Identification and assessment of endocrine disruptors: limitations of in vivo and in vitro assays.
It has been suggested that chemicals and complex mixtures capable of modulating the endocrine system may contribute to adverse health, reproduction, and developmental effects in humans and wildlife. These effects include increased incidence of hormone-dependent cancers, compromised reproductive fitness, and abnormal reproductive system development. In response to public concern, regulatory agencies in North America and Europe are formulating potential strategies to systematically test chemicals and complex mixtures for their endocrine-disrupting activities. Because of the complexity of the endocrine system and the number of potential endocrine disruptor targets, a tiered approach involving a complementary battery of short- and long-term in vivo and in vitro assays that assesses both receptor and nonreceptor-mediated mechanisms of action is being considered. However, the available established assays use a limited number of end points, and significant information gaps exist for other potential targets in the endocrine system. In addition to discussing the merits and limitations of the assays that may be adopted, this paper also highlights potential problems associated with the use of a tiered testing strategy.
Zacharewski
T
T
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada. tzachare@pilot.msu.edu
D000818:Animals; D002478:Cells, Cultured; D004703:Endocrine System / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D011237:Predictive Value of Tests; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods*; D015262:Xenobiotics / Q000494:pharmacology / Q000633:toxicity*
D015262:Xenobiotics