Defluorination of 1,1,1,2-tetrafluoroethane (R-134a) by rat hepatocytes

Add time:09/08/2019    Source:sciencedirect.com

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 head-space concentration of R-134a increased from 1% to 50% (balance of atmosphere 95% O25% 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-chloroethane), although not defluorinated by hepatocytes maintained with 95% O2, inhibited defluorination of R-134a. Hepatocytes from phenobarbitaltreated rats dehalogenated high (≥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.

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