Identification and quantification of fluorine-containing metabolites of 1-chloro-2,2,2-trifluoroethane (HCFC133A) in the rat by 19F-NMR spectroscopy.
1-Chloro-2,2,2-trifluorethane (HCFC133a) causes a reduction in testis weight and germinal epithelial cell atrophy in the rat following exposure by inhalation at concentrations of 10,000 ppm and above. Following administration by gavage, an increased incidence of Leydig cell tumors of the testis was seen. The metabolism of HCFC133a has been investigated in respect to the known toxicity of this compound. Male rats were exposed by inhalation to an atmosphere of 50,000 ppm HCFC133a for a period of 6 hr. Analysis of urine, collected during the exposure period and up to 48 hr following exposure, by 19F-NMR spectroscopy identified 2,2,2-trifluoroethanol (TFE; and its beta-glucuronide), trifluoroacetaldehyde (TFAA; as its hydrate and urea adduct), and trifluoroacetic acid (TFA) as fluorine-containing metabolites of HCFC133a. Of the total amount of metabolite eliminated in urine, 83% was excreted within 24 hr postdose, establishing a rapid elimination of metabolites by this route. TFAA, an established testicular toxicant, was the major metabolite accounting for 57% of the total fluorinated metabolites eliminated in urine, whereas TFA and TFE accounted for 29% and 14%, respectively. The presence of these metabolites in urine is consistent with an oxidative route of metabolism of this fluorocarbon.
Ellis
M K
MK
Investigative Toxicology Section, Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Naylor
J L
JL
Green
T
T
Collins
M A
MA
D000818:Animals; D001711:Biotransformation; D005966:Glucuronidase / Q000378:metabolism; D006221:Halothane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
C016800:1,1,1-trifluoro-2-chloroethane; D005966:Glucuronidase; D006221:Halothane