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John Ashby

Syngenta Central Toxicology Laboratory, Macclesfield, Cheshire, UK

Abstract

The gravimetric uterotrophic assay is currently the most well-established, short-term rodent estrogenicity assay. Increasing attention is being paid to the extent to which use of morphometric or molecular changes in the uterus could act as surrogates for the gravimetric end point of the assay, thereby perhaps increasing the sensitivity of the assay. In this paper I discuss the available data, paying particular attention to studies on bisphenol A (BPA) because it offers the largest database for consideration. I conclude that the case has yet to be made for augmenting the gravimetric end point of the uterotrophic assay. To resolve this important question, it will be necessary to conduct detailed dose-response studies where the no-observed-effect level (NOEL) for the proposed surrogate end points are compared with the NOEL for the gravimetric end point. Currently, few such studies exist, and among those that do no clear message emerges. The general trend to increasing use of molecular assays in toxicology (multigene microarrays and real-time polymerase chain reaction) emphasizes the need for clear criteria for comparing the performance of individual markers of toxicity. Key words: bisphenol A, lactoferrin, no-effect level, NOEL, surrogates for the uterotrophic assay. Environ Health Perspect 109:1091-1094 (2001) . [Online 10 October 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p1091-1094ashby/ abstract.html

Address correspondence to J. Ashby, Syngenta Central Toxicology Laboratory, Alderley Park, Cheshire, UK. Telephone: (44) 1 625 512833. Fax: (44) 1 625 590249. E-mail: John.Ashby@Syngenta.com

Received 5 March 2001 ; accepted 25 April 2001.