The comparative effects of 1,2-dibromo-3-chloropropane (DBCP) and its metabolites, 3-chloro-1,2-propaneoxide (epichlorohydrin), 3-chloro-1,2-propanediol (alphachlorohydrin), and oxalic acid, on the urogenital system of male rats.
Reported similarities in the acute toxic effects of 1,2-dibromo-3-chloropropane (DBCP), 3-chloro-1,2-propaneoxide (epichlorohydrin, ECH), 3-chloro-1,2-propanediol (alphachlorohydrin, ACH), and oxalic acid (OA) have been suggested as presumptive evidence that the metabolism of DBCP to OA, via ECH and ACH, is the cause of the resulting injuries to the kidney and, perhaps, to the epididymis and testis. To test this hypothesis, the comparative toxicities of these four chemicals were studied in male rats after single subcutaneous (sc) injections of maximally tolerated (nonlethal) doses. Kidney, testicular, and liver functions were monitored, and the occurrences of morphological changes in these and several other organs were evaluated 24 hr, 3, 8, 25, and 75 days post-treatment. DBCP caused renal dysfunction (alterations in urine composition and reduced glomerular filtration rate) and marked necrosis of the proximal tubular epithelium in the outer medulla of the kidney. ACH and OA also elicited renal dysfunction, but ACH produced only a mild swelling of the proximal tubular epithelium in the renal cortex and OA produced a focal necrosis anatomically associated with crystal deposition. ECH caused a swelling of the proximal tubular epithelium in the renal cortex, but not frank kidney dysfunction. DBCP also caused a reversible vacuolization of the tubular epithelium in the caput epididymis, progressive testicular atrophy, and a reduction of cauda epididymal sperm concentration. ACH and ECH produced similar effects, as well as epididymal sperm granulomas, spermatocoeles, and an increase in the number of morphologically abnormal spermatozoa. OA failed to produce discernible epididymal or testicular lesions at any time during the study. The development of similar lesions in the epididymis and testis following DBCP, ECH, or ACH treatments is consistent with the theory of metabolism of these chemicals to a common causative gonadotoxic agent. Oxalic acid (OA), however, would not appear to be the common gonadal toxicant. Differences in the effects, both morphological and functional, of DBCP, ECH, ACH, and OA on the kidney, moreover, indicate that DBCP nephropathy is not mediated through metabolism to OA and suggest, as well, that it differs causally from that induced by ECH or ACH. Therefore, the metabolism of DBCP to ECH or ACH, and of ECH or ACH to OA, is insufficient to explain totally the toxic effects of these agents on the urogenital system in male rats.
D000818:Animals; D002728:Chlorohydrins / Q000633:toxicity*; D004811:Epichlorohydrin / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010070:Oxalates / Q000633:toxicity*; D019815:Oxalic Acid; D011188:Potassium / Q000652:urine; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000652:urine; D013094:Spermatozoa / Q000187:drug effects; D013270:Stomach / Q000187:drug effects; D013737:Testis / Q000473:pathology; D014566:Urogenital System / Q000187:drug effects*; D000517:alpha-Chlorohydrin / Q000633:toxicity*
D002728:Chlorohydrins; D010070:Oxalates; D004811:Epichlorohydrin; D000517:alpha-Chlorohydrin; C007318:1,2-dibromo-3-chloropropane; D019815:Oxalic Acid; D012964:Sodium; D011188:Potassium; D011407:Propane