Neurological Effects of Environmental Styrene and BTEX Exposure in a Gulf of Mexico Cohort

摘要 苯乙烯在职业水平上是神经毒性的，但在环境水平上得到的研究很少，因为 普通民众，尽管受到广泛的接触。我们的研究小组发现，年平均环境 苯乙烯水平与神经功能和症状呈负相关，包括 视觉、感觉和前庭功能。普通人群中接触苯乙烯的主要途径是 吸入工业废气和车辆废气、烟草烟雾和建筑材料的尾气。它是生产出来的 来自石油衍生的苯和乙苯，这解释了为什么美国一半以上的苯乙烯生产 发生在海湾国家的石油和天然气作业附近。苯、乙苯、甲苯和二甲苯(即， BTEX)在职业水平上也具有神经毒性。这项拟议的研究意义重大，因为实际上 没有数据描述大多数这些神经毒物在一般人群水平上的安全性，尽管 曝光。本研究的目的是研究苯乙烯和苯系物的急性和慢性神经毒性 在与普通民众相关的水平上。我们的中心假设是，即使在一般的人口水平上， 环境中较高的苯乙烯/苯系物水平与周围神经和神经行为功能下降有关 以及神经症状的增加。我们将在海湾地区23370名具有良好特征的前瞻性队列中测试这一点 参加2011-2013年海湾长期跟踪研究的州居民--一项社会经济学 弱势群体，医疗服务不足，种族多元化，健康状况不明 差距。这一人群的平均血液中的苯乙烯水平是在 一般人群，但远低于职业接触者通常观察到的~25倍的高水平 人口。我们有关于所有队列成员的广泛信息，从登记和后续面试， 关于人口、生活方式、职业和健康因素；地理编码的居住史；测量的血液 965名队列成员在登记的最后一年中的苯乙烯和苯系物水平；以及广泛的 3403名成员在2-4年后接受周围神经功能和神经行为测试 招生。我们建议：(1)生成时间和空间参考的高分辨率环境(AIR) 海湾地区6年随访期内的苯乙烯和苯系物浓度，(2)评估估计 环境中的苯乙烯和苯系物浓度与测量的血液中的苯系物和苯系物的浓度，以及(3)确定 单独和混合接触苯系物和苯系物与神经系统症状的关系 以及神经行为和周围神经功能，这是其他神经毒性空气污染物的原因。这 这项研究具有创新性，因为我们将是第一个在普通人群中研究苯乙烯的神经毒性的人 我们将使用最先进的空气质量暴露数据融合方法来实现这一点，这些方法以前没有 已应用于苯乙烯或苯系物。这项研究对公共健康的影响很高，因为接触到 苯乙烯和苯系物广泛存在，众所周知，这些化学物质在职业水平上具有神经毒性。

Abstract Styrene is neurotoxic at occupational levels, but has received little study at environmental levels experienced by the general population, despite widespread exposure. Our study team has found that annual average ambient styrene levels are adversely associated with neurologic function and symptoms, including decrements in visual, sensory, and vestibular function. Exposure to styrene in the general population occurs primarily through inhalation of industrial and vehicle emissions, tobacco smoke, and off-gassing of building materials. It is produced from petroleum-derived benzene and ethylbenzene, which explains why over half of US styrene production occurs near oil and gas operations in the Gulf states. Benzene, ethylbenzene, toluene, and xylenes (i.e., BTEX) are also neurotoxic at occupational levels. The proposed study is significant because there are virtually no data describing the safety of most of these neurotoxicants at general population levels, despite widespread exposure. The objective of this study is to investigate the acute and chronic neurotoxicity of styrene and BTEX at levels relevant to the general population. Our central hypothesis is that, even at general population levels, higher ambient styrene/BTEX levels are associated with reduced peripheral nerve and neurobehavioral function and increased neurologic symptoms. We will test this in a prospective, well-characterized cohort of 23,370 Gulf state residents enrolled in the Gulf Long-Term Follow-up Study in 2011-2013—a socioeconomically disadvantaged, medically underserved, and racially diverse population with significant unexplained health disparities. This population has average blood styrene levels 2-3 times higher than those observed in the general population, but much lower than the ~25-fold higher levels typically observed in occupationally exposed populations. We have extensive information on all cohort members, from enrollment and follow-up interviews, on demographic, lifestyle, occupational, and health factors; geocoded residential histories; measured blood levels of styrene and BTEX from 965 cohort members during the last year of enrollment; and results of extensive peripheral neurologic function and neurobehavioral tests administered to 3,403 members 2-4 years after enrollment. We propose to: (1) Generate high resolution temporally- and spatially-referenced ambient (air) styrene and BTEX concentrations in the Gulf region over a 6 year follow-up period, (2) Evaluate estimated ambient styrene and BTEX concentrations against measured blood styrene and BTEX levels, and (3) Determine associations of styrene and BTEX exposures, both individually and as a mixture, with neurologic symptoms and neurobehavioral and peripheral neurologic function, accounting for other neurotoxic air pollutants. This study is innovative because we will be the first to investigate the neurotoxicity of styrene at general population levels and we will do so using state-of-the-art air quality exposure data fusion methods that have not previously been applied to styrene or BTEX. The Public Health Impact of this research is high because exposure to styrene and BTEX is widespread and these chemicals are known to be neurotoxic at occupational levels.