SUBCHRONIC INHALATION TOXICITY OF 1,1,1,3-TETRACHLOROPROPANE IN RATS

The purpose of this study was to evaluate the inhalation toxicity of 1 ,1,1,3-tetrachloropropane (TCP), an intermediate in the production of chlorinated silicone fluids, Male and female Sprague-Dawley rats were exposed 6 hr/day, 5 days/week, for 90 days to TCP at concentrations of 0, 25, 75, or 225 ppm (Phase I study) and to 0, 1, 5, or 10 ppm (Phas e II study). Phase II of the study was conducted because a no-observed -effect level was not achieved in Phase I. No animals died during the study. Clinical signs of toxicity included oral, nasal, and/or ocular discharge, No statistically significant differences were observed in e ither body weights or food consumption between exposed and control ani mals, Clinical pathology did not indicate any treatment-related effect s. Absolute and relative liver and kidney weights were increased in ma le and female rats exposed to 225 ppm TCP, and heart weights were incr eased in male rats exposed to 225 ppm TCP. The liver and heart weight changes were supported by the findings of microscopic lesions in these organs. These lesions consisted of multifocal/focal myofiber degenera tion necrosis with adjacent chronic myocarditis in the heart and multi focal single-cell necrosis in the liver parenchyma. The liver lesions had essentially resolved at the end of a 28-day recovery period but th e heart lesions were still present in male rats in the recovery group exposed to 225 ppm TCP, No treatment-related effects were observed in animals exposed to 1, 5, or 10 ppm TCP. The data of this study showed that the no-observable-effect level for TCP was 10 ppm in male and fem ale CD rats. (C) 1995 Society of Toxicology.