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  • Title: Defluorination of the CFC-substitute 1,1,1,2-tetrafluoroethane: comparison in human, rat and rabbit hepatic microsomes.
    Author: Olson MJ, Surbrook SE.
    Journal: Toxicol Lett; 1991 Dec; 59(1-3):89-99. PubMed ID: 1755039.
    Abstract:
    1,1,1,2-Tetrafluoroethane (HFC-134a), which lacks ozone-depleting potential, has been selected as a replacement refrigerant for dichlorodifluoromethane (CFC-12) in air-conditioning and chiller applications, and as a propellant for pharmaceutical aerosols. A variety of paradigms using rats and rabbits have shown that HFC-134a has very little toxic potential. To strengthen the prediction of human hazard associated with HFC-134a exposure, we evaluated the rate of metabolism of this halocarbon by human hepatic microsomes relative to similar tissue preparations derived from rats and rabbits. Human microsomes defluorinated HFC-134a in a cytochrome-P-450-catalyzed reaction, common also to rat and rabbit. In absolute terms, the maximal rate of HFC-134a metabolism by human microsomes was very low, showed little interindividual variation among the samples evaluated (1.3 +/- 0.3 nmol F-/mg protein/15 min, mean +/- SD, n = 10), and did not exceed that in rat or rabbit liver microsomes. These findings support the argument that for characterization of HFC-134a toxicity, especially that which may be mediated by products of halocarbon metabolism, laboratory animals are an adequate surrogate for humans.
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