title: Report on the Carcinogenesis Bioassay of Chloroform (CAS No. 67-66-3).
abstract: Chloroform, also known as trichloromethane, is primarily used (93%) in the manufacture of fluorocarbons for refrigerants, propellants, and plastics. The remainder is used for many purposes including extracting and purifying antibiotics, as an industrial solvent, in preparation of dyes, drugs and pesticides, as a component of some toothpastes, cough medicines, liniments, salves, in photographic processing and in industrial drycleaning. A carcinogenesis bioassay of USP grade chloroform was conducted using Osborne-Mendel rats and B6C3F1 mice. Chloroform was administered orally (by gavage) in corn oil to 50 animals of each sex and at two dose levels five times per week for 78 weeks. Rats were started on test at 52 days of age and sacrificed after 111 weeks. The dose levels for males were 90 and 180 mg/kg body weight. Female rats were started at 125 and 250 mg/kg, reduced to 90 and 180 mg/kg after 22 weeks, with an average level of 100 and 200 mg/kg for the study. A decrease in survival rate and weight gain was evident for all treated groups. The most significant observation (P=.0016) was kidney epithelial tumors in male rats with incidences of: 0% in controls, 8% in the low dose and 24% in the high dose groups. Although an increase in thyroid tumors was also observed in treated female rats, this finding was not considered biologically significant. Mice were started on test at 35 days and sacrificed after 92-93 weeks. Initial dose levels were 100 and 200 mg/kg for males and 200 and 400 mg/kg or female mice. These levels were increased after 18 weeks to 150/300 and 250/500 mg/kg respectively so that the average levels were 138 and 277 mg/kg for males and 238 and 477 mg/kg for female mice. Survival rates and weight gains were comparable for all groups except high dose females which had a decreased survival. Highly significant increases (P<.001) in hepatocellular carcinoma were observed in both sexes of mice with incidences of: 98% and 95% for males and females at the high dose; 36% and 80% for males and females at the low dose as compared with 6% in both matched and colony control males, 0% in matched control females and 1% in colony control females. Nodular hyperplasia of the liver was observed in many low dose male mice that had not developed hepatocellular carcinoma.
  trichloromethane LEVELS OF EVIDENCE OF CARCINOGENICITY: Male Rats: Positive; Female Rats: Negative; Male Mice: Positive; Female Mice: Positive.