ACUTE ACRYLONITRILE INTOXICATION--ANTIDOTAL ASSESSMENT

急性丙烯腈中毒——解毒评估

• 批准号: 3254459
• 负责人: FREDERICK W BENZ
• 金额: $ 11.06万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3254459
• 关键词: antidotes; biomarker; blood chemistry; chemical binding; cyanides; cytochrome P450; dosage; drug screening /evaluation; environmental toxicology; glutathione; glutathione analog; high performance liquid chromatography; inhibitor /antagonist; laboratory rat; macromolecule; nitrites; oxidoreductase inhibitor; pharmacology; plastics; poisoning; scintillation spectrometry; thiosulfate

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.

丙烯腈是一种广泛用于生产的化学品 合成纤维、塑料和橡胶。 丙烯腈是一种 实验中具有急性致死作用的活性化学物质 动物。 意外接触丙烯腈的人类死亡 已被报道。 目前的工业卫生习惯可能会限制 工人在正常职业期间接触丙烯腈 程序。 然而，意外接触高浓度可能会 严重影响参与人员的健康 丙烯腈的生产、运输和最终使用。 在 一旦发生大量丙烯腈意外泄漏事件， 普通民众的健康可能会受到影响。 丙烯腈 可氧化代谢为氰化物，约为其十倍 按摩尔比计算，其毒性比母体分子更大。 然而， 由于其与硫醇基团的高化学反应性 体中，母体丙烯腈分子也被认为是 有毒的。 因此丙烯腈是一把双刃剑和解毒剂 措施必须同时考虑氰化物成分和 其毒性作用的“其他”成分。 不幸的是， 目前推荐的丙烯腈中毒解毒疗法 只专注于氰化物中毒的治疗。 我们的 目的是模拟急性真皮丙烯腈暴露 同时测量三个重要的生化标志物 与丙烯腈毒性有关。 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。 选择解药 因为他们有能力改善这些标记物 将评估丙烯腈毒性。 意义 这项工作是我们希望能够将有利的 解毒剂对生化标志物的疗效影响 作为急性丙烯腈中毒的解毒剂。 这样 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作用就会实现。 在 此外，我们预计会有更有效的解毒剂或 急性丙烯腈中毒的解毒剂组合 从这些研究中浮现出来。