Results of a 90-day toxicity study on 1,2,3- and 1,1,2-trichloropropane administered via the drinking water

Abstract

Trichloropropanes have been identified as environmental contaminants in sediments of the Great Lakes region of North America. Since these chemicals had the potential to find their way into drinking water, a 90-day feeding study was carried out in order to determine their subchronic toxicity. Groups of 10 male and 10 female weanling Sprague-Dawley rats were supplied drinking water ad libitum, containing 1,2,3- or 1,1,2-trichloropropane at concentrations of 1, 10, 100 or 1000 mg/L for 13 weeks. Emulphor (0.5%) was used to solubilize the chemicals. At the end of the study, the animals were killed and examined for gross and microscopic changes. Heart, liver, brain, kidney and spleen were excised and weighed. Blood was collected and subjected to a comprehensive hematological analysis. Serum was collected and profiled for changes in 12 biochemical parameters and a portion of liver was used to determine mixed function oxidase activity. Although three animals died during the study, their deaths could not be related to treatment. Decreased growth rate was observed in both sexes of the group receiving 1000 mg/L 1,2,3-trichloropropane. There was an increase in liver, kidney and brain weights (relative to body weight) in rats of both sexes fed 1000 mg/L 1,2,3-trichloropropane. Fatty livers were observed in some of the treated animals but a clear dose-relationship was not evident. An elevation in serum cholesterol was observed in female rats fed the highest dose of 1,2,3-trichloropropane. This chemical also induced hepatic aminopyrine demethylase and aniline hydroxylase activities in male rats at the highest dose. Administration of both isomers produced only mild histological changes in the liver, thyroid and kidney of rats at the highest dose. The changes in the liver consisted of an increase in cytoplasmic eosinophilia in the periportal area together with vesiculation of biliary epithelial nuclei. Morphological changes were characterized by increased anisokaryosis in the proximal epithelium and occasional pyknosis associated with the accumulation of large eosinophilic inclusions. Changes in the thyroid consisted of a mild reduction in follicular size associated with an increased epithelial height. In general, these changes were more severe in the males than females, but were still mild overall. It was concluded that the no-effect level for both chemicals was 100 mg/L (15–20 mg/kg bw/day) and based on effects on growth rate and other changes, the 1,2,3- isomer was judged to be slightly more toxic than the 1,1,2- isomer.