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Comparative metabolism and disposition of ethoxyquin in rat and mouse. I. Disposition.

1. The biological fate of the antioxidant [3-14C]ethoxyquin (EQ) was investigated in the male F344 rat and the B6C3F1 mouse following either p.o. or i.v. administration. 2. The disposition of single doses up to 25 mg/kg was similar in the rat and mouse. About 90% of a total dose was excreted in urine and faeces within 24 h post-dosing. In contrast, no more than 60% of a higher dose of 250 mg/kg was excreted within 24 h following p.o. administration. 3. Metabolism of EQ was rapid in both the rat and mouse following either p.o. or i.v. administration. Little or no parent compound was detected in cumulative 24-h excreta. 5. EQ-derived radioactivity bioaccumulated in some tissues following repeated exposure to rat of either 25 or 250 mg/kg by gavage. However, the fold-increases in concentrations of EQ-derived radioactivity in tissues following repeated administration of the higher dose were generally less than those observed following repeated administration of the lower dose. Repeated high dose administration may overcome delayed gastric emptying (observed following single dose administration of 250 mg/kg) and/or lead to auto-induction of EQ metabolism.