Drug Metabolism and Disposition 1987-01-01

Comparative metabolism and disposition of 1-chloro- and 3-chloro-2-methylpropene in rats and mice.

B I Ghanayem, L T Burka

文献索引：Drug Metab. Dispos. 15(1) , 91-6, (1987)

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摘要

A recent 2-year carcinogenicity study found that gavage administration of 3-chloro-2-methylpropene (CMP), containing 5% 1-chloro-2-methylpropene (dimethylvinyl chloride, DMVC), caused forestomach neoplasms in rats and mice. Similar chronic studies revealed that DMVC caused forestomach neoplasms in both rats and mice; neoplasms of the nasal and oral cavities were observed in rats but not in mice. In the current studies we have investigated the metabolic basis of these differences. Daily doses of 150 mg/kg of 2-[14C]DMVC or 2-[14C]CMP were administered to rats for 1, 2, or 4 consecutive days. One daily dose of 150 mg/kg of DMVC was administered to mice. Both DMVC and CMP were rapidly metabolized; however, CMP was cleared at a slightly lower rate. Rats exhaled approximately 25 and 10% of the DMVC and CMP as CO2, respectively. Mice exhaled 25% of the DMVC as CO2. Rats expired 30% of the administered DMVC unchanged in the 24 hr after dosing compared to only 7% of the administered CMP. Mice expired 5% of the administered DMVC in the same time period. This observation may explain the occurrence of tumors in the nasal and oral cavities of rats treated with DMVC but not in rats treated with CMP or in mice treated with DMVC in 2-year carcinogenicity studies. The 24-hr urinary excretion in rats was 35% of the administered DMVC compared to 58% of CMP. Mice excreted 47% of the administered DMVC in 24 hr in the urine. An unusual urinary metabolite of DMVC, 2-amino-6-methyl-4-thia-5-heptene-1,7-dioic acid, was identified.(ABSTRACT TRUNCATED AT 250 WORDS)