Validation of in vitro and in vivo methods for assessing endocrine disrupting chemicals.
The concepts that require validation in terms of the subject of endocrine disruption are listed and discussed. The main mechanisms by which endocrine disruption can occur are identified, and the assays required for the detection of adverse endocrine disruption toxicities associated with these mechanisms are discussed. The process of assay validation is considered. The validation of structure-activity relationships, the need for reference chemicals, and the problems recently encountered when attempting to reproduce endocrine disruption data are also explored. The most important conclusions derived from this analysis are that given the immature state of research into endocrine disruption toxicity, testing strategies and the types of assay employed should be kept under constant review; inevitably researchers need to accept the fact that future revision of each assay will be required. Second, given the current absence of any chemical that is universally accepted to be devoid of endocrine toxicity, assay specificity will be difficult to assess, and that imposes the need for alternative objective criteria for assessing the value of individual assays.
Ashby
J
J
Zeneca Central Toxicology Laboratory, Cheshire, United Kingdom. John.Ashby@CTL.Zeneca.com
D000818:Animals; D004703:Endocrine System / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006727:Hormone Antagonists / Q000633:toxicity*; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods*
D006727:Hormone Antagonists