home edit2 whole TSD November 2002 PDF format - OEHHA

Overall, the present epidemiological evidence suggests an association between chlorinated drinking
water consumption and human cancer, particularly bladder and gastrointestinal cancers. However,
these relationships cannot be directly correlated to chloroform exposure because many other
carcinogens are found in drinking water including other chlorinated halomethanes, brominated
halomethanes, industrial pollutants, and nonvolatile halogenated compounds.
Animal Studies
The National Cancer Institute conducted carcinogenesis bioassays of chloroform in both sexes of
Osborne-Mendel rats and B6C3F 1 mice (NCI, 1976). Mice and rats were given either corn oil or
chloroform in corn oil by gavage, 5 days/week for 78 weeks. Time-weighted average doses for female
rats were 100 and 200 mg/kg, and for male and female mice were 138 and 277 mg/kg, and 238 and
477 mg/kg, respectively. Tumor incidences are listed in Table 1.
A statistically significant increase (p < 0.05) in epithelial tumors of renal tubular origin was noted in the
treated males. Ten carcinomas, two of which had metastasized, and three adenomas of renal tubular
origin were found in 12 high dose male rats. In the low dose males, two carcinomas and two adenomas
of tubular origin were observed in four out of 50 animals. Among the 48 high dose female rats, one
tubular epithelial carcinoma and one renal squamous cell carcinoma were observed. No renal epithelial
tumors were noted in matched or colony controls. The NCI reported that these type of tumors rarely
occur spontaneously in Osborne-Mendel rats.
The incidence of thyroid tumors in female rats was statistically higher than controls in both treated
groups (p = 0.05, Fisher exact test) but not in treated male rats. The incidence of hepatocellular
carcinoma or neoplastic nodules was not increased in the chloroform-treated rats. Although
inflammatory pulmonary lesions occurred in all test groups, the lesions were more severe and occurred
more frequently in the chloroform-treated rats.
The incidence of hepatocellular carcinomas in mice was significantly elevated in all treatment groups (p <
0.001, Fisher exact test). The NCI reported that in their experience the spontaneous incidence of
hepatocellular carcinomas in B6C3F 1 mice is about 5-10% in males and 1% in females. The NCI
concluded that chloroform treatment was associated with increased incidences of hepatocellular
carcinomas in male and female mice and renal epithelial tumors in male rats.
In addition, Reuber (1979), based on his examination of the histological sections from the NCI study,
concluded that chloroform treatment was also associated with cancer of the liver in rats and an
increased incidence of malignant lymphomas in mice. However, the NCI did not agree with his findings.
The carcinogenicity of chloroform given in drinking water was evaluated in male Osborne-Mendel rats
and female B6C3F 1 mice (Jorgenson et al., 1985). The chloroform used (technical grade), was found
to contain 100 ppb diethylcarbonate, and trace amounts of 1,1-dichloroethane, dichloroethylene,
carbon tetrachloride, and an unidentified C 5 H 10 hydrocarbon. Time-weighted average doses of
chloroform calculated based on water consumption rates and body weight, ranged up to 160 and 263
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