Metabolism of the hydrochlorofluorocarbon 1,2-dichloro-1,1-difluoroethane.
1,2-Dichloro-1,1-difluoroethane (HCFC-132b) is a potential substitute for some ozone-depleting chlorofluorocarbons and a model for other 1,1,1,2-tetrahaloethanes under consideration as chlorofluorocarbon substitutes. Male Fischer 344 rats were given 10 mmol/kg HCFC-132b dissolved in corn oil by intraperitoneal injection. An NMR assay for covalent binding of HCFC-132b metabolites to liver proteins was negative, whereas binding was observed in halothane-treated rats. Total urinary metabolites excreted by rats given HCFC-132b during the first 24 h amounted to 1.8 +/- 0.1% of the injected dose, as determined by 19F NMR. During the first 6 h, metabolites of HCFC-132b corresponding to 2-chloro-2,2-difluoroethyl glucuronide, unknown metabolite A, chlorodifluoroacetic acid, and chlorodifluoroacetaldehyde hydrate [both free and conjugated (unknown metabolite B)] were excreted in urine in the approximate ratio 100:9:3:7, respectively. Metabolite A is apparently an O-conjugate of 2-chloro-2,2-difluoroethanol; unconjugated 2-chloro-2,2-difluoroethanol was not detected in urine. The 19F NMR spectrum of metabolite B indicates the formation of a hemiacetal of chlorodifluoroacetaldehyde. Repeated exposure of rats to HCFC-132b significantly increased both the rate of chlorodifluoroacetic acid excretion and the relative fraction of the HCFC-132b dose excreted as chlorodifluoroacetic acid in urine. Incubation of HCFC-132b with rat hepatic microsomes yielded chlorodifluoroacetaldehyde hydrate as the only fluorinated product. The in vitro metabolism of HCFC-132b was increased in microsomes from pyridine-treated rats as compared with control rats, and HCFC-132b metabolism was inhibited by p-nitrophenol, indicating that the cytochrome P-450 isoform IIE1 is largely responsible for the initial hydroxylation of HCFC-132b.
Harris
J W
JW
Environmental Health Sciences Center, University of Rochester School of Medicine, New York 14642.
Anders
M W
MW
D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000652:urine; D000085:Acetates / Q000652:urine; D000818:Animals; D017402:Chlorofluorocarbons; D064227:Chlorofluorocarbons, Ethane; D005461:Fluorine; D006846:Hydrocarbons, Halogenated / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344
D000085:Acetates; D017402:Chlorofluorocarbons; D064227:Chlorofluorocarbons, Ethane; D006846:Hydrocarbons, Halogenated; C072793:1,2-dichloro-1,1-difluoroethane; D005461:Fluorine; C072794:chlorodifluoroacetic acid; C072795:chlorodifluoroacetaldehyde; D000079:Acetaldehyde