Evaluation of novel markers of exposure and biological response to 1,4-dioxane

项目摘要/摘要 1，4-二恶烷(1，4-DX)是一种合成化学品，历史上曾用作氯化溶剂的稳定剂和 目前用于一系列消费和个人护理产品。超过五分之一的美国公众饮酒 供水中含有可检测到的1，4-DX水平，测试的饮用水样本中约有7% 超过0.35μg/L的联邦癌症风险水平。 在纽约长岛拿骚和萨福克县的地下水中观察到，那里75%的人口 1，4-DX浓度超过0.35μg/L的水源。此外，标准市政 处理系统在去除1，4-DX方面效果不佳，使其在饮用水供应中得以持续存在。这个 美国环境保护署(EPA)已将1，4-DX列为高度优先的化学品，并将其归类为 根据实验动物研究的证据，它可能是一种人类致癌物质，主要基于 对肝脏的影响。尽管环境中的高流行率和潜在的人类健康风险，但有一个 缺乏人体接触和健康数据。我们将应用新的方法来评估1，4-DX的暴露 和共生污染物(如挥发性有机化合物1，1-二氯乙烷(DCA)， 三氯乙烯(TCE)和1，1，1-三氯乙烷(TCA))在纽约长岛(我们的 主要研究区)和北卡罗来纳州的开普费雷河流域(次要研究区)。我们将使用我们的 新开发的基于高灵敏质谱学的方法用于1，4-DX暴露的评估 水样和血样。此外，我们将评估接触1，4-DX和CO-2之间的关系。 使用非靶向和靶向两种方法检测血液中内源性代谢物和脂类的污染物和水平 代谢组学。生物监测和代谢组学的使用为评估早期暴露提供了强大的工具 以及疾病临床表现前几年的生物学变化。我们提出了一种横截面 关于长岛(有许多超级基金站点可能导致饮酒污染的地区)的研究 含1，4-DX)的水)评估人类对1，4-DX的暴露，并评估两者之间的关系 环境和生物暴露指标，二)评价1，4-DX暴露的时间变异性和 通过比较来自美国不同水源(地下水)的两个不同地区的数据，得出代谢物水平 在纽约州和北卡罗来纳州的地表水中)，以及iii)评估1，4-DX暴露与 生物反应，特别是对肝脏毒性和致癌作用。这个项目将极大地增强我们的 了解饮用水和饮用水中1，4-DX(及其共生污染物)的暴露程度 对人类健康的潜在影响。研究结果将为政策制定者提供科学依据 1，4-DX浓度标准指南，并为超级基金研究计划中的研究人员提供 使用新的工具来检测环境中的危险物质，以及新的技术 补救措施。

Project Summary/Abstract 1,4-Dioxane (1,4-DX) is a synthetic chemical historically used as a stabilizer of chlorinated solvents and currently used in a range of consumer and personal care products. Over one-fifth of the US public drinking water supply contains detectable levels of 1,4-DX, and approximately 7% of drinking water samples tested exceed the federal cancer risk level of 0.35 μg/L. Widespread contamination of drinking water has been observed in groundwater in Nassau and Suffolk Counties of Long Island, New York, where 75% of population have water sources with 1,4-DX concentrations exceeding 0.35 μg/L. Furthermore, standard municipal treatment systems are ineffective at removing 1,4-DX, enabling its persistence in drinking water supplies. The US Environmental Protection Agency (EPA) has designated 1,4-DX as a “high priority” chemical and classified it as a probable human carcinogen based on evidence from experimental animal studies, primarily based on effects on the liver. Despite the high prevalence in the environment and potential human health risks, there is a paucity of human exposure and health data. We will apply novel approaches to evaluate exposure to 1,4-DX and co-occurring contaminants (such as the volatile organic compounds 1,1-dichloroethane (DCA), trichloroethylene (TCE), and 1,1,1-trichloroethane (TCA)) in two communities: Long Island, New York (our primary study area) and Cape Fear River Watershed, North Carolina (secondary study area). We will use our newly developed, highly sensitive mass spectrometry-based assay for assessment of exposure to 1,4-DX in water and blood samples. In addition, we will evaluate associations between exposure to 1,4-DX and co- contaminants and levels of endogenous metabolites and lipids in blood using both untargeted and targeted metabolomics. The use of biomonitoring and metabolomics provide powerful tools to assess early exposures and biological changes in the years preceding clinical manifestation of disease. We propose a cross-sectional study on Long Island (an area with many Superfund sites potentially contributing to contamination of drinking water with 1,4-DX) to i) assess human exposure to 1,4-DX and evaluate the relationship between environmental and biological exposure indicators, ii) evaluate temporal variability of exposure to 1,4-DX and metabolite levels by comparing data from two different US regions with different water sources (ground water in NY and surface water in NC), and iii) evaluate the relationship between 1,4-DX exposure and metabolites of biological responses particularly for liver toxicity and carcinogenesis. This project will greatly enhance our understanding of the extent of exposure to 1,4-DX (and its co-occurring contaminants) in drinking water and the potential for human health effects. The results will provide scientific evidence for policy makers to set guidelines for concentration standards for 1,4-DX and provide researchers in the Superfund Research Program with new tools to detect hazardous substances in the environment as well as novel technologies for remediation.