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Melvin E. Andersen,¹Rory B. Conolly,² Elaine M. Faustman,³ Robert J. Kavlock,⁴ Christopher J. Portier,⁵ Daniel M. Sheehan,⁶ Patrick J. Wier,⁷ and Lauren Ziese⁸

¹Department of Environmental Health, Colorado State University, Fort Collins, Colorado USA;
²Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina USA;
³Department of Environmental Health, University of Washington, Seattle, Washington USA;
⁴National Health and Environmental Effects Research Laboratories, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina USA;
⁵National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina USA;
⁶National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas USA;
⁷SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania USA;
⁸California Protection Agency, RCHAS/Office of Environmental Health Hazard Association, Berkeley, California USA

Abstract

A wide range of toxicity test methods is used or is being developed for assessing the impact of endocrine-active compounds (EACs) on human health. Interpretation of these data and their quantitative use in human and ecologic risk assessment will be enhanced by the availability of mechanistically based dose-response (MBDR) models to assist low-dose, interspecies, and in vitro to in vivo extrapolations. A quantitative dose-response modeling work group examined the state of the art for developing MBDR models for EACs and the near-term needs to develop, validate, and apply these models for risk assessments. Major aspects of this report relate to current status of these models, the objectives/goals in MBDR model development for EACs, low-dose extrapolation issues, regulatory inertia impeding acceptance of these approaches, and resource/data needs to accelerate model development and model acceptance by the research and the regulatory community. Key words: endocrine-active compounds, endocrine disruptors, linkage models mechanistic dose-response modeling, pharmacodynamics, pharmacokinetics, risk assessment extrapolations. -- Environ Health Perspect 107(suppl 4) :631-638 (1999) .

http://ehpnet1.niehs.nih.gov/docs/1999/suppl-4/631-638andersen/abstract.html