Natural and anthropogenic environmental oestrogens:
the scientific basis for risk assessment

Issues associated with the validation of in vitro and in vivo methods for assessing endocrine disrupting chemicals

J. Ashby
Zeneca Central Toxicology Laboratory, Alderley Park, Cheshire SK10 4TJ, UK.

Abstract: The concepts requiring validation in 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 within the context of the criteria established by Balls and Karcher. 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 to derive from this analysis are first, 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, with the inevitable need for future revision of each being accepted from the outset. Second, that given the current absence of any chemical universally accepted as being devoid of endocrine toxicity, assay specificity will be impossible to assess, and that imposes the need for alternative objective criteria for assessing the value of individual assays.

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