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. 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 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.
Tong
Z
Z
Department of Pharmacology and Physiology, University of Rochester, Rochester, NY 14642, USA.
Utell
M J
MJ
Morrow
P E
PE
Rusch
G M
GM
Anders
M W
MW
D000328:Adult; D017402:Chlorofluorocarbons / Q000378:metabolism*; D064227:Chlorofluorocarbons, Ethane; D004305:Dose-Response Relationship, Drug; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male
D017402:Chlorofluorocarbons; D064227:Chlorofluorocarbons, Ethane; D005965:Glucuronates; C068320:1,1-dichloro-1-fluoroethane