DISPOSITION OF 2-METHYLIMIDAZOLE IN RATS

2-Methylimidazole (2-MI), widely used as a chemical intermediate, is a lso present in cigarette smoke and may form in food and forage as a re sult of ammoniation of simple sugars. 2-MI has been shown to be neurot oxic in several animal species and to alter serum levels of T-3, T-4, and thyroid-stimulating hormone (TSH) in the rat, apparently leading t o hyperplasia of thyroid follicular cells. In order to better characte rize 2-MI-induced toxicity, the disposition of[2-C-14]-2-MI has been i nvestigated following po administration of either 5, 50, or 150 mg/kg to male F344 rats. Excretion data indicated that absorption of 2-MI wa s both rapid and proportional to dose in the range studied. Approximat ely 90% of the total dose was eliminated in urine within 24 h. Most of the remaining C-14 was excreted in feces and as expired (CO2)-C-14. E xcretion data were similar following iv administration of 5 mg/kg. Lit tle or no enterohepatic circulation of compound occurred since biliary excretion of 2-MI-derived C-14 was negligible. Approximately 70% of t he C-14 excreted in urine, following all dosing, consisted of parent c ompound. High-performance liquid chromatography (HPLC) chromatograms f or all treatment groups were similar, indicating that metabolism of 2- MI in rats was not affected by dose or route of administration.