Quantitative mechanistically based dose-response modeling with endocrine-active compounds.
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 (italic)in vitro(/italic) to (italic)in vivo(/italic) 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.
Andersen
M E
ME
Department of Environmental Health, Colorado State University, Fort Collins, Colorado 80523, USA. andersenme@aol.com
Conolly
R B
RB
Faustman
E M
EM
Kavlock
R J
RJ
Portier
C J
CJ
Sheehan
D M
DM
Wier
P J
PJ
Ziese
L
L
D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects* / Q000502:physiology; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D008962:Models, Theoretical; D018570:Risk Assessment / Q000379:methods; D015262:Xenobiotics / Q000009:adverse effects* / Q000494:pharmacology
D004785:Environmental Pollutants; D015262:Xenobiotics