. Is This Just…

    33. Help from Epistemology in Gauging WoE and Evaluating Hypotheses Against Data

    34. Considerations in Evaluating a Theory

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