Case Study # 2

1. Case Study # 2 • Problem Formulation • Inter-individual variability in cancer assessment (evaluate default from Silver Book) • Proposed Methods • Critical review of method outlined in Silver Book • Suggestions for Improvement • Refinement/expansion of methodology • Consider as case study? • Yes (with additional refinement)

2. Case Study # 7 • Problem Formulation • Preexisting disease and low dose linear non cancer response • Proposed Methods • Critical review of methodology provided in Silver Book • Suggestions for Improvement • Provide methodology for evaluating this question • Consider as case study? • No (not in its current form)

3. Case Study # 10 • Problem Formulation • Uncertainty in dose-response assessment • Proposed Methods • Using sensitivity analyses, compare the uncertainty associated with the BBDR model for formaldehyde with default methods • Suggestions for Improvement • Could be combined with PBPK model for formaldehyde • Consider as case study? • Yes

4. Case Study # 23 • Problem Formulation • Species differences in metabolism • Proposed Methods • Evaluate the differences in metabolism for 1,3-butadiene and the impact on disease outcomes • Suggestions for Improvement • Consider as case study? • Yes

5. Case Study # 23.2 • Problem Formulation • Using human data in cancer risk assessment • Proposed Methods • Epidemiological investigations of 1,3-butadiene and leukemia • Suggestions for Improvement • Use MOA to interpret the epidemiology data • Consider as case study? • Yes

6. Case Study # 25 • Problem Formulation • Developing acute air screening levels • Proposed Methods • TCEQ approaches for developing effects screening levels (pentene as an example) • Suggestions for Improvement • Consider as case study? • Yes

7. Case Study # 6 • Problem Formulation • Developing screening levels for chemicals with minimal data using structure or class information • Proposed Methods • Proposes using a range of tools including QSAR • Suggestions for Improvement • There may be other relevant tools to consider • Consider as case study? • Yes

8. Case Study # 1(b) • Problem Formulation • Use of chemical-specific data in lieu of defaults • Proposed Methods • Evaluate approach in Silver Book/EPA’s draft guidance with boron as an example • Suggestions for Improvement • Review guidance from other sources (e.g., IPCS) • Evaluate the uncertainty associated with defaults • Consider as case study? • No (not in its current form)