Abstract
Human subjects were exposed by inhalation to 250, 500, and 1000 ppm 1,1-dichloro-1-fluoroethane (HCFC-141b) for 4 hr, and urine samples were collected from 0–4, 4–12, and 12–24 hr for metabolite analysis.19F nuclear magnetic resonance spectroscopic analysis of urine samples from exposed subjects showed that 2,2-dichloro-2-fluoroethyl glucuronide and dichlorofluoroacetic acid were the major and minor metabolites, respectively, of HCFC-141b. Urinary 2,2-dichloro-2-fluoroethyl glucuronide was hydrolyzed to 2,2-dichloro-2-fluoroethanol by incubation with β-glucuronidase, and the released 2,2-dichloro-2-fluoroethanol was quantified by gas chromatography/mass spectrometry. Concentrations of 2,2-dichloro-2-fluoroethanol were highest in the urine samples collected 4–12 hr after exposure, but 2,2-dichloro-2-fluoroethanol was also detected in the samples collected 0–4 and 12–24 hr after exposure. Exposure concentration–dependent excretion of 2,2-dichloro-2-fluoroethanol, obtained by hydrolysis of 2,2-dichloro-2-fluoroethyl glucuronide, was observed in seven of the eight subjects studied. In conclusion, HCFC-141b is metabolized in human subjects to 2,2-dichloro-2-fluoroethanol, which is conjugated with glucuronic acid and excreted as its glucuronide in urine in a time- and exposure concentration–dependent manner.
Footnotes
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Send reprint requests to: Dr. M. W. Anders, Department of Pharmacology and Physiology, University of Rochester, 601 Elmwood Ave., Box 711, Rochester, NY 14642.
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This research was supported by AlliedSignal Inc. A preliminary report of this work was presented at the 8th North American International Society for the Study of Xenobiotics meeting, Hilton Head, SC, October 26–30, 1997.
- Abbreviations used are::
- CFCs
- chlorofluorocarbons
- HCFCs
- hydrochlorofluorocarbons
- HCFC-141b
- 1,1-dichloro-1-fluoroethane
- NMR
- nuclear magnetic resonance
- Received December 31, 1997.
- Accepted March 23, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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