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
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.