IDENTIFICATION AND QUANTIFICATION OF FLUORINE-CONTAINING METABOLITES OF 1-CHLORO-2,2,2-TRIFLUOROETHANE (HCFC133A) IN THE RAT BY F-19-NMR SPECTROSCOPY

Citation
Mk. Ellis et al., IDENTIFICATION AND QUANTIFICATION OF FLUORINE-CONTAINING METABOLITES OF 1-CHLORO-2,2,2-TRIFLUOROETHANE (HCFC133A) IN THE RAT BY F-19-NMR SPECTROSCOPY, Drug metabolism and disposition, 23(1), 1995, pp. 102-106
Citations number
22
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00909556
Volume
23
Issue
1
Year of publication
1995
Pages
102 - 106
Database
ISI
SICI code
0090-9556(1995)23:1<102:IAQOFM>2.0.ZU;2-7
Abstract
1-Chloro-2,2,2-trifluoroethane (HCFC133a) causes a reduction in testis weight and germinal epithelial cell atrophy in the rat following expo sure by inhalation at concentrations of 10,000 ppm and above. Followin g administration by gavage, an increased incidence of Leydig cell tumo rs of the testis was seen. The metabolism of HCFC133a has been investi gated in respect to the known toxicity of this compound. Male rats wer e exposed by inhalation to an atmosphere of 50,000 ppm HCFC133a for a period of 6 hr. Analysis of urine, collected during the exposure perio d and up to 48 hr following exposure, by F-19-NMR spectroscopy identif ied 2,2,2-trifluoroethanol (TFE; and its beta-glucuronide), trifluoroa cetaldehyde (TFAA; as its hydrate and urea adduct), and trifluoroaceti c acid (TFA) as fluorine-containing metabolites of HCFC133a. Of the to tal amount of metabolite eliminated in urine, 83% was excreted within 24 hr postdose, establishing a rapid elimination of metabolites by thi s route. TFAA, an established testicular toxicant, was the major metab olite accounting for 57% of the total fluorinated metabolites eliminat ed in urine, whereas TFA and TFE accounted for 29% and 14%, respective ly. The presence of these metabolites in urine is consistent with an o xidative route of metabolism of this fluorocarbon.