Disposition of [1,2-14C] vinyl chloride in the rat

Rats were exposed to [1,2-¹⁴C] vinyl chloride in a closed system at initial concentrations below 100 ppm. When the system was occupied by 3 rats, a half-life of vinyl chloride in the system's atmosphere of 1.13 ± 0.12 h was observed. The volume of the system was 10.3 l. Calculation of the clearance of vinyl chloride from the system revealed that about 40% of inspired vinyl chloride is absorbed by lung. Therefore, changes in respiration did not influence uptake of vinyl chloride.Uptake of vinyl chloride by the rats was completely blocked by acute pretreatment with potent inhibitors of cytochrome-P-450-dependent microsomal drug metabolism (i.e., by 35 mg/kg 3-bromophenyl-4(5)-imidazole or 50 mg/kg 6-nitro-1,2,3-benzothiadiazole in 0.6 ml/kg DMSO). A weaker inhibition was observed after dosing SKF 525 A or 5,6-dimethyl-1,2,3-benzothiadiazole (50 mg/kg in 0.6 ml/kg DMSO). Metyrapone did not cause inhibition.Uptake of vinyl chloride was increased by pretreatment with DDT and, to a lesser extent, with clotrimazol. No significant stimulation of uptake was observed after pretreatment with phenobarbital, 3-methylcholanthrene, rifampicin, or chronic ethanol treatment.Immediately after exposure, highest radioactivity levels were observed in liver and kidney. The radioactive metabolites of ¹⁴C-vinyl chloride were rapidly excreted, largely by the kidneys. Excretion of radioactivity in the urine was 69.4 ± 2.6% within 24 h.