Breakout Group C

Jennifer Seed (Chairwoman), Allison Jenkins (Rapporteur ),

Janet Kester, Daniele Staskal,

Gulan Sun, Valerie Meyers (phone),

Andy Maier (phone), Bob Budinsky (phone),

Ted Simon (phone)

Case Study Proposal #8

• Exploring three conceptual models for individual/population dose response using 2,3,7,8-trachlorodibenzodioxin (TCDD) as an example. TCDD is data-rich and would permit exploration of all three models.

• Ted Simon, Bob Budinsky, J. Craig Rowlands• Very well described, draft proposal completed• Existing publication (Simon 2009) and Simon et

al. (unpublished)

Case Study Proposal #20• #20 – Three nuclear receptors, AHR, CAR/PXR and

PPARα, will be used as examples for how their biology can be used to define mode of action and dose-response for liver tumors in rodents.

• Teams are in the process of developing case studies for September 2010 Nuclear Receptor Workshop

• Breakout Group C proposes to link case study proposals #20 (general) and #8 (specific example)

• #20 (or similar) will be prepared for September 2010 Nuclear Receptor Workshop.

Case Study Proposals #6, #25

• Screening proposals

• Easily Accomplished

• Recommend problem formulations are expanded in both case study proposals

Case Study Proposal #15

• Ongoing chromium MOA study to address data gaps in the knowledge of its mode of action.

• Data will not be completed by date of 2nd ARA Workshop

• Breakout Group C proposes to ‘table’ Proposal #15 for consideration at ARA Workshop 2

Idea for Case Study

• DNA damage by intracellularly generated formaldehyde has been proposed as a carcinogenic mode of action for several chemicals (e.g., methanol, MTBE).

• Data on formaldehyde-DNA adduct formation can be used to evaluate this hypothesis.

• Unknown if sufficient data exist.• Janet Kester is contact person.