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OBJECTIVE: The Organisation for Economic Co-operation and Development (OECD) has completed phase 2 of an international program to validate the rodent Hershberger bioassay.
DESIGN: The Hershberger bioassay is designed to identify suspected androgens and antiandrogens based on changes in the weights of five androgen-responsive tissues (ventral prostate, paired seminal vesicles and coagulating glands, the levator ani and bulbocavernosus muscles, the glans penis, and paired Cowper's or bulbourethral glands). Protocol sensitivity and reproducibility were tested using two androgen agonists (17α-methyl testosterone and 17β-trenbolone), four antagonists [procymidone, vinclozolin, linuron, and 1,1-dichoro-2,2-bis-(p-chlorophenyl)ethylene (p,p'-DDE)], and a 5α-reductase inhibitor (finasteride). Sixteen laboratories from seven countries participated in phase 2.
RESULTS: In 40 of 41 studies, the laboratories successfully detected substance-related weight changes in one or more tissues. The one exception was with the weakest antiandrogen, linuron, in a laboratory with reduced sensitivity because of high coefficients of variation in all tissue weights. The protocols performed well under different experimental conditions (e.g., strain, diet, housing protocol, bedding, vehicle). There was good agreement and reproducibility among laboratories with regard to the lowest dose inducing significant effects on tissue weights.
CONCLUSIONS: The results show that the OECD Hershberger bioassay protocol is reproducible and transferable across laboratories with androgen agonists, weak androgen antagonists, and a 5α-reductase inhibitor. The next validation phase will employ coded test substances, including positive substances and negative substances having no androgenic or antiandrogenic activity.
KEY WORDS: androgen, antiandrogen, bulbocavernosus, Cowper's glands, DDE, endocrine disruption, Finasteride, glans penis, Hershberger, levator ani, seminal vesicles, linuron, methyl testosterone, procymidone, trenbolone, validation, ventral prostate, vinclozolin. Environ Health Perspect 115:671-678 (2007). doi:10.1289/ehp.9666 available via http://dx.doi.org [Online 17 January 2007]
The Organisation for Economic Co-operation and Development (OECD) undertook the revision of existing guidelines and development of new guidelines for screening and testing of potential endocrine disruptors in 1997 (OECD 1998). Validation of new guidelines is managed by a Validation Management Group (VMG). One VMG program is the rodent Hershberger bioassay, which is intended to be used as a screen for suspected androgen agonists and antagonists, and to assist in compound prioritization for further evaluation. In the Hershberger program phase 1, standardized protocols were developed and successfully tested against the high-potency reference androgen testosterone propionate (TP) and die antiandrogen flutamide (FLU). The protocols were...