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Rapid CommunicationShort Communication

Metabolism of 1,1-Dichloro-1-fluoroethane (HCFC-141b) in Human Volunteers

Zeen Tong, Mark J. Utell, Paul E. Morrow, George M. Rusch and M. W. Anders
Drug Metabolism and Disposition July 1998, 26 (7) 711-713;
Zeen Tong
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Mark J. Utell
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Paul E. Morrow
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George M. Rusch
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M. W. Anders
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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

  • Send reprint requests to: Dr. M. W. Anders, Department of Pharmacology and Physiology, University of Rochester, 601 Elmwood Ave., Box 711, Rochester, NY 14642.

  • 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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Drug Metabolism and Disposition
Vol. 26, Issue 7
1 Jul 1998
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Rapid CommunicationShort Communication

Metabolism of 1,1-Dichloro-1-fluoroethane (HCFC-141b) in Human Volunteers

Zeen Tong, Mark J. Utell, Paul E. Morrow, George M. Rusch and M. W. Anders
Drug Metabolism and Disposition July 1, 1998, 26 (7) 711-713;

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Rapid CommunicationShort Communication

Metabolism of 1,1-Dichloro-1-fluoroethane (HCFC-141b) in Human Volunteers

Zeen Tong, Mark J. Utell, Paul E. Morrow, George M. Rusch and M. W. Anders
Drug Metabolism and Disposition July 1, 1998, 26 (7) 711-713;
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