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 Use of chemical-specific data in lieu of defaults  Proposed Methods  Evaluate approach in Silver Book/EPA’s draft guidance with boron as an example  Suggestions for Improvement  Review guidance from other sources (e.g., IPCS)  Evaluate the uncertainty associated with defaults 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)