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大鼠吸入偶氮二甲酰胺的代谢情况

The fate of inhaled azodicarbonamide in rats.

作者信息

Mewhinney J A, Ayres P H, Bechtold W E, Dutcher J S, Cheng Y S, Bond J A, Medinsky M A, Henderson R F, Birnbaum L S

出版信息

Fundam Appl Toxicol. 1987 Apr;8(3):372-81. doi: 10.1016/0272-0590(87)90086-8.

Abstract

Azodicarbonamide (ADA) is widely used as a blowing agent in the manufacture of expanded foam plastics, as an aging and bleaching agent in flour, and as a bread dough conditioner. Human exposures have been reported during manufacture as well as during use. Groups of male F344/N rats were administered ADA by gavage, by intratracheal instillation, and by inhalation exposure to determine the disposition and modes of excretion of ADA and its metabolites. At 72 hr following gavage, 30% of the administered ADA was absorbed whereas following intratracheal instillation, absorption was 90%. Comparison between groups of rats exposed by inhalation to ADA to achieve body burdens of 24 or 1230 micrograms showed no significant differences in modes or rates of excretion of [14C]ADA equivalents. ADA was readily converted to biurea under physiological conditions and biurea was the only 14C-labeled compound present in excreta. [14C]ADA equivalents were present in all examined tissues immediately after inhalation exposure, and clearance half-times on the order of 1 day were evident for all tissues investigated. Storage depots for [14C]ADA equivalents were not observed. The rate of buildup of [14C]ADA equivalents in blood was linearly related to the lung content as measured from rats withdrawn at selected times during a 6-hr inhalation exposure at an aerosol concentration of 25 micrograms ADA/liter. In a study extending 102 days after exposure, retention of [14C]ADA equivalents in tissues was described by a two-component negative exponential function. The results from this study indicate that upon inhalation, ADA is rapidly converted to biurea and that biurea is then eliminated rapidly from all tissues with the majority of the elimination via the urine.

摘要

偶氮二甲酰胺(ADA)在制造发泡塑料时被广泛用作发泡剂,在面粉中用作陈化和漂白剂,以及作为面包面团调节剂。据报道,在制造和使用过程中均有人员接触到ADA。对雄性F344/N大鼠分组进行灌胃、气管内滴注和吸入暴露,以确定ADA及其代谢产物的处置和排泄方式。灌胃后72小时,所给予的ADA有30%被吸收,而气管内滴注后,吸收量为90%。对吸入ADA以达到24或1230微克体内负荷的大鼠组进行比较,结果显示[14C]ADA当量的排泄方式和速率没有显著差异。在生理条件下,ADA很容易转化为双脲,双脲是排泄物中唯一存在的14C标记化合物。吸入暴露后,所有检查的组织中立即都有[14C]ADA当量,并且所有研究的组织清除半衰期约为1天。未观察到[14C]ADA当量的储存库。在气溶胶浓度为25微克ADA/升的6小时吸入暴露期间,在选定时间处死的大鼠中,血液中[14C]ADA当量的积累速率与肺含量呈线性相关。在一项暴露后长达102天的研究中,组织中[14C]ADA当量的滞留情况可用双组分负指数函数描述。这项研究的结果表明,吸入后,ADA迅速转化为双脲,然后双脲迅速从所有组织中消除,大部分通过尿液排出。

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