Predicting health effects of exposures to compounds with estrogenic activity: methodological issues

Environmental Health Perspectives
R Rudel

Abstract

Many substances are active in in vitro tests for estrogenic activity, but data from multigenerational and other toxicity studies are not available for many of those substances. Controversy has arisen, therefore, concerning the likelihood of adverse health effects. Based on a toxic equivalence factor risk assessment approach, some researchers have concluded that exposure to environmental estrogens is not associated with estrogen receptor (ER)-mediated health effects. Their rationale cites the low potency of these compounds in in vitro assays relative to estradiol, and the widespread exposure to pharmaceutical, endogenous, and dietary estrogens. This reasoning relies on two assumptions: that the relative estrogenic potency in in vitro assays is predictive of the relative potency for the most sensitive in vivo estrogenic effect; and that all estrogens act via the same mechanism to produce the most sensitive in vivo estrogenic effect. Experimental data reviewed here suggest that these assumptions may be inappropriate because diversity in both mechanism and effect exists for estrogenic compounds. Examples include variations in ER-ligand binding to estrogen response elements, time course of nuclear ER accumulation, patterns of gene a...Continue Reading

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Citations

Mar 17, 2001·Environmental Health Perspectives·P L Whitten, H B Patisaul
Jun 27, 2003·Environmental Health Perspectives·Julia Green Brody, Ruthann A Rudel
Jun 8, 2002·Toxicology Letters·Gisela H DegenHermann M Bolt
Jul 16, 2014·Regulatory Toxicology and Pharmacology : RTP·Tzutzuy RamirezBennard van Ravenzwaay

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