A. M. Schumann, Tony R. Fox, P. Watanabe
Mar 15, 1982
Citations
1
Influential Citations
51
Citations
Quality indicators
Journal
Toxicology and applied pharmacology
Abstract
Studies on the pharmacokinetics of [14C]methyl chloroform (1,1,1-trichloroethane) in male Fischer 344 rats and B6C3F1 mice were undertaken to characterize the disposition of the inhaled chemical over a wide range of exposure concentrations. The animals were exposed to 150 or 1500 ppm of [14C]methyl chloroform vapor for 6 hr and the elimination of 14C activity was followed for 72 hr. Following exposure to either concentration of methyl chloroform, both species excreted >96% of the total recovered radioactivity during the first 24 hr. The major route of elimination of methyl chloroform was via exhalation of unchanged chemical in the expired air which constituted approximately 94–98% of the total recovered radioactivity in rats and 87–97% in mice at 150 and 1500 ppm, respectively. Mice were found to eliminate methyl chloroform in the expired air more rapidly than did rats. The remaining radioactivity (approximately, 2–13%) was detected as metabolized methyl chloroform in the expired air (14CO2) and as nonvolatile radioactivity in the urine, feces, carcass, and cage wash. Although mice were found to metabolize two to three times more methyl chloroform on a body weight basis, the biotransformation of methyl chloroform was shown to be a saturable, dose-dependent process in both species. Since the biotransformation of methyl chloroform occurred to such a limited extent, saturation of its metabolism did not impact markedly on the distribution or elimination of the parent chemical. The body burden, end-exposure blood level, and tissue concentration of methyl chloroform were found overall to increase in direct proportion with the exposure concentration. [14C]Methyl chloroform was more concentrated in the fat of both species than in the liver or kidneys immediately after exposure. However it was rapidly cleared from the fat so that by 24 hr <2% of the initial radioactivity remained. Thus, methyl chloroform shows little potential for significant bioaccumulation in rodents.