Gas-uptake pharmacokinetics and metabolism of 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124) in the rat, mouse, and hamster
Loizou, G.D.; Anders, M.W.
Drug Metabolism and Disposition the Biological Fate of Chemicals 23(8): 875-880
1995
ISSN/ISBN: 0090-9556 PMID: 7493556 Document Number: 444755
Gas-uptake pharmacokinetics and metabolism of the chlorofluorocarbon replacement 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124) were investigated in rats, mice, and hamsters. Species differences in the rate of uptake of HCFC-124 and urinary excretion of trifluoroacetic acid were observed. In rats and mice, the uptake of HCFC-124 was described by both saturable and first-order components, whereas in the hamster only first-order uptake was observed. The in vivo metabolic rate constants obtained from computer simulation of the gas-uptake data were: for rats-K-M = 1.2 mg liter-1 (8.79 mmol liter-1, V-maxc = 0.35 +- 0.01 mg kg-1 hr-1 (2.56 +- 0.01 mmol kg-1 hr-1), and k-fc = 1.25 +- 0.01 hr-1 kg-231; for mice-K-M = 1.2 mg liter-1 (8.79 mmol liter-1), V-maxc = 1.78 +- 0.01 mg kg-1 hr-1 (13.0 +- 0.007 mmol kg-1 hr-1), and k-fc = 4.08 +- 0.01 hr-1 kg-1; and for hamsters-k-fc = 1.47 +- 0.02 hr-1 kg-1. The production and excretion of trifluoroacetic acid, the major urinary metabolite of HCFC-124, were also simulated in rats and mice, but not in hamsters, by the physiologically based pharmacokinetic model when the in vivo metabolic rate constants obtained in the gas-uptake simulation studies were used. The blood:air partition coefficient of HCFC-124 in the hamster was lower than in the rat or mouse. A low blood:air partition coefficient may limit the pulmonary uptake of volatile chemicals. Therefore, species that show blood:air partition coefficients much lower than those found in humans may not be suitable for use in chemical hazard evaluation and human risk assessment.