STRATEGY TO IDENTIFY NONADDITIVE RESPONSE TO CHEMICAL

描述 低水平接触有机磷酸酯（OP）可能会影响 农业工人、士兵和普通民众的健康。 目前的研究技术需要从 高剂量暴露与低剂量的普通暴露之间的差异。 生化 分析的指标是最有希望的指标， 在环境相关剂量下多次接触化学品的影响。 加速器质谱（AMS）具有灵敏度和精确度， 定量同位素的组织剂量或生物标志物的阿托摩尔水平 标记的化合物的精确度<5%。 AMS将量化神经细胞 亚ppm同位素标记的OP农药标记物的膜结合 暴露。 其他酯类的化学混合物，也可用于环境 将同时应用，以确定这些多个 暴露于不同的酯引起非加性效应的结合， 标记OP。小鼠将多次暴露于多达四种化合物， 并且神经中的OP结合将被测定长达三天。 整体 目标是展示一种识别化学混合物的新策略， 在相关的低暴露下具有非加性生化反应， 消除目前的战略，依赖于不确定的外推， 高剂量、单一化合物数据。 如果该策略被证明是有用的， 并对化学混合物接触进行有意义的筛查， 为公众提供更好的卫生标准和法规， 具体职业。

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.