METABOLISM OF 1-FLUORO-1,1,2-TRICHLOROETHANE, 1,2-DICHLORO-1,1-DIFLUOROETHANE, AND 1,1,1-TRIFLUORO-2-CHLOROETHANE

1-Fluoro-1,1,2-trichloroethane (HCFC-131a), 1,2-dichloro-1,1-difluoroe thane (HCFC-132b), and 1,1,1-trifluoro-2-chloroethane (HCFC-133a) were chosen as models for comparative metabolism studies on 1,1,1,2-tetrah aloethanes, which are under consideration as replacements for ozone-de pleting chlorofluorocarbons (CFCs)., Male Fischer 344 rats were given 10 mmol/kg ip HCFC-131a or HCFC-132b or exposed by inhalation to 1% HC FC-133a for 2 h. Urine collected in the first 24 h after exposure was analyzed by F-19 NMR and GC/MS and with a fluoride-selective ion elect rode for the formation of fluorine-containing metabolites. Metabolites of HCFC-131a included 2,2-dichloro-2-fluoroethyl glucuronide, 2,2-dic hloro-2-fluoroethyl sulfate, dichlorofluoroacetic acid, and inorganic fluoride. Metabolites of HCFC-132b were characterized as 2-chloro-2,2- difluoroethyl glucuronide, 2-chloro-2,2-difluoroethyl sulfate, chlorod ifluoroacetic acid, chlorodifluoroacetaldehyde hydrate, chlorodifluoro acetaldehyde-urea adduct, and inorganic fluoride. HCFC-133a was metabo lized to 2,2,2-trifluoroethyl glucuronide, trifluoroacetic acid, trifl uoroacetaldehyde hydrate, trifluoroacetaldehyde-urea adduct, inorganic fluoride, and a minor, unidentified metabolite. With HCFC-131a and HC FC-132b, glucuronide conjugates of 2,2,2-trihaloethanols were the majo r urinary metabolites, whereas with HCFC-133a, a trifluoroacetaldehyde -urea adduct was the major urinary metabolite. Analysis of metabolite distribution in vivo indicated that aldehydic metabolites increased as fluorine substitution increased in the order HCFC-131a < HCFC-132b < HCFC-133a. With NADPH-fortified rat liver microsomes, HCFC-133a and HC FC-132b were biotransformed to trifluoroacetaldehyde and chlorodifluor oacetaldehyde, respectively, whereas HCFC-131a was converted to dichlo rofluoroacetic acid. No covalently bound metabolites of HCFC-131a and HCFC-133a metabolites were detected by F-19 NMR spectroscopy. The natu re of the identified organic fluorine-containing metabolites indicates that cytochrome P-450-dependent oxidation predominates in the metabol ism of these 1,1,1,2-tetrahaloethanes. The generation of fluoride from the fluorodihalomethyl group (-CFX(2)) apparently arises from a separ ate dehalogenation pathway.