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首页> 外文期刊>Journal of applied toxicology >Species and gender differences in the metabolism and distribution of tertiary amyl methyl ether in male and female rats and mice after inhalation exposure or gavage administration.
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Species and gender differences in the metabolism and distribution of tertiary amyl methyl ether in male and female rats and mice after inhalation exposure or gavage administration.

机译:吸入暴露或管饲法给药后,雄性和雌性大鼠和小鼠中叔戊基甲基醚代谢和分布的物种和性别差异。

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摘要

Tertiary amyl methyl ether (TAME) is a gasoline fuel additive used to reduce emissions. Understanding the metabolism and distribution of TAME is needed to assess potential human health issues. The effect of dose level, duration of exposure and route of administration on the metabolism and distribution of TAME were investigated in male and female F344 rats and CD-1 mice following inhalation or gavage administration. By 48 h after exposure, >96% of the administered radioactivity was expired in air (16-71%) or eliminated in urine and feces (28-72%). Following inhalation exposure, mice had a two- to threefold greater relative uptake of [(14)C]TAME compared with rats. Metabolites were excreted in urine of rats and mice that are formed by glucuronide conjugation of tertiary amyl alcohol (TAA), oxidation of TAA to 2,3-dihydroxy-2-methylbutane and glucuronide conjugation of 2,3-dihydroxy-2-methylbutane. A saturation in the uptake and metabolism of TAME with increased exposure concentration was indicated by a decreased relative uptake of total [(14)C]TAME equivalents and an increase in the percentage expired as volatiles. A saturation of P-450 oxidation of TAA was indicated by a disproportional decrease of 2,3-dihydroxy-2-methylbutane and its glucuronide conjugate with increased exposure concentration.
机译:叔戊基甲基醚(TAME)是用于减少排放的汽油燃料添加剂。需要了解TAME的代谢和分布,以评估潜在的人类健康问题。在雄性和雌性F344大鼠和CD-1小鼠中,通过吸入或管饲法研究了剂量水平,暴露时间和给药途径对TAME代谢和分布的影响。暴露后48小时,> 96%的放射性在空气中消失(16-71%),或在尿液和粪便中消失(28-72%)。吸入暴露后,与大鼠相比,小鼠的[(14)C] TAME相对摄入量高2-3倍。代谢物在大鼠和小鼠的尿中排泄,这些代谢物是由葡萄糖醛酸化物结合叔戊醇(TAA),TAA氧化为2,3-二羟基-2-甲基丁烷和葡萄糖醛酸化物结合2,3-二羟基-2-甲基丁烷形成的。随着总[(14)C] TAME当量的相对吸收降低和作为挥发物而到期的百分数的增加,表明暴露浓度增加时,TAME的摄取和代谢达到饱和。随着暴露浓度的增加,2,3-二羟基-2-甲基丁烷及其葡糖醛酸苷共轭物的不成比例减少表明了TAA的P-450氧化饱和。

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