TOXIC EFFECTS OF 1,2-DIBROMO-3-CHLOROPROPANE ON THE UROGENITAL SYSTEM

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1,2-Dibromo-3-chloropropane (DBCP) produces a rapid decrease in male fertility in laboratory animals after acute exposure. Studies were performed to determine the biochemical basis for this effect. Treatment of rats with DBCP for seven days caused a decrease in the metabolism of glucose to CO2 in isoplated sperm, with a concomitant increase in lactate accumulation. These results indicate that DBCP may inhibit sperm carbohydrate metabolism at a site post-glycolysis. DBCP similarly inhibited the metabolism of a variety of tricarboxylic acid cycle intermediates to C02 in epididymal sperm isolated from Fischer 344 rats. DBCP did not inhibit the activities of NAD-dependent dehydrogenase enzymes in glycolysis or the tricarboxylic acid cycle; however, it did inhibit the rates of oxygen consumption from endogenous substrates and NAD-linked tricarboxylic intermediates. Oxidation of succinate, an FAD-linked substrate, was insensitive to DBCP. It is concluded that DBCP inhibits sperm carbohydrate metabolism at the NADH dehydrogenase step in the mitochondrial electron transport chain. Inhibition of carbohydrate metabolism by DBCP was attributed to the parent compound, since all effects were immediate and linear with time. The rapid infertility caused by exposure to DBCP may be a result of cellular ATP levels being less than that which is required for motility or penetration of the ovum by the sperm.