Subchronic Inhalation Toxicity of 1,1,1,3-Tetrachloropropane in Rats

The purpose of this study was to evaluate the inhalation toxicityof 1,1,1,3-tetrachloropropane (TCP), an intermediate in productionof chlorinated silicone fluids. Male and female Sprague- Dawleyrats were exposed 6 hr/day, 5 days/week, for days to TCP atconcentrations of 0, 25, 75, or 225 ppm (Phase study) and to0, 1, 5, or 10 ppm (Phase II study). Phase II of study was conductedbecause a no-observed-effect level was not achieved in PhaseI. No animals died during the study. Clinical signs of toxicityincluded oral, nasal, and/or ocular discharge. No statisticallysignificant differences were observed in either body weightsor food consumption between exposed and control animals. Clinicalpathology did not indicate any treatment related effects. Absoluteand relative liver and kidney weights were increased in maleand female rats exposed to 225 ppm TCP, and heart weights wereincreased in male rats exposed to 225 ppm TCP. The liver andheart weight changes were supported by the findings of microscopiclesions in these organs. These lesions consisted of multifocal/focalmyofiber degeneration necrosis with adjacent chronic myocarditisin the heart and multifocal single-cell necrosis in the liverparenchyma. The liver lesions had essentially resolved at theend of a 28-day recovery period but the heart lesions were stillpresent in male rats in the recovery group exposed to 225 ppmTCP. No treatment-related effects were observed in animals exposedto 1, 5, or 10 ppm TCP. The data of this study showed that theno-observable-effect level for TCP was 10 ppm in male and femaleCD rats.