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CARCINOGENICITY OF BROMODICHLOROMETHANE ADMINISTERED IN DRINKING WATER TO THE MALE F344/N RAT AND B6C3F, MOUSE
Citation:
George, M H., T. M. Moore, S. R. Kilburn, D L. Doerfler, AND A B. DeAngelo. CARCINOGENICITY OF BROMODICHLOROMETHANE ADMINISTERED IN DRINKING WATER TO THE MALE F344/N RAT AND B6C3F, MOUSE. Presented at American Water Works Association Microbial/Disinfection By-Products Effects Symposium, Lisle, IL, March 24-26, 2001.
Description:
CARCINOGENICITY OF BROMODICHLOROMETHANE ADMINISTERED IN DRINKING WATER TO THE MALE F344/N RAT AND B6C3F1 MOUSE.
Bromodichloromethane (BDCM) has been shown to produce kidney and large bowel tumors in both male and female F344/N rats, kidney tumors in male B6C3F 1 mice and liver tumors in female B6C3F 1 mice when administered by daily gavage in corn oil (National Toxicology Program, 1987). Since the trihalomehanes are an important class of chlorine disinfection by-product found in finished drinking waters, we initiated a study to assess the carcinogenicity of BDCM administered to rodents in the drinking water containing 0.25% emulphor for 2 years. Rats: Measured BDCM drinking water concentrations for the study were 0.06, 0.33 and 0.62 g/L BDCM which yielded time-weighted mean daily doses (MODs) of 3.9, 20.6, 36.3mg
/kg/day. Water consumption, survival, body weight, and organ weight were not altered by any BDCM treatment. Increased prevalence (percent of animals with a tumor) of hepatocellular adenoma was seen only for the lowest dose: control, 0%; 3.9 mg/kg/day, 15.6% (p< 0.05); 20.6 mg/kg/day, 6.3%; and 36.3 mg/kg/day, 4.1 %. Neither the prevalence nor multiplicity (tumors/animal) of hepatocellular carcinoma was altered. Hepatocellular hyperplasia was evident in all dose groups, but only significant at 20.6 and 36.3 mg/kg/day. BDCM enhanced renal tubular hyperplasia which was statistically significant in the low and high doses (p< 0.05). BDCM did not alter the incidence of tumors in the kidney and large intestine. Mice: Measured BDCM drinking water concentrations were 0.06,0.25, and 0.50 g/1 which yielded MDDs of 6.1,24.5, and 41.3 mg/kg/day. Water consumption, survival, body and organ weights were not altered by any of the BDCM treatments. Life-time exposures to BDCM failed to increase the prevalence orthe multiplicity of hepatocellular neoplasia in mice. Enhanced neoplasia was not observed in the liver, kidney, large bowel, or any other tissue examined. Rats and Mice: Hepatocellular necrosis in BDCM treated rodents was minimal and did not exceed that in untreated animals. BDCM did not alter serum chemistry or hepatocyte proliferation at any of the time periods monitored. However, there was a significant dose related decrease in the hepatocyte labeling index in the rat after 26 and 78 weeks of exposure. Summary: BDCM administered in the drinking water to male rats and mice did not increase the prevalence of kidney or large intestine cancer in rats or the prevalence of kidney neoplasia in male mice as had been reported for BDCM administered by corn oil gavage. An increased prevalence of benign hepatocellular lesions was observed in the rat only at the lowest BDCM concentration without the demonstration of a dose-response. We conclude that under the conditions of the bioassay BOCM was not carcinogenic in male mice and rats.
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