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首页> 外文期刊>Journal of applied toxicology >Characterization of metabolites and disposition of tertiary amyl methyl ether in male F344 rats following inhalation exposure.
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Characterization of metabolites and disposition of tertiary amyl methyl ether in male F344 rats following inhalation exposure.

机译：吸入暴露后的雄性F344大鼠的代谢产物表征和叔戊基甲基醚的处置。

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摘要

Tertiary amyl methyl ether (TAME) is a fuel additive used to reduce carbon monoxide in automobile emissions. Because of the potential for human exposure, this study was conducted to develop methods for the characterization and quantitation of metabolites in expired air and excreta of rats exposed to a mixture of [(13)C]- and [(14)C]TAME ([2,3,4-(13)C]- and [2-(14)C]2-methoxy-2-methylbutane). The distribution of TAME in rats was determined following inhalation exposure, and TAME-derived metabolites were characterized in expired air and urine. Male rats were exposed for 6 h via nose-only inhalation to 2500 ppm [(14)C/(13)C]TAME, and expired air, urine and feces were collected for up to 7 days. Over 95% of the total recovered radioactivity was excreted by 48 h after exposure. Recovered radioactivity was expired as organic volatiles (44%) and (14)CO(2) (3%) and excreted in urine (51%) and feces (1%). Both TAME and its metabolite tertiary amyl alcohol (TAA) accounted for >/=90% of the radiolabel in expired air 0-8 h following exposure termination. Three major urinary metabolites of TAME were identi fi ed: (1) a direct glucuronide conjugate of TAA; (2) a product of oxidation at the methylene carbon of TAA (2,3-dihydroxy-2-methylbutane); (3) a glucuronide conjugate of metabolite 2. Metabolite 1 accounted for most of the TAME-derived metabolites excreted 0-8 h following exposure termination. Further metabolic products of TAA (metabolites 2 and 3) accounted for most of the excreted TAME-derived metabolites at later time points.
机译：叔戊基甲基醚（TAME）是一种燃料添加剂，用于减少汽车尾气中的一氧化碳。由于可能暴露于人体，因此进行了这项研究，以开发出表征和定量暴露于[[13] C]-和[（14）C] TAME混合物的大鼠的呼出气和排泄物中代谢产物的方法（ [2,3,4-（13）C]-和[2-（14）C] 2-甲氧基-2-甲基丁烷）。吸入后确定TAME在大鼠中的分布，并在呼出的空气和尿液中表征TAME衍生的代谢产物。雄性大鼠仅通过鼻子吸入暴露于2500 ppm [（14）C /（13）C] TAME，暴露6小时，收集呼出的空气，尿液和粪便长达7天。暴露后48小时，全部回收的放射性的95％以上被排泄。恢复的放射性以有机挥发物（44％）和（14）CO（2）（3％）的形式到期，并在尿液（51％）和粪便（1％）中排出。在暴露终止后0-8小时，TAME及其代谢物叔戊醇（TAA）占呼出空气中放射性标记的> / = 90％。确定了TAME的三种主要尿代谢产物：（1）TAA的直接葡糖醛酸苷结合物; （2）在TAA的亚甲基碳（2,3-二羟基-2-甲基丁烷）上的氧化产物; （3）代谢物2的葡萄糖醛酸结合物。代谢物1占暴露终止后0-8小时排泄的大部分TAME衍生代谢物。在以后的时间点，TAA的其他代谢产物（代谢物2和3）占TAME衍生的大部分代谢产物。

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