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吸入后2-氨基蒽在大鼠体内的分布、滞留及转归

Distribution, retention, and fate of 2-aminoanthracene in rats after inhalation.

作者信息

Mitchell C E, Henderson R F, McClellan R O

出版信息

Toxicol Appl Pharmacol. 1984 Aug;75(1):52-9. doi: 10.1016/0041-008x(84)90075-9.

Abstract

The distribution, retention, and fate of 2[3H]aminoanthracene (2-AA) were determined in male Fischer-344 rats after inhalation exposure (70 micrograms/liter; activity mass median diameter = 2.1 micron) for 30 min. Radioactivity was found in the turbinates, trachea, lungs, liver, kidneys, and gastrointestinal tract 20 min after exposure. Lower quantities of radioactivity were found in fat, brain, testes, and muscle. Inhaled 2-AA was excreted predominantly in feces (80%). The remaining 2-AA was excreted in urine. Organic soluble radioactivity was released from urinary conjugates after treatment of urine with acid and with beta-glucuronidase. This result suggests that glucuronides of both ring- and N-hydroxy-2-AA were excreted. The remaining radioactivity was water soluble and accounted for approximately one-half of the total urinary radioactivity. The organic soluble radioactivity found after hydrolysis indicated that inhaled 2-AA is extensively metabolized by rats after inhalation and excreted as conjugated metabolites. Eighty-three percent of orally administered material was absorbed into the body from the GI tract; thus, material cleared by mucociliary action after inhalation would contribute to total body burden. 2-AA, a nitrogen substituted polycyclic aromatic hydrocarbon (PAH), was very similar to other PAHs in its rapid distribution throughout the body and in its route of excretion after inhalation.

摘要

在雄性Fischer - 344大鼠吸入暴露(70微克/升;活性质量中值直径 = 2.1微米)30分钟后,测定了2[³H]氨基蒽(2 - AA)的分布、滞留和归宿。暴露20分钟后,在鼻甲、气管、肺、肝、肾和胃肠道中发现了放射性。在脂肪、脑、睾丸和肌肉中发现的放射性量较低。吸入的2 - AA主要通过粪便排出(80%)。其余的2 - AA通过尿液排出。用酸和β - 葡萄糖醛酸酶处理尿液后,有机可溶性放射性从尿结合物中释放出来。这一结果表明,环羟基和N - 羟基2 - AA的葡萄糖醛酸结合物都被排出。其余的放射性是水溶性的,约占总尿放射性的一半。水解后发现的有机可溶性放射性表明,吸入的2 - AA在大鼠吸入后被广泛代谢,并以结合代谢物的形式排出。口服给药的物质83%从胃肠道吸收进入体内;因此,吸入后通过粘液纤毛作用清除的物质会增加全身负担。2 - AA是一种氮取代的多环芳烃(PAH),在其在体内的快速分布及其吸入后的排泄途径方面与其他PAHs非常相似。

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