Defluorination of the CFC-substitute 1,1,1,2-tetrafluoroethane: comparison in human, rat and rabbit hepatic microsomes.
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.
Olson
M J
MJ
Biomedical Science Department, General Motors Research Laboratories, Warren, MI 48090-9055.
Surbrook
S E
SE
D000777:Anesthetics / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001711:Biotransformation; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009596:Nitrophenols / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D004980:Ethane / Q000031:analogs & derivatives; D005466:Fluorocarbons
D000777:Anesthetics; D006845:Hydrocarbons, Fluorinated; D009596:Nitrophenols; C063006:norflurane; D004980:Ethane; D005466:Fluorocarbons; C024836:4-nitrophenol