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Kanji Yamasaki,¹ Masakuni Sawaki,¹ Ryo Ohta,² Hirokazu Okuda,³ Seiichi Katayama,⁴ Tomoya Yamada,⁵ Takafumi Ohta,⁶ Tadashi Kosaka,⁷ and William Owens⁸

¹Chemicals Evaluation and Research Institute, Oita, Japan; ²Food Drug Safety Center, Kanagawa, Japan; ³Japan Bioassay Research Center, Kanagawa, Japan; ⁴Mitsubishi Chemical Safety Institute, Ibaraki, Japan; ⁵Sumitomo Chemical Company, Osaka, Japan; ⁶Panapham Laboratories Co., Ltd., Kumamoto, Japan; ⁷Institute of Environmental Toxicology, Ibaraki, Japan; ⁸Environmental Health and Safety Division, Organisation for Economic Co-operation and Development, Paris, France

Abstract
The Organisation for Economic Co-operation and Development has initiated the development of new guidelines for the screening and testing of potential endocrine disruptors. The Hershberger assay is one of the assays selected for validation based on the need for in vivo screening to detect androgen agonists or antagonists by measuring the response of five sex accessory organs and tissues of castrated juvenile male rats: the ventral prostate, the seminal vesicles with coagulating glands, the levator ani and bulbocavernosus muscle complex, the Cowper's glands, and the glans penis. The phase 1 feasibility demonstration stage of the Hershberger validation program has been successfully completed with a single androgen agonist and a single antagonist as reference substances. The phase 2 validation program employs a range of additional androgen agonists and antagonists as well as 5-reductase inhibitors. Seven Japanese laboratories have contributed phase 2 validation studies of the Hershberger assay using methyltestosterone, vinclozolin, and 2,2-bis (4-chlorophenyl) -1,1-dichloroethylene (p,p´-DDE) . The methyltestosterone doses were 0, 0.05, 0.5, 5, and 50 mg/kg/day, and the vinclozolin and p,p´-DDE doses were 0, 3, 10, 30, and 100 mg/kg/day. All chemicals were orally administered by gavage for 10 consecutive days. In the antagonist version of the assay using vinclozolin and p,p´-DDE, 0.2 mg/kg/day of testosterone propionate was coadministered by subcutaneous injection. All five accessory sex preproductive organs and tissues consistently responded with statistically significant changes in weight within a narrow window. Therefore, the Japanese studies support the Hershberger assay as a reliable and reproducible screening assay for the detection of androgen agonistic and antagonistic effects. Key words: Hershberger assay, methyltestosterone, OECD validation, p, p´-DDE, vinclozolin. Environ Health Perspect 111:1912-1919 (2003) . doi:10.1289/ehp.6357 available via http://dx.doi.org/ [Online 10 September 2003]

Address correspondence to K. Yamasaki, Chemicals Assessment Center, Chemicals Evaluation and Research Institute, 3-822, Ishii, Hita, Oita 087-0061, Japan. Telephone: 81-973-24-7211. Fax: 81-973-23-9800. E-mail: yamasaki-kanji@ceri.jp

This study was supported by grants from the Ministry of Economy, Trade, and Industry ; the Ministry of Health, Labour, and Welfare ; and the Ministry of the Environment in Japan.

The authors declare they have no competing financial interests.

Received 27 March 2003 ; accepted 10 September 2003.