Metabolism of 1,1-dichloro-1-fluoroethane (HCFC-141b) in human volunteers
Tong, Z.; Utell, M.J.; Morrow, P.E.; Rusch, G.M.; Anders, M.W.
Drug Metabolism and Disposition the Biological Fate of Chemicals 26(7): 711-713
1998
ISSN/ISBN: 0090-9556 PMID: 9660855 Document Number: 492542
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. 'OF 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 beta-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.