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Disposition of 2-methylimidazole in rats.

2-Methylimidazole (2-MI), widely used as a chemical intermediate, is also present in cigarette smoke and may form in food and forage as a result of ammoniation of simple sugars. 2-MI has been shown to be neurotoxic in several animal species and to alter serum levels of T3, T4, and thyroid-stimulating hormone (TSH) in the rat, apparently leading to hyperplasia of thyroid follicular cells. In order to better characterize 2-MI-induced toxicity, the disposition of [2-(14)C]-2-MI has been investigated following p.o. administration of either 5, 50, or 150 mg/kg to male F344 rats. Excretion data indicated that absorption of 2-MI was both rapid and proportional to dose in the range studied. Approximately 90% of the total dose was eliminated in urine within 24 h. Most of the remaining 14C was excreted in feces and as expired 14CO2. Excretion data were similar following i.v. administration of 5 mg/kg. Little or no enterohepatic circulation of compound occurred, since biliary excretion of 2-MI-derived 14C was negligible. Approximately 70% of the 14C excreted in urine, following all dosing, consisted of parent compound. High-performance liquid chromatography (HPLC) chromatograms for all treatment groups were similar, indicating that metabolism of 2-MI in rats was not affected by dose or route of administration.