Tissue acylation by the chlorofluorocarbon substitute 2,2-dichloro-1,1,1-trifluoroethane.
Hydrochlorofluorocarbons (HCFCs) are being developed as substitutes for ozone-depleting chlorofluorocarbons (CFCs); because widespread human exposure to HCFCs may be expected, it is important to evaluate their toxicities thoroughly. Here we report studies on the bioactivation of the CFC substitute 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) to an electrophilic intermediate that reacts covalently with liver proteins. HCFC-123 and its analog halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) were studied in rats by 19F NMR spectroscopy, and we found that a trifluoroacetylated lysine adduct was formed with liver proteins. Also, the pattern of proteins immunoreactive with hapten-specific anti-trifluoroacetylprotein antibodies was identical in livers of HCFC-123- and halothane-exposed rats. Because halothane causes an idiosyncratic, and sometimes fatal, hepatitis that is associated with an immune response against several trifluoroacetylated liver proteins, the present findings raise the possibility that humans exposed to HCFC-123 or structurally related HCFCs may be at risk of developing an immunologically mediated hepatitis.
Harris
J W
JW
Department of Pharmacology, University of Rochester, NY 14642.
Pohl
L R
LR
Martin
J L
JL
Anders
M W
MW
D000215:Acylation; D000818:Animals; D001711:Biotransformation; D017402:Chlorofluorocarbons; D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006846:Hydrocarbons, Halogenated / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008970:Molecular Weight; D011485:Protein Binding; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013347:Subcellular Fractions / Q000378:metabolism
D017402:Chlorofluorocarbons; D064227:Chlorofluorocarbons, Ethane; D005617:Chlorofluorocarbons, Methane; D006846:Hydrocarbons, Halogenated; D011506:Proteins; C067411:2,2-dichloro-1,1,1-trifluoroethane