Defluorination of 1,1,1,2-tetrafluoroethane (R-134a) by rat hepatocytes.
As part of its toxicological evaluation we assessed the in vitro metabolism of 1,1,1,2-tetrafluoroethane (R-134a), a non-ozone-depleting chemical likely to replace dichlorodifluoromethane (R-12) as an air-conditioning refrigerant. Hepatocyte suspensions in sealed flasks produced increasing quantities of F- (detected in the liquid media) as the headspace concentration of R-134a increased from 1% to 50% (balance of atmosphere 95% O2-5% CO2); the kinetics of defluorination suggested substrate-saturation. Little F- was detected in cultures without R-134a or in cell suspensions heated prior to addition of R-134a. Halothane (1,1,1-trichloro-2-bromo-2-chloro-ethane), although not defluorinated by hepatocytes maintained with 95% O2, inhibited defluorination of R-134a. Hepatocytes from phenobarbital-treated rats dehalogenated high (greater than or equal to 25%) concentrations of R-134a at greater rates than cells from untreated rats. These findings are consistent with the hypothesis that oxidative metabolism of R-134a by cytochrome P-450 can occur in vivo.
Olson
M J
MJ
Biomedical Science Department, General Motors Research Laboratories, Warren, MI 48090.
Reidy
C A
CA
Johnson
J T
JT
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D006221:Halothane / Q000378:metabolism / Q000494:pharmacology; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D011199:Potentiometry; D051381:Rats; D011916:Rats, Inbred F344; D004980:Ethane / Q000031:analogs & derivatives; D005466:Fluorocarbons
D006221:Halothane; D006845:Hydrocarbons, Fluorinated; D010634:Phenobarbital; C063006:norflurane; D004980:Ethane; D005466:Fluorocarbons