Metabolism in vivo and in vitro of the refrigerant substitute 1,1,1,2-tetrafluoro-2-chloroethane

Journal Article · Sun Sep 01 00:00:00 EDT 1991 · Drug Metabolism and Disposition; (United States)

OSTI ID:5679217

Olson, M J; Johnson, J T; O'Gara, J F; Surbrook, Jr, S E ^[1]

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1. Biomedical Science Department, General Motors Research Laboratories, Warren, MI (United States)

Ternary mixtures of hydrochlorofluorocarbons and hydrofluorocarbons are being evaluated as refrigerant substitutes for dichlorodifluoromethane, which is to be banned from further production in 2000. A priori consideration of the similarity between 1,1,1,2-tetrafluoro-2-chloroethane (HCFC-124), a primary component of candidate refrigerant blends, and halothane suggests that metabolism of HCFC-124 might proceed via reactive intermediates. Our data show that rats exposed for 2 hr to approximately 10,000 ppm HCFC-124 excreted both inorganic fluoride (F-) and trifluoroacetic acid (TFA), identified by 9F-NMR, in the urine. Likewise, microsomes produced F- and TFA from HCFC-124 in an NADPH-dependent, CO-inhibited, aerobic reaction. Treatment of rats with pyridine caused about a 20-fold increase in aerobic microsomal metabolism (F- release) of HCFC-124, while the rate of defluorination was slightly decreased by phenobarbital administration. An antibody to cytochrome P450 IIE1 inhibited more than 90% of HCFC-124 metabolism in pyridine-induced preparations. Defluorination of HCFC-124 by microsomes also occurred under conditions of greatly reduced oxygen tension, demonstrating that this halocarbon can be reductively metabolized. Moreover, heat-inactivated, NADPH-reduced microsomes liberated F- and a fluorinated organic product, although not TFA, from HCFC-124. Formation of TFA and F- as products of oxidative HCFC-124 metabolism support the hypothesis that trifluoroacetyl fluoride is formed as an intermediate. Trifluoroacetyl halides are known to adduct tissue proteins. The reductive metabolism of HCFC-124, by analogy to halothane, may produce a radical (CHFCF3) capable of biological interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

• OSTI ID: 5679217
• Journal Information: Drug Metabolism and Disposition; (United States), Journal Name: Drug Metabolism and Disposition; (United States) Vol. 19:5; ISSN DMDSA; ISSN 0090-9556
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BODY
CELL CONSTITUENTS
COENZYMES
DIGESTIVE SYSTEM
DISPERSIONS
FREONS
GLANDS
HALOGENATED ALIPHATIC HYDROCARBONS
IN VITRO
IN VIVO
LIVER
MAGNETIC RESONANCE
MAMMALS
METABOLISM
MICROSOMES
MIXTURES
NADP
NUCLEAR MAGNETIC RESONANCE
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
RATS
RESONANCE
RIBOSOMES
RODENTS
VERTEBRATES