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Abstract for TR-3

Bioassay of 1,1,1-Trichloroethane for Possible Carcinogenicity

CASRN: 71-55-6
Chemical Formula: C2H3Cl3
Molecular Weight: 133.41
Synonyms/Common Names: Methylchloroform
Report Date: January 1977

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Abstract

1,1,1-Trichloroethane is one of a group of halogenated hydrocarbons selected for testing in the Carcinogenesis Bioassay Program. The rationale for its selection included its structural relationship to carbon tetrachloride, its wide use in industry, its extensive exposure of humans, and the incomplete knowledge of its carcinogenic potential. In 1959, Browning reported that 1,1,2-trichloroethane was replacing the more toxic industrial solvents: trichloroethylene, tetrachloroethylene, and carbon tetrachloride. The Environmental Protection Agency permits 1,1,1-trichloroethane to be used as a solvent or cosolvent in pesticide formulations for the postharvest fumigation of citrus fruits.

The carcinogenesis bioassay of technical grade 1,1,1-trichloroethane was conducted using Osborne-Mendel rats and B6C3F1 mice. 1,1,1-Trichloroethane was administered orally by gavage in corn oil to 50 animals of each sex and species at two dose levels 5 days per week for 78 weeks.

Rats: The experiment was originally started using doses of 3,000 and 1,500 mg/kg of body weight. After a few weeks the study was terminated, and the animals discarded because of marked signs of intoxication. The experiment was restarted with rats 7 weeks of age that were put on doses of 1,500 and 750 mg/kg. There was a moderate depression of body weight in the first year of the study. During the second year a yellow discoloration of the fur of the lower abdomen and increased eye and nasal discharge and dyspnea were noted. Both males and females given the test chemical exhibited early mortality when compared with the untreated controls, and the statistical test for dose-related trend was significant (P<0.04). All surviving animals were killed at 117 weeks of age.

Mice: Male and female weanlings were started on test at 5 weeks of age and killed at 96 weeks of age. Initially, the doses for male and female mice were 4,000 and 2,000 mg/kg body weight. During the 10th week of the study, doses were increased to 5,000 and 2,500 mg/kg, since the animals apparently could tolerate a higher dose. Doses were again increased at week 20 to 6,000 and 3,000 mg/kg and maintained at these levels to the end of the study. Time-weighted average doses for the high- and low-dose mice were, respectively, 5,615 and 2,807 mg/kg. There was a moderate depression of body weight throughout the study in both sexes of mice, and the survival was significantly decreased. In the female mice, there was a positive dose-related trend (P=0.002) in the proportions surviving.

A variety of neoplasms were represented in both 1,1,1-trichloroethane-treated and matched-control rats and mice. However, each type of neoplasm has been encountered previously as a lesion in untreated rats or mice. The neoplasms observed are not believed attributable to 1,1,1-trichloroethane exposure, since no relationship was established between the dosage groups, the species, sex, type of neoplasm, or the site of occurrence. Even if such a relationship were inferred, it would be inappropriate to make an assessment of carcinogenicity of 1,1,1-trichloroethane on the basis of this test, because of the abbreviated life spans of both the rats and the mice.