The pharmacokinetics of [ 14C]vinylidene chloride in rats following inhalation exposure

Abstract

Studies on the pharmacokinetics of [ 14C]vinylidene chloride (VDC)in rats were undertaken to characterize the disposition of the inhaled chemical and to aid in assessing the hazard associated with VDC exposure. Male rats normally fed or previously fasted for 18 hr were exposed to 10 or 200 ppm of [ 14C]VDC vapor for 6 hr, and the elimination of 14C activity was followed for 72 hr after exposure. Following the exposure to 10 ppm of [ 14C]VDC, approximately 98% of the acquired body burden of [ 14C]VDC was metabolized to nonvolatile metabolites of VDC. Fasting had no effect on the metabolism of [ 14C]VDC at this exposure concentration. However, after exposure to 200 ppm of VDC only 92 to 96% of the body burden was metabolized with fasted rats showing a reduced capacity to metabolize VDC at this exposure concentration. Fasted rats exposed to 200 ppm of [ 14C]VDC sustained liver and kidney damage, which was not observed in fed rats at this exposure level or in any rats at 10 ppm. Centrilobular hepatic necrosis in fasted rats exposed to 200 ppm of [ 14C]VDC was associated with an increase in covalently bound 14C activity in the liver over that of fed rats. Two major urinary metabolites of VDC were identified as N-acetyl- S-(2-hydroxyethyl)cysteine and thiodiglycolic acid, indicating that a major pathway for detoxification of VDC is via conjugation with liver glutathione (GSH).