Evaluation of the rodent Hershberger assay using three reference endocrine disrupters (androgen and antiandrogens)

Abstract

Three chemicals with known endocrine activities have been evaluated in the rat Hershberger assay for phase-2 of the international validation exercise within the Organization for Economic Cooperation and Development (OECD). The chemicals studied included the antiandrogens finasteride (FIN) and procymidone (PRO) and the androgen agonist 17α-methyltestosterone (MT). Castration of sexually immature Sprague–Dawley rats was performed between post-natal days 42 and 46 whilst dosing of the chemical over 10 days was performed between post-natal days 53 and 67. Rats were co-treated with testosterone propionate (TP) for the antiandrogenic activity evaluation. The endpoints examined for evaluation of the androgenic/antiandrogenic activity were changes in sex accessory tissue (SAT) weights supplemented with measurement of testosterone and luteinizing hormone (LH) levels at sacrifice. Changes in liver, adrenal, kidney and body weights were also monitored for general toxicity assessment. Statistically significant changes in the SAT weights were detected with the three chemicals tested. Hence, the rat Hershberger assay as defined by the OECD was demonstrated sensitive enough for the detection of the endocrine disrupting activity of the three reference chemicals evaluated.