Carcinogenicity and Chronic Toxicity in Rats and Mice Exposed to Chloroform by Inhalation

Abstract

A bioassay study of carcinogenicity and chronic toxicity of chloroform was undertaken by inhalation exposures of groups of 50 F344 rats and 50 BDF₁ mice of both sexes to chloroform for 6 h/d × 5 d/wk × 104 wk. The exposure concentration was 0 (control), 10, 30 or 90 ppm for rats and 0, 5, 30 or 90 ppm for mice. Combined incidences of renal cell adenomas and carcinomas, and of hepatocellular adenomas and carcinomas increased in the exposed male and female mice, respectively. Incidences of atypical tubule hyperplasia, cytoplasmic basophilia and nuclear enlargement in the kidneys and fatty change in the liver increased in the exposed male mice. Increased incidence of altered cell foci in the exposed female mice was causally related to the hepatocellular adenomas and carcinomas. No significantly increased incidence of the kidney or liver tumors was observed in the exposed rats of either sex. Increased incidences of nuclear enlargement and dilatation of tubular lumen were found in the kidneys of exposed rats. No-observed-adverse-effect-levels (NOAELs) for the biologically significant endpoint were determined from the dose-response relationships of the present datasets. The NOAEL for the histopathological endpoint of the kidneys resulted in 5 ppm for mice and 10 ppm for rats. An occupational exposure limit for chloroform was discussed in light of the NOAELs.