Fate of [ 14C]vinyl chloride after single oral administration in rats

Abstract

Male rats were given single oral doses of 0.05, 1, and 100 mg/kg of [ 14C]vinyl chloride (VC), and the routes and rates of elimination of 14C activity followed for 72 hr. Following 0.05 and 1 mg/kg, excretion in the urine as nonvolatile metabolites and as 14CO 2 in expired air accounted for 59–68% and 9–13%, respectively of the administered dose. Only 1–2% of the dose was expired by the lungs as VC. Conversely, after 100 mg/kg, 67% of the dose was eliminated by the lungs as VC, while urinary nonvolatile metabolites and 14CO 2 comprised 11 and 3%, respectively. Pulmonary elimination after 100 mg/kg showed an apparent biphasic clearance with haif-times ( t 1 2 ) of 14.4 and 40.8 min for the respective fast and slow phases. Following 0.05 and 1 mg/kg the pulmonary clearance of VC was monophasic with t 1 2 of 53.3 and 57.8 min. The percentage of the dose remaining in the carcass after 72 hr was 10, 11, and 2% for the 0.05-, 1- and 100-mg/kg doses, respectively. The urinary radio-activity was separated by high pressure liquid chromatography into three major metabolites. Two of the three major urinary metabolites have been identified as N-acetyl- S-(2-hydroxyethyl)-cysteine and thiodiglycolic acid by gas chromatography-mass spectrometry. The proportions of the urinary metabolites were not influenced by the dose. The fate of VC following an oral dose between 1 and 100 mg/kg was clearly dose-dependent. Consistent with our previous studies on the fate of VC following inhalation exposure in rats, the metabolism of VC appears to be a saturable process.