Project 1 - Cardiometabolic Injury due to VOCs

项目总结 该项目的总体目标是评估与超级基金相关的动荡风险敞口的影响 有机化合物(VOCs)对心脏代谢性疾病的潜在条件 会导致糖尿病、心血管疾病和肝脏疾病。三氯乙烯等VOCs， 苯、丙烯醛、甲醛、二甲苯和丁二烯是最令人担忧的主要化学品。 超级基金网站和大量先前的工作表明，对VOC的敞口可能有多种 对健康的不利影响。尽管如此，接触VOCs的水平是否与 与超级基金站点相邻的社区可能会对心脏新陈代谢健康状况产生不利影响 未知。我们对接触不同VOCs的动物进行的广泛研究表明，慢性 暴露在低剂量VOCs中会升高血压，造成血管损伤，加速 动脉粥样硬化，并引发肝病。然而，VOCs的心脏代谢风险 未评估和询问暴露-反应关系的纵向数据是 失踪。因此，为了评估VOCs施加的CMD风险，我们将检验以下假设 VOCs加重/诱发血管和肝脏功能障碍，导致一系列事件 这增加了CMD的风险。为了评估接触挥发性有机化合物的影响，我们将调查1200名居民 杰斐逊县，包括那些住在超级基金网站邻近地区的人，比如李的 Lane和Distiller Farm，以及高VOC排放，如Rubbertown社区。 在每个参与者中，我们将通过测量肝细胞的标志物动脉僵硬来评估CMD的风险 死亡，以及一套指示糖尿病、心血管疾病和肝脏风险的生物标志物 疾病。人群水平VOC暴露及其与CMD相关关系的研究 入院率和死亡率，我们将建立一个VOC监测网来测量VOC 并监测生活污水的尿液挥发性有机化合物 代谢物。我们将在三年内每隔一个月监测一次废水，并评估其程度 哪些人群水平的暴露估计反映了环境空气VOC水平和个人水平 暴露(目标1)，以及这些估计如何与人群和个人层面的慢性疾病有关 风险。为了获得纵向数据，我们将检查CMD级数并确定 个人水平和社区水平的VOC暴露与血管和 肝功能和心脏代谢风险的其他指标。这将有助于我们评估VOC如何 暴露和/或靠近超级基金地点的居住位置会影响CMD的风险， 过高的风险不同于城市社区背景VOC暴露所带来的风险。 我们预计，该项目的完成将导致量化风险模型的发展 以及对可归因于住宅VOC暴露的额外CMD风险的严格估计。

PROJECT SUMMARY The overall goal of this project is to assess the impact of exposure to Superfund-relevant volatile organic compounds (VOCs) on cardiometabolic disease, the underlying conditions that contributes to diabetes, cardiovascular and liver diseases. VOCs such as trichloroethylene, benzene, acrolein, formaldehyde, xylene and butadiene are major chemicals of concern at most Superfund sites and extensive previous work suggests the exposure to VOC could have a variety of adverse health effects. Nevertheless, whether exposure to VOCs at levels relevant to neighborhood adjacent to Superfund sites could adversely affect cardiometabolic health remains unknown. Our extensive studies with animal exposed to different VOCs suggest that chronic exposure to low dose VOCs could increase blood pressure, inflict vascular injury, accelerate atherosclerosis, and induce liver disease. Nevertheless, the cardiometabolic risk of VOCs has not been evaluated and longitudinal data to interrogate exposure-response relationships are missing. Hence, to assess CMD risk imposed by VOCs, we will test the hypothesis that exposure to VOCs exacerbates/induces vascular and hepatic dysfunction leading to a cascade of events that increase CMD risk. To assess the impact of VOC exposures, we will examine 1200 residents of Jefferson County, including those who live in areas adjacent to Superfund sites such as Lee’s Lane and Distiller Farm, as well as high VOC emission, such as the Rubbertown neighborhood. In each participant, we will assess CMD risk by measuring arterial stiffness, marker of hepatocyte death, as well as suite of biomarkers indicative of risk for diabetes, cardiovascular and liver diseases. To determine population-level VOC exposure and its relationship with CMD-related hospital admissions and mortality, we will establish a network of VOC monitors to measure VOC levels throughout Jefferson County and monitor domestic wastewater for urinary VOC metabolites. We will monitor wastewater every other month for 3 years, and assess the extent to which population-level exposure estimates reflect ambient air VOC levels and individual-level exposure (Aim 1), and how these estimates relate to population-level and individual-level CMD risk. To obtain longitudinal data, we will examine CMD progression and determine the association between individual-level and community-level VOC exposures with vascular and hepatic function and other indices of cardiometabolic risk. This will help us in assessing how VOC exposure and/or residential proximity to Superfund sites affects the risk of CMD and this excessive risk differs from that imposed by background VOC exposures in urban neighborhood. We expect that completion of this project will lead to the development of quantitative risk models and rigorous estimates of the additional CMD risk attributable to residential VOC exposures.