- Full (HTML) - Full (PDF) - Related EHP Articles - PubMed:Related Articles - PubMed:Citation - Cited in PMC - Purchase This Issue

Jun Kanno,¹ Lesley Onyon,² Shyamal Peddada,³ John Ashby,⁴ Elard Jacob,⁵ and William Owens⁶

¹National Institute of Health Sciences, Tokyo, Japan; ²Environmental Health and Safety Division, Organisation for Economic Co-operation and Development, Paris, France; ³National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA; ⁴Syngenta Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom; ⁵BASF Aktiengesellschaft, Ludwigshafen, Germany; ⁶The Procter & Gamble Company, Cincinnati, Ohio, USA

Abstract
The Organisation for Economic Co-operation and Development has completed phase 2 of an international validation program for the rodent uterotrophic bioassay. This portion of phase 2 assessed the reproducibility of the assay with a battery of positive and negative test substances. Positive agonists of the estrogen receptor included the potent reference estrogen 17-ethinyl estradiol (EE) , and the weak estrogen agonists bisphenol A, genistein, methoxychlor, nonylphenol, and o,p´-DDT. The negative test substance or nonagonist was n-dibutylphthalate. The test substances were coded, and prescribed doses of each test substance were administered in 16 laboratories. Two versions of the uterotrophic assay, the intact immature and the adult ovariectomized female rat, were tested and compared using four standardized protocols covering both sc and po administration. Assay reproducibility was compared using a) EE doses identical to those used in phase 1 and in parallel dose-response studies, b) single doses of the weak agonists identical to one of five doses from the dose-response studies, and c) a single dose of the negative test substance. The results were reproducible and in agreement both within individual laboratories and across the participating laboratories for the same test substance and protocol. The few exceptions are examined in detail. The reproducibility was achieved despite a variety of different experimental conditions (e.g., variations in animal strain, diet, housing protocol, bedding, vehicle, animal age) . In conclusion, both versions of the uterotrophic bioassay and all protocols appear robust, reproducible, and transferable across laboratories and able to detect weak estrogen agonists. These results will be submitted along with other data for independent peer review to provide support for the validation of the uterotrophic bioassay. Key words: endocrine disruption, estrogen, rat uterus, uterotrophic. Environ Health Perspect 111:1550-1558 (2003) . doi:10.1289/ehp.5870 available via http://dx.doi.org/ [Online 23 January 2003]