OECD validation of phase 3 Hershberger assay in Korea using surgically castrated male rats with coded chemicals

✍ Scribed by Hyun-Ju Moon; Tae Seok Kang; Tae Sung Kim; Il Hyun Kang; Ho Youn Ki; Seung Hee Kim; Soon Young Han

• Book ID: 102294579
• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 99 KB
• Volume: 29
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.1418

✦ Synopsis

Abstract

As a participating laboratory for the OECD Hershberger validation program, we conducted a phase 3 trial to test the reliability of the Hershberger assay using coded substances. Male Sprague–Dawley rats were castrated at 6 weeks of age and allowed to recover for 8 days. All the coded substances were administered orally once daily for 10 consecutive days. In the antagonist version of the assay, 0.4 mg kg^−1^ of testosterone propionate (TP), a reference androgen, was co‐administered with the coded compounds C, D, H, I or K, by a subcutaneous injection. As anticipated, TP alone produced statistically significant increases in the five mandatory accessory sex organ weights. The coded substance L (trenbolone 40 mg kg^−1^), the test agonist, caused significant increases in the weights of the androgen‐dependent tissues. The five coded compounds, p,p′‐DDE at two doses (codes C and I), linuron at two doses (codes D and K) and flutamide (code H), all significantly decreased the weights of the TP‐stimulated sex organs. These results suggest the OECD Hershberger assay to be a reliable screening method for detecting androgen agonists and antagonists. Copyright © 2009 John Wiley & Sons, Ltd.