RT Journal Article
SR Electronic
T1 Metabolism of 1,1-Dichloro-1-fluoroethane (HCFC-141b) in Human Volunteers
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 711
OP 713
VO 26
IS 7
A1 Zeen Tong
A1 Mark J. Utell
A1 Paul E. Morrow
A1 George M. Rusch
A1 M. W. Anders
YR 1998
UL http://dmd.aspetjournals.org/content/26/7/711.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics