Toxicity of trihalomethanes: I. The acute and subacute toxicity of chloroform, bromodichloromethane, chlorodibromomethane and bromoform in rats.

In an acute study, groups of 10 male and 10 female rats were given single oral doses of chloroform, bromodichloromethane (BDCM), chlorodibromomethane (CDBM), or bromoform and were observed for clinical symptoms for the following 14 days. Median lethal doses (LD 50) of the four trihalomethanes were found to be between 848 and 1388 mg/kg. Some groups which survived the treatment for 14 days showed reduced food intake, growth retardation and increased liver and kidney weight. Elevated serum cholesterol levels were observed in the surviving male rats treated with chloroform and CDBM, and in the females treated with chloroform. Decreased liver protein content occurred in male but not female rats fed chloroform and bromoform. In contrast, increase aniline hydroxylase activity was observed in female rats fed chloroform but not bromoform. Hematological values which were altered by the four trihalomethanes were hemoglobin, hematocrit, RBC, WBC, neutrophil and lymphocyte counts. Treatment-related histologic changes were observed in the liver and kidney of rats. These changes were qualitatively and quantitatively similar for the four trihalomethanes. These data indicate that trihalomethanes at large single oral doses can produce a wide range of toxic changes in the rat. In a subacute study, groups of 10 male rats were fed four trihalomethanes at 0, 5, 50 or 500 ppm in their drinking water for 28 days. The growth rate and food intake were not affected by treatment. A slight increase in relative kidney weight was observed in the groups fed 5 ppm chloroform; 500 ppm bromoform, 5 and 500 ppm BDCM. The animals fed the highest dose of chloroform showed decreased neutrophils. Serum biochemical parameters and hepatic microsomal enzyme activities were not altered by any of the four trihalomethanes. No histopathological changes were seen in the tissues examined.