ACUTE ACRYLONITRILE INTOXICATION--ANTIDOTAL ASSESSMENT

丙烯腈是一种广泛用于生产 合成纤维、塑料和橡胶。 丙烯腈是一种 在实验中具有急性致死作用的反应性化学品 动物 意外接触丙烯腈的人类死亡 已经被报道了。 目前的工业卫生做法可以限制 丙烯腈作业工人在正常作业期间的接触情况 程序. 然而，意外暴露于高水平， 严重影响个人的健康参与 丙烯腈的生产、运输和最终用途。 在 一个大的意外释放丙烯腈的事件，即使是 普通民众的健康可能受到影响。 丙烯腈 可以氧化代谢成氰化物， 在摩尔基础上比母体分子毒性更大。 然而，在这方面， 由于其与硫醇基的高化学反应性， 身体，母体丙烯腈分子也被认为是 有毒 因此丙烯腈是一把双刃剑， 措施必须考虑到氰化物成分和 其毒性作用的"其他“成分。 可惜 目前推荐的丙烯腈中毒解毒疗法 专注于氰化物中毒的管理 我们 目的是模拟急性皮肤丙烯腈暴露， 同时测定三种重要生化指标 与丙烯腈中毒有关 这些标记包括 组织氰化物水平，丙烯腈与组织不可逆结合 大分子和组织谷胱甘肽水平。 选择解毒剂 因为他们能够改善这些标志物中的每一个 将评价丙烯腈毒性。 的意义 这项工作是，我们希望能够将有利的 解毒剂对药效生化指标的影响 作为急性丙烯腈中毒的解毒剂。 以这种方式 对各种影响的相对重要性的一些见解 丙烯腈在体内的毒性将被认识到。 在 此外，我们预计，更有效的解毒剂或 急性丙烯腈中毒的解毒剂组合将 从这些研究中产生。

Acrylonitrile is a chemical widely used in the production of synthetic fibers, plastics and rubber. Acrylonitrile is a reactive chemical with an acute lethal action in experimental animals. Deaths in humans accidentally exposed to acrylonitrile have been reported. Current industrial hygiene practices can limit the exposure of workers to acrylonitrile during normal occupational procedures. However, accidental exposures to high levels can acutely affect the health of individuals involved in the production, transportation, and end use of acrylonitrile. In the event of a large accidental release of acrylonitrile, even the health of the general populace could be affected. Acrylonitrile can be oxidatively metabolized to cyanide which is some ten times more toxic than the parent molecule on a molar basis. However, because of its high chemical reactivity with thiol groups in the body, the parent acrylonitrile molecule is also thought to be toxic. Thus acrylonitrile is a double edged sword and antidotal measures must take into account both the cyanide component and the 'other' component(s) of its toxic action. Unfortunately, the currently recommended antidotal therapy for acrylonitrile poisoning focuses solely on the management of cyanide intoxication. Our objective is to mimic an acute dermal acrylonitrile exposure and simultaneously measure three important biochemical markers associated with acrylonitrile toxicity. These markers include tissue cyanide levels, irreversible acrylonitrile binding to tissue macromolecules and tissue glutathione levels. Antidotes selected for their ability to ameliorate each of these markers of acrylonitrile toxicity will be evaluated. The significance of this work is that we hope to be able to correlate the favorable effects of the antidotes on the biochemical markers with efficacy as antidotes for acute acrylonitrile intoxication. In this way some insight into the relative importance of the various effects of acrylonitrile in the body on toxicity will be realized. In addition, we anticipate that more effective antidotes or combinations of antidotes for acute acrylonitrile intoxication will emerge from these studies.