THE ANTISPERMATOGENIC EFFECT AND TOXICITY OF 2, 4-DINITRO-6-TERT BUTHYLPHENYL METHANESULFONATE ON SPRAGUE-DAWLEY RAT

Abstract

The antispermatogenic effects of 2, 4-dinitro-6-tert-. butylphenyl methanesulfonate (HE-166) were studied in Sprague-Dawley rats. They were fed 25, 100 and 400 ppm of HE-166 in the basal died for one year. Laboratory data showed no significant changes except for increases in γ-globulin, alkaline phosphatase, GOT and GPT values in the 100ppm group. Macroscopically, significant changes were found in the testes in the experimental group, which showed marked atrophy. Histologically, the testes were fined with fibrin exudate in the stroma and there was reduced spermatogonia, celluar debris and giant cells, and even calcification, depending on the dose of HE-166. The anti-fertility effects of HE-166 were also observed by mating rats and checking the pregnancy rate during three generations. These effects might be due to the direct cytotoxic effect of HE-166 on post-meiotic cells as epididymal spermatozoa and testicular sperm and spermatids. As far as tumor incidence was concerned, one case of fibroadenoma of the mammary gland, one case of leiomyosarcoma in the uterus in the 100 ppm group and one case of leiomyoma in the uterus in the 25 ppm group developed at around 8 months, but no other tumors developed.