Understanding the metabolism, distribution, and elimination of chemical xenobiotics is often critical to an appreciation of their toxic effects. Extrapolation of results from animal testing to possible human health effects requires knowledge of metabolic pathways and in vivo kinetic behavior. In vestigation of mechanistic aspects of metabolic processes allows greater understanding of how metabolism of a xenobiotic might lead either to detoxification or to a reactive metabolite with greater toxicity. As more is learned about mecahnisms of metabolism, more accurate predictions of possible metabolic pathways for new compounds should be possible. This group carried out studies on oxazepam (OXM), ethoxyquin (EQN), and 4-methylimidazole (4MI) in the past year. The metabolism and elimination of OXM, a Valium analog, in F344 rats has been studies and compared to mice. Sulfate conjugation was more prevalent in rats than mice. A dihydrodiol metabolite was characterized. Animals were also pretreated with OXM in feed for 14 days. Urinary elimination was increased by pretreatment for females but not males. Sulfate conjugation was decreased by pretreatment in both sexes. The metabolism and disposition of EQN, an antioxidant, in both rats and mice indicates that it is readily metabolized in both species. EQN was raiply cleared from blood, reaching limits of detection in less than one hour. Toxicokinetic studies on 4MI, a chemical intermediate used in the chemical and pharmaceutical industries, have shown it to be rapidly absorbed and nearly completely excreted in urine with minimal metabolism.
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