1,2-dibromo-3-chloropropane (DBCP)-induced infertility in male rats mediated by a post-testicular effect

The potential for the chemosterilant 1,2-dibromo-3-chloropropane (DBCP) to reduce male fertility by acting at a site in the genital tract beyond the testis was evaluated in male, Fischer 344 rats. A single sc treatment with 100 mg/kg DBCP reduced fertility in male rats 2 to 7 days postexposure without affecting mating frequency. Doses of 10, 20, or 40 mg/kg DBCP given sc once daily for 7 days caused a dose-dependent reduction in the metabolism of glucose to CO2 by epididymal sperm, as measured in vitro. Conversion of glucose to lactate was not reduced, indicating inhibition of energy metabolism at a step post-glycolysis. No clinical signs of toxicity were observed in these studies. Direct addition of DBCP to epididymal sperm being incubated in vitro also inhibited the metabolism of glucose to CO2. Inhibition was concentration related, and the minimal inhibitory concentration was 0.316 mM. These data indicate that DBCP may cause a nearly immediate infertility via a direct effect on post-testicular sperm. A possible mechanism of this infertility is inhibition by DBCP of glucose metabolism in the ejaculated sperm.