You are here:
CARCINOGENICITY OF BROMODICHLOROMETHANE ADMINISTERED IN DRINKING WATER TO MALE F344/N RATS AND B6C3F1 MICE
Citation:
George, M H., G. R. Olson, D Doerfler, T. Moore, S. Kilburn, AND A B. DeAngelo. CARCINOGENICITY OF BROMODICHLOROMETHANE ADMINISTERED IN DRINKING WATER TO MALE F344/N RATS AND B6C3F1 MICE. INTERNATIONAL JOURNAL OF TOXICOLOGY 21(3):219-230, (2001).
Description:
A life-time exposure study was conducted to assess the carcinogenicity of bromodichloromethane (BDCM) administered in the drinking water to male F344/N rats and B6C3F1 mice. Mouse: Target concentrations of BDCM (dissolved in deionized water containing 0.25% emulphor) were 0.05, 0.25, and 0.50 g/L. The calculated mean daily BDCM concentrations (measured concentrations corrected for on-cage loss of chemical) were 0.06, 0.28 and 0.49 g/L. Water consumption in the 0.28 and 0.49 g/L treatment groups was significantly depressed to 83% and 77% of the control value. Time-weighted water consumption of 135, 97, and 89 ml/kg/day resulted in mean daily doses (MDD) of 8.1, 27.2, and 43.4 mg BDCM/kg/day over 104 weeks. No changes in feed consumption, final body weight, or survival were observed for any BDCM treatment. Kidney weights were significantly depressed in the 27.2 and 43.4 mg/kg/day treatment groups. Liver, kidney, spleen, testis, bladder, sections along the alimentary tract, and all excised lesions were examined for histopathology. There was no increase in the prevalence of neoplasia in the kidney or at any other organ site. Rat: The target BDCM concentrations were 0.07, 0.35, and 0.70 g/L; the mean daily BDCM concentrations corrected for chemical loss were 0.06, 0.33, and 0.62 g/L. No alterations in water or feed consumption, body weight gain, and survival were measured for any of the BDCM treatments. Time-weighted water consumption of 65, 63, and 59 ml/kg/day yielded MDDs of 3.9, 20.6 and 36.3 mg BDCM/kg/day. Kidney weight was significantly depressed in the 36.3 mg/kg/day treatment group. There was a significantly enhanced prevalence and multiplicity of hepatocellular adenomas (HA) in the 3.9 mg/kg/day dose group (15.5% and 0.16 HA/animal vs 2.2% and 0.02 HA/animal for the control group). The prevalence and multiplicity of hepatocellular carcinomas (HC) increased from 2.2% and 0.02 HC/animal for the control and 3.9 mg/kg/day groups to 8.3% and 0.10 HC/animal in the 20.6 mg/kg/day treatment group. The combined neoplasms (HA + HC) were enhanced at 3.9 abd 20.6 mg BDCM/kg/day. The prevalence and mutiplicity of hepatocellular neoplasia were depressed to the control levels in the 36.3 mg BDCM/kg treatment group. There was an inverse relationship between the prevalence of basophilic and clear cell altered foci of cells (AFC) and BDCM dose. The frequency of eosinophilic AFC was not affected by BDCM treatment. BDCM did not increase the prevalence or multiplicity of neoplasia in the large bowel, renal tubules or in any of the other tissues examined. An increased prevalence of renal tubular hyperplasia was observed in the high dose group (15.8% vs 8.7% for the control group). It was concluded that under the conditions of this study, BDCM administered in the drinking water was not carcinogenic in the male B6C3F1 mouse, but was carcinogenic in the male F344/N rat based on the increased prevalence and multiplicity of hepatocellular neoplasia in the 3.9 and 20.6 mg BDCM/kg/day treatment groups.