Use of quantitative testicular histology to assess the effect of dibromocholoropropane (DBCP) on reproduction in rabbits

Abstract

Dibromochloropropane (DBCP) was administered orally to 36 sexually mature male Dutch Belted rabbits assigned at random to one of six groups to receive 0, 0.94, 1.88, 3.75, 7.5, or 15.0 mg DBCP per kilogram of body weight daily 5 days per week during a 69-day treatment period. Animals were euthanized and necropsied on Day 70. Body weights and weights of the kidneys, liver, epididymides, and accessory sex glands were not influenced by DBCP treatment. The highest dosage reduced mean paired testes weight to 45% of control values ( p < 0.01). Mean seminiferous tubular diameter was reduced by 15 and 29% with the two highest dosages of DBCP, respectively ( p < 0.01), and the percentage of seminiferous tubules containing elongating and round spermatids, as the most advanced cell type present, was decreased ( p < 0.01). The number of leptotene primary spermatocytes per Sertoli cell, and the numbers of spermatogonia, young and old primary spermatocytes, and Step 1 spermatids per Stage I seminiferous tubular cross section likewise indicated a general depression ( p < 0.01) of spermatogenesis. Based upon the number of Step 1 spermatids per cross section at Day 70, production of sperm at this time by rabbits receiving the highest dose of DBCP was estimated to be less than one-fourth of control values. No significant effect ( p > 0.05) of 0.94 mg DCBP/kg on any parameters was found, so this could be considered to be the no effect dose. However, the regressions and mean values are interpreted to indicate that the no effect level of DBCP may be less than 0.94 mg DBCP/kg of body weight. It is suggested that the most sensitive tests described here be included in future screening tests for potential effects of agents on male reproduction.