Evaluation of the rodent Hershberger bioassay using three reference (anti)androgens

Under the umbrella of the Organization for Economic Cooperation and Development (OECD) the rodent Hershberger bioassay is being validated as an in vivo screen for the detection of (anti)androgens. As part of the validation work we studied trenbolone (TREN), 1,1-bis-(4-chlorophenyl)-2,2-dichloroethylene (p,p'-DDE) and vinclozolin (VIN). Oral intubation of castrated rats with TREN [0.3-1.5-8-40 mg kg(-1) body weight (b.w.)] for ten days increased androgen-sensitive tissue weights (ASTW) at the high dose. p,p'-DDE (5-16-50-160 mg kg(-1) b.w.) and VIN (0-3-10-30-100 mg kg(-1) b.w.) orally administered for ten days produced a dose-dependent decrease in ASTW in castrated rats subcutaneously supplemented with testosterone propionate (0.4 mg kg(-1) b.w.). p,p'-DDE also strongly increased liver weights and induced hepatocellular hypertrophy and thyroid follicular cell hypertrophy that was most likely mediated by liver enzyme induction. Our data strongly suggest that the OECD protocol of the rodent Hershberger bioassay describes a sensitive in vivo screen, capable of detecting weakly active (anti)androgens. Furthermore, our data may also indicate that thyroid effects could be assessed, if the protocol is amended accordingly.