Vol. 26, Issue 7, 711-713, July 1998

SHORT 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

Department of Pharmacology and
Physiology (Z.T., M.W.A.)
Department of Medicine
(Pulmonary/Critical Care Unit)
(M.J.U.)
and Department of Environmental
Medicine (M.J.U., P.E.M., M.W.A.)
School of Medicine and Dentistry
University of Rochester,
and AlliedSignal Inc. (G.M.R.)

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 -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.