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人工甜味剂肟V的代谢与毒理学研究

Metabolic and toxicologic study of an artificial sweetener, oxime V.

作者信息

Mitoma C, Acton E M, DeGraw J I, Thomas D W

出版信息

Drug Chem Toxicol. 1985;8(4):195-206. doi: 10.3109/01480548509038645.

Abstract

Metabolic disposition and subchronic oral toxicologic studies were conducted on a new synthetic sweetener, Oxime V. Based on radioactivity assay, the compound was readily absorbed and metabolized. Excretion was nearly quantitative 48 hours after dosing the rat, dog, and rhesus monkey. The major metabolites were formed by oxidation and reduction of the cyclohexadiene ring, oxidation of the aldoxime and dimethyl ether moieties followed by conjugation with glycine, thiomethylation of the ring, and O-glucuronidation of the aldoxime. A two-month feeding study was conducted with male adult rats. The average consumption of Oxime V was 396.5 mg/kg per day by rats fed a diet containing 0.6% of the test compound. No treatment related histopathologic lesion was observed in the liver, kidney, spleen, and testes. The liver weight relative to the body weight and serum bilirubin level were increased.

摘要

对一种新型合成甜味剂肟V进行了代谢处置和亚慢性口服毒理学研究。基于放射性测定,该化合物易于吸收和代谢。在给大鼠、狗和恒河猴给药48小时后,排泄几乎是定量的。主要代谢产物是由环己二烯环的氧化和还原、醛肟和二甲醚部分的氧化,随后与甘氨酸结合、环的硫甲基化以及醛肟的O-葡萄糖醛酸化形成的。对成年雄性大鼠进行了为期两个月的喂养研究。喂食含0.6%受试化合物日粮的大鼠,肟V的平均摄入量为每天396.5毫克/千克。在肝脏、肾脏、脾脏和睾丸中未观察到与治疗相关的组织病理学病变。肝脏重量相对于体重增加,血清胆红素水平升高。

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