Preliminary evaluation of the major protocol variables for the Hershberger castrated male rat assay for the detection of androgens, antiandrogens, and metabolic modulators

A review of the many test protocols employed for the Hershberger castrated male rat assay is presented. The critical protocol variables thereby defined have been evaluated experimentally. Strong antiandrogens inhibit the regrowth of sex accessory tissues in all experiments, regardless of the protocol used. Thus, age of rat at castration, dose of testosterone used, and duration of the treatment had little effect on the activities observed with agents such as flutamide and vinclozolin. In contrast, other chemicals, such as DDE and DBP, were only active under specific conditions of test. It is concluded that the Hershberger assay appears to be a sensitive and practical test system for the detection of androgens, antiandrogens, and inhibitors of male sex hormone anabolism. However, continued attention will need to be given to the derivation of a standard protocol for the routine deployment of the assay. The present results, taken together with those of the current OECD evaluation of this assay, should lead rapidly to such an agreed test protocol. The status of the Hershberger assay in relation to the intact peripubertal male rat assay is discussed, and it is concluded that comparison of the relative merits of these two assays must await the derivation of a larger database. (C) 2000 Academic Press.