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THE OECD PROGRAM TO VALIDATE THE RAT HERSHBERGER BIOASSAY TO SCREEN COMPOUNDS FOR IN VIVO ANDROGEN AND ANTIANDROGEN RESPONSES. PHASE 1: USE OF A POTENT AGONIST AND A POTENT ANTAGONIST TO TEST THE STANDARDIZED PROTOCOL
Citation:
OWENS, W., E. ZEIGER, M. WALKER, J. ASHBY, L. ONYON, AND L. E. GRAY. THE OECD PROGRAM TO VALIDATE THE RAT HERSHBERGER BIOASSAY TO SCREEN COMPOUNDS FOR IN VIVO ANDROGEN AND ANTIANDROGEN RESPONSES. PHASE 1: USE OF A POTENT AGONIST AND A POTENT ANTAGONIST TO TEST THE STANDARDIZED PROTOCOL. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 114(8):1259-1265, (2006).
Impact/Purpose:
To use the Rat Hershberger Bioassay to Screen Compounds for in Vivo Androgen and Antiandrogen Responses
Description:
The OECD has completed Phase-1 of the Hershberger validation intended to identify in vivo activity of
suspected androgens and antiandrogens. 17 laboratories from 7 countries participated in Phase-1, and results
were collated and evaluated by the OECD with the support of an international committee of experts. Five
androgen-responsive tissues (ventral prostate, paired seminal vesicles and coagulating glands, levator ani and
bulbocavernosus muscles, glans penis, and paired Cowper's or bulbourethral glands) were evaluated. The
standardized protocols used selected doses of a reference androgen, testosterone propionate (TP), and
antiandrogen, Flutamide (FLU). All laboratories successfully detected androgen-responsive tissue weight
increases using TP, and decreases in TP stimulated tissue weights when FLU was coadministered. The
standardized protocols performed well under a variety of conditions (e.g., strain, diet, housing protocol, bedding,
etc.). There was good agreement among laboratories with regard to the TP doses inducing significant increases
in tissue weights and to the FLU doses decreasing TP-stimulated tissue weights. Several additional procedures
(e.g., weighing of the dorso-lateral prostate and fixation of tissues before weighing) and serum component
measurements (e.g., luteinizing hormone) were also included by some laboratories to assess their potential
utility. The results indicated that the OECD Hershberger protocol was robust, reproducible, and transferable
across laboratories. Based on this Phase-1 validation study, the protocols have been refined and the next phase
of the OECD validation program will test the protocol with selected doses of weak androgen agonists, androgen
antagonists, a 5¿-reductase inhibitor, and chemicals having no androgenic activity.