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© 1982 Oxford University Press

research-article

A Comparison of the Fate of Inhaled Methyl Chloroform (1,1,1-Trichloroethane) Following Single or Repeated Exposure in Rats and Mice

A.M. SCHUMANN, T.R. FOX and P.G. WATANABE

Toxicology Research Laboratory, Health and Environmental Sciences USA, Dow Chemical USA, 1803 Building, Midland, MI 48640

A Comparison of the Fate of Inhaled Methyl Chloroform (1,1,1-Trichloroethane) Following Single or Repeated Exposure in Rats and Mice. Schumann, A.M., Fox, T.R. and Watanabe, P.G. (1982). Fundam. Appl. Toxicol. 2:27–32. Male Fischer 344 rats and B6C3F1 mice were exposed by inhalation to 1500 ppm of methyl chloroform (MC) 6 hours/day, 5 days/week for approximately 16 months. On the last day of repeated exposure 14C-labeled MC was used. The fate of the 14C-MC in the repeatedly exposed animals was compared to a group of rats and mice which had been exposed concurrently for 16 months to chamber air (age-matched controls) prior to receiving the single 6 hour exposure to 1500 ppm of 14C-MC. The routes of excretion and tissue concentration of 14C activity were similar between the singly and repeatedly exposed rats and mice. The major route of elimination of MC was exhalation of the parent chemical In the expired air and constituted approximately 97% of the total recovered radioactivity in rats and 92–94% in mice. The remaining radioactivity (~3.9%) was recovered as metabolized MC in the expired air (14CO2) and as nonvolatile radioactivity in the urine, feces, carcass and cage wash. Mice were found to eliminate MC more rapidly via the pulmonary route and to biotransform approximately 5-fold more MC on a body weight basis than rats. Repeated exposure to MC did not significantly affect the disposition of MC compared to the singly exposed rats and mice. Thus even after long-term repeated exposure to MC, its biotransformation remains limited. Comparison of the results of the present study to those obtained previously in young-adult rats and mice indicates that alterations in the pharmacokinetics of 14C-MC (increased body burden and decreased rate of pulmonary elimination) occur with age but not prior repeated exposure to MC.


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