METABOLISM AND PHARMACOKINETICS OF SELECTED HALON REPLACEMENT CANDIDATES

Metabolism studies were conducted using Fischer 344 and Sprague-Dawley rats following inhalation exposure to 1.0% (v/v) air atmospheres of 1 ,1-dichloro-2,2,2-trifluoroethane (HCFC-123),2-chloro-1,1,1,2-tetraflu oroethane (HCFC-124), 1-chloro-1,1-difluoroethane (HCFC-142b), bromoch lorodifluoromethane (Halon 1211), and perfluorohexane (PFH) for 2 h. T here were no remarkable differences in results between the two strains of rats. Animals exposed to HCFC-123 or HCFC-124 excreted trifluoroac etic acid in their urine. Urinary fluoride concentrations were increas ed in rats exposed to HCFC-124, and urinary bromide levels were increa sed in rats exposed to Halon 1211. Small quantities of volatile metabo lites 2-chloro-1,1,1-trifluoroethane (HCFC-133a) and 2-chloro-1,1-difl uoroethylene were observed in the livers of rats exposed to HCFC-123. Rats exposed to HCFC-142b excreted chlorodifluoroacetic acid in their urine; no volatile metabolites were detected in tissue samples. For PF H studies, no metabolites were detected in the urine or tissues of exp osed animals. These results are consistent with proposed oxidative and reductive pathways of metabolism for these chemicals. Pharmacokinetic studies were carried out in rats exposed by inhalation to 1.0%, 0.1%, or 0.01% of HCFC-123. Following exposure, blood concentrations of HCF C-123 fell sharply, whereas trifluoroacetic acid levels rose for appro x. 5 h and then declined gradually. Using a physiologically based phar macokinetic model, saturation of HCFC-123 metabolism was estimated to occur at approx. 0.2% (2000 ppm) HCFC-123.