METABOLISM OF 1,1-DICHLORO-1-FLUOROETHANE (HCFC-141B) IN HUMAN VOLUNTEERS

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. F-19 nuclear magnetic resonance spectroscopic analysis of urine samples fro m exposed subjects showed that 2,2-dichloro-2-fluoroethyl glucuronide and dichlorofluoroacetic acid were the major and minor metabolites, re spectively, of HCFC-141b, Urinary 2,2-dichloro-2-fluoroethyl glucuroni de was hydrolyzed to 2,2-dichloro-2-fluoroethanol by incubation with b eta-glucuronidase, and the released 2,2-dichloro-2-fluoroethanol was q uantified by gas chromatography/mass spectrometry. Concentrations of 2 ,2-dichloro-2-fluoroethanol were highest in the urine samples collecte d 4-12 hr after exposure, but 2,2-dichloro-2-fluoroethanol was also de tected in the samples collected 0-4 and 12-24 hr after exposure. Expos ure 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 glucuron ide in urine in a time- and exposure concentration-dependent manner.