Assessment in rats of the gonadotoxic and hepatorenal toxic potential of dibromochloropropane (DBCP) in drinking water.
This investigation was undertaken to assess the potential of ingested 1,2-dibromo-3-chloropropane (DBCP) to cause testicular and hepatorenal injury, in light of the paucity of data applicable to risk assessment of DBCP in drinking water. Adult male Sprague-Dawley rats were supplied ad libitum with water containing 0, 5, 50, 100, and 200 ppm DBCP for 64 days. A dose-related decrease in water consumption occurred during the study. The 200-ppm animals drank less than half as much water as controls, consumed less food, and subsequently exhibited significantly lower body weight gain. DBCP ingestion thus was not directly proportional to the level of chemical in the water, although daily and cumulative intake of DCP were concentration dependent. Average daily intake of DBCP for the 64-day exposure period was as follows: 5 ppm = 0.4 mg/kg/day; 50 ppm = 3.3 mg/kg/day; 100 ppm = 5.4 mg/kg/day; 200 ppm = 9.7 mg/kg/day. Blood samples were taken after 2, 4, and 6 weeks of exposure and at the terminal sacrifice and assayed for serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sorbitol dehydrogenase, and ornithine-carbamyl transferase activities and BUN levels. No evidence of liver damage at any exposure level was indicated by either the clinical chemistry indices or histopathology. Histologic examination revealed an apparent increase in the number of nuclei per renal proximal tubule cross-section in the 200-ppm group, possibly indicative of an increased turnover of proximal tubular cells. A slight, but statistically significant, decrease in absolute testicular weight was manifest in the 200-ppm animals, although the decrease was not significant when testicular weight was calculated as g/100 g body wt. Epididymal sperm counts and serum luteinizing hormone, follicle stimulating hormone, and intratesticular testosterone levels were not altered by any dose of DBCP. A qualitative histopathological examination of the testicular seminiferous epithelium failed to reveal any abnormalities in the spermatogenic process.
Heindel
J J
JJ
National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina 27709.
Berkowitz
A S
AS
Kyle
G
G
Luthra
R
R
Bruckner
J V
JV
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004700:Endocrine System Diseases / Q000139:chemically induced*; D004798:Enzymes / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011407:Propane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000187:drug effects*
D004798:Enzymes; D012739:Gonadal Steroid Hormones; D007306:Insecticides; C007318:1,2-dibromo-3-chloropropane; D011407:Propane