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STRATEGY TO IDENTIFY NONADDITIVE RESPONSE TO CHEMICAL

识别化学品非添加剂反应的策略

基本信息

批准号：
6055971
负责人：
JOHN S VOGEL
金额：
$ 24.79万
依托单位：
UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-15 至 2000-08-31
项目状态：
已结题

项目摘要

DESCRIPTION Low level exposures to organophosphate (OP) esters are suspected to impact the health of agricultural workers, soldiers, and the general population. Current techniques of study require extrapolation of imprecise data from high dose exposures to the low doses of usual exposures. Biochemical markers of analyses are the most promising indicators of response to the effects of multiple chemical exposures at environmentally relevant doses. Accelerator mass spectrometry (AMS) has the sensitivity and precision to quantify attomole levels of tissue doses or biomarkers of isotopically labeled compounds to precisions of <5%. AMS will quantify the nerve cell membrane binding of an isotope labeled OP pesticide marker at sub-ppm exposures. Chemical mixtures of other esters, also at environmentally realistic doses, will be concurrently applied to determine if these multiple exposures to different esters cause non-additive effects in the binding of the marker OP. Mice will be exposed to up to four compounds in multiples, and OP binding in nerves will be assayed for up to three days. The overall goal is to demonstrate a new strategy for identifying chemical mixtures that have non-additive biochemical response at relevant low exposures in order to eliminate the current strategies that depends on uncertain extrapolation of high dose, single compound data. If the strategy proves useful, more rapid and meaningful screening of chemical mixture exposures can be implemented to provide better health advisories and regulations for the general public and for specific occupations.

描述低水平暴露于有机磷(OP)酯可能会影响农业工人、士兵和普通民众的健康。目前的研究方法需要从不精确的数据中推断高剂量暴露于通常的低剂量暴露。生化分析标记是最有希望的反应指标与环境有关的剂量的多次化学品暴露的影响。加速器质谱仪(AMS)的灵敏度和精密度组织剂量或生物标记物的同位素定量水平标记化合物的精密度为&lt；5%。AM将对神经细胞进行量化同位素标记有机磷农药标志物在亚百万分率下的膜结合曝光。其他酯的化学混合物，也在环境方面实际剂量，将同时应用以确定这些倍数暴露于不同的酯可引起结合的非相加效应。记分器动作。小鼠将被多次暴露在多达四种化合物中，神经中的OP结合将被检测长达三天。整体而言目标是展示一种识别化学混合物的新策略在相关的低暴露下有非加性的生化反应，以便消除当前依赖于不确定外推的战略高剂量，单一化合物数据。如果这个策略被证明是有效的，那么就会更快并对化学混合物暴露进行有意义的筛查，以为公众提供更好的健康建议和法规，并对于特定的职业。