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HESI PROJECT COMMITTEE ON DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY

This project committee focuses on studying dose-dependent transitions in mechanisms of toxicity. They aim to build consensus on principles and applications through case examples and outreach initiatives.

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HESI PROJECT COMMITTEE ON DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY

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  1. HESI PROJECT COMMITTEE ONDOSE-DEPENDENT TRANSITIONSIN MECHANISMS OF TOXICITY NANCY G. DOERRER, MS HESI ndoerrer@ilsi.org SOT Risk Assessment Specialty Section Teleconference February 9, 2005

  2. Project Committee Leadership Chair: DR. WILLIAM SLIKKER, JR. US Food and Drug Administration National Center for Toxicological Research Vice Chair / Scientific Advisor: DR. KENDALL WALLACE University of Minnesota

  3. Project History • 2001: Project Committee formed; objectives defined • 2002: Development of case examples to demonstrate dose-dependent transitions • 2003: Multi-stakeholder, multi-sector workshop to build consensus on principles and applications • 2004: TAAP publications • 2003-2005: Outreach

  4. Project Committee Participation Government Participation:Agency for Toxic Substances and Disease Registry, National Institute of Environmental Health Sciences, US Environmental Protection Agency, US Food and Drug Administration Academic Participation:Clark University, University of Kansas Medical Center, University of Minnesota, University of North Carolina Industry:The Dow Chemical Company, DuPont Haskell Laboratory for Health and Environmental Sciences, Eastman Kodak Company Other Participants:CIIT Centers for Health Research, Gaylor and Associates, LLC, ILSI RSI

  5. February 12-13, 2003, WorkshopWashington, DC • Co-Sponsors: HESI, ATSDR, ACC, NIEHS, SOT, and US EPA, with additional support from Health Canada • Purpose: to examine approaches to dose-response analysis, learn from the case study examples, and gather feedback on the impact of dose-dependent transitions on the risk assessment process. • Participation: approximately 50 invited scientists from government, academia, and industry

  6. Melvin Andersen (CIIT) Matthew Bogdanffy (DuPont) James Bus (Dow) Rory Conolly (CIIT) Raymond David (Kodak) Christopher DeRosa (ATSDR) Nancy Doerrer (HESI) John Doull (University of Kansas) William Farland (EPA) Penelope Fenner-Crisp (ILSI RSI) David Gaylor (Gaylor and Associates) Dale Hattis (Clark University) Gary Kimmel (EPA) Christopher Portier (NIEHS) Bernard Schwetz (FDA) R. Woodrow Setzer, Jr. (EPA) William Slikker, Jr. (FDA) Bob Sonawane (EPA) James Swenberg (University of NC) Kendall Wallace (University of MN) Mildred Williams-Johnson (ATSDR) Workshop Organizing Committee

  7. Publications Slikker, W., Jr., Andersen, M.E., Bogdanffy, M.S., Bus, J.S., Cohen, S.D., Conolly, R.B., David, R.M., Doerrer, N.G., Dorman, D.C., Gaylor, D.W., Hattis, D., Rogers, J.M., Setzer, R.W., Swenberg, J.A., Wallace, K., 2004a. Dose-dependent transitions in mechanisms of toxicity. Toxicol. Appl. Pharmacol. 201, 203-225. Slikker, W., Jr., Andersen, M.E., Bogdanffy, M.S., Bus, J.S., Cohen, S.D., Conolly, R.B., David, R.M., Doerrer, N.G., Dorman, D.C., Gaylor, D.W., Hattis, D., Rogers, J.M., Setzer, R.W., Swenberg, J.A., Wallace, K., 2004b. Dose-dependent transitions in mechanisms of toxicity: case studies. Toxicol. Appl. Pharmacol. 201, 226-294

  8. Outreach 2003: • Workshop, Society of Toxicology Annual Meeting, Salt Lake City, UT 2005: • February SOT/RASS Monthly Teleconference • SOT/RASS Meeting, March Annual Meeting • Poster, May FDA Science Forum • Poster, May EPA Science Forum • Session, November Annual Meeting of the American College of Toxicology, Williamsburg, VA

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