Dose-Response Approaches for Nuclear Receptor-Mediated Modes of Action
What: Dose-Response Approaches for Nuclear Receptor-Mediated Modes of Action Workshop
When: September 27-29, 2010
Where: NIEHS Facility, Research Triangle Park
Workshop begins: Monday, September 27 at 8 AM (Eastern)
Workshop ends: Wednesday, September 29 at 1 PM (Eastern)
In-person space is limited and almost filled. After registration is full, please register for the webcast only.
This workshop will explore the development of dose-response approaches to nuclear receptor-mediated liver cancer, including biologically-based dose-response (BBDR) models for key events leading to apical outcomes for tumor promoters. The presence of threshold effects for non-cancer and (in appropriate cases) cancer has been the dominant paradigm for the practice of risk assessment. The application of dose-response modeling approaches that include a threshold, however, has been recently questioned (White, et al., 2009; NAS, 2008). The growing body of molecular toxicology information is allowing us to explore the presence or absence of sub-threshold doses for a number of receptor-mediated modes of action. This workshop will explore the biology and dose-response implications of such information for a number of nuclear receptors for which computational systems biology will be applied along with conventional measures of toxicity and mode-of-action information. Click here for a brochure on the workshop.
Workshop Co-Chairs
Melvin Andersen, The Hamner Institutes for Health Sciences
Julian Preston, U.S. EPA
Steering Committee
Richard Becker, American Chemistry Council
Robert Budinsky, Dow Chemical Co.
Michael Cunningham, NIEHS
Vicki Dellarco, U.S. EPA
Michael Dourson, Toxicology Excellence for Risk Assessment
Cliff Elcombe, CXR Biosciences, University of Dundee Medical School
James Klaunig, Indiana University
Michael Honeycutt, Texas Commission on Environmental Quality
Sponsors
Alliance for Risk Assessment
American Chemistry Council’s Center for Advancing Risk Assessment Science and Policy
Chlorine Chemistry
CropLife America
CXR Biosciences
DuPont
The Hamner Institutes for Health
Indiana University, Dept. of Environmental Health
Society of Toxicology
Society for Risk Analysis
3M Company
Toxicology Excellence for Risk Assessment
U.S. EPA, National Health and Environmental Effects Research Laboratory
U.S. EPA, Office of Chemical Safety and Pollution Prevention
Workshop Objectives
1. Determine whether the biology of nuclear receptors necessitates a minimum threshold of ligand to be available for activation of a receptor in order to affect gene expression;
2. Determine whether a minimum threshold of receptor ligand is required for any induced effects and subsequent biological and toxicological responses;
3. Determine whether linear low-dose modeling of receptor ligands is appropriate, based on the underlying science of nuclear receptor signaling biology, and if not, provide insights into more appropriate low-dose modeling approaches;
4. Develop peer reviewed publications that will serve as a resource for regulators and scientists to refer to for guidance on selecting appropriate low-dose response modeling of nuclear receptor ligands.
Case Study Break-Out Sessions
Case studies will be addressed for three nuclear receptors of toxicologic importance: AHR, CAR/PXR, PPARα. Case studies include presentations and break-out sessions with panels of experts. The goal is to identify consensus and divergent opinions regarding dose-response implications of receptor biology with incorporation of mode of action data. An outcome will be identification of data gaps in the underlying MOA data and dose-response modelingt ools for nuclear receptors. The workshop will provide recommendations for further inquiry on these issues and the implications for health risk assessment.
Meeting Materials
For more information, contact Jacqueline Patterson (patterson@tera.org or 513-542-7475)