Morphological and biochemical changes in the adult male rat reproductive system following long-term treatment with 1,2-dibromo-3-chloropropane.

Adult Long-Evans male rats were treated with various dosages of pure or technical grade 1,2-dibromo-3-chloropropane (DBCP), epichlorohydrin (Epi), or allyl chloride (AC) for 1, 3, or 6 months on a daily basis. AC, which is the substrate for the production of DBCP, and Epi, which is a contaminant and/or metabolite of DBCP, had no effect on any of the parameters of the male reproductive system studied. The deleterious effects on male reproduction are therefore attributable specifically to DBCP. The effects of DBCP were dose and duration dependent. At the lowest dose (1 mg/kg) DBCP did not have any discernible effects on the male reproductive system. By 3 months of treatment at the intermediate dose of 5 mg/kg, the morphology of the testis ranged from normally appearing seminiferous tubules to ones which contained Sertoli cells only. At 6 months of treatment there was a reduction in the weights of the testes and sexual accessory glands. At the highest dose, the majority of the rats showed advanced testicular regression by 1 month of treatment. The most extreme testicular regression was observed in the 6-month treatment group. Almost all of the seminiferous tubules of all of the rats were composed of Sertoli cells only. In some of the animals, a few isolated seminiferous tubules contained an occasional spermatogonium or primary spermatocyte. Some of the Leydig cells of the rats in this group showed morphological evidence of atrophy as evidenced by the clumping of chromatin and paucity of stainable cytoplasm. This was confirmed by lower levels of intratesticular testosterone, a significant reduction in the number of luteinizing hormone (LH) receptors and increased serum levels of LH and follicle-stimulating hormone (FSH). From these results we conclude that DBCP is a specific male gonadotoxin and that the effects are not a result of contamination or metabolism. The effects appear to be a direct action at the testicular level because feedback inhibition to the pituitary gland was adversely affected.