Discovery of novel environmental chemicals in a diverse population of maternal-infant pairs

项目摘要/摘要 在子宫内暴露于多种环境化学物质已被证明在整个过程中都会对健康造成不利影响 寿命，导致不良生育结局、神经发育缺陷、糖尿病和肥胖，以及 癌症。然而，限制我们表征和解决发展健康风险能力的一个关键数据差距是 缺乏关于新生儿接触大量工业化学品的数据，这些化学品用于 我们。在美国，超过90%的大量生产和使用的化学品(25,000磅/年)是 在大规模的人体生物监测研究中没有测量到。此外，目前的生物监测方法 需要事先选择化合物以开发和验证有针对性的分析方法；缺乏 工业或商业产品中化学品使用数据的缺失阻碍了准确预测 在近8000种高使用量的化学品中，美国人最有可能接触到这种化学品。为了应对这些挑战， 我们的项目将推进一项创新的、以发现为导向的研究项目，该项目使用液相色谱学- 四极飞行时间质谱仪(LC-QTOF/MS)对 人口统计中约700种环境有机酸(EOA)的存在和共生 母婴配对的不同群体。我们还将演示此屏幕如何通知 选择化学品进行有针对性的分析方法开发，同时解决#年的人口差异问题 EOA暴露和母体血清水平在子宫暴露中准确反映的程度。我们专注于 因为它们更容易被我们的LC-QTOF/MS检测到，因此是我们新发现的一个很好的模型 接近。此外，它们在结构上与已知会对发展产生不利影响的化学物质相似，因此 潜在的健康风险。使用LC-QTOF/MS，我们将筛选300名匹配的脐带血和产妇血清 从种族和经济多元化的人群中收集的样本，用于约700个EOA。使用LC- QTOF/MS结果，我们将确定10种有可能广泛接触人类和 人口统计和母婴接触差异。我们将开发LC-MS/MS方法来确认和 量化这10个EOA，并评估LC-QTOF/MS屏幕的性能。我们会比较脐带血 拉美裔与非拉美裔白人、美国出生与外国出生以及低收入人群脐带血清中10种EOA的水平 与高收入亚组的对比，并评估母婴对之间暴露的差异。我们的 以发现为导向的可疑筛查将开创一种生物监测方法，对目标化学品进行优先排序 基于它们在人类群体中被检测的可能性的方法开发。这也将是一个 对于其他研究人员来说，这是非常宝贵的资源，他们可能会查询它以了解产前期间的新化学暴露情况 句号。最后，我们还将对有针对性的方法清单作出实质性贡献 环境化学品，并产生关于脆弱和易感人群的关键新暴露数据 这是确定有害化学品的健康风险并为预防提供信息的基础。

Project Summary/Abstract In utero exposure to multiple environmental chemicals has been shown to adversely impact health throughout the lifespan, leading to adverse birth outcomes, neurodevelopmental deficits, diabetes and obesity, and cancer. Yet, a key data gap limiting our ability to characterize and address developmental health risks is the lack of data on the extent to which neonates are exposed to the vast array of industrial chemicals used in the US. Over 90% of the chemicals manufactured and used in high volumes (>25,000 pounds/year) in the US are not measured in large-scale human biomonitoring studies. Further, the current biomonitoring approach requires a priori selection of compounds for which to develop and validate targeted analytical methods; the lack of data on chemical use in industrial or commercial products hinders the ability to accurately anticipate to which of the almost 8000 high use chemicals the US population is most likely exposed. To address these challenges, our project will advance an innovative, discovery-driven research project using liquid chromatography- quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) to perform a General Suspects Screen for the presence and co-occurrence of approximately 700 Environmental Organic Acids (EOAs) in a demographically diverse population of maternal-neonate pairs. We will also demonstrate how this screen can inform the selection of chemicals for targeted analysis methods development while addressing demographic disparities in EOA exposure and the extent to which maternal serum levels accurately reflect in utero exposures. We focus on EOAs because they are more easily detected by our LC-QTOF/MS and thus are a good model for our novel approach. Also, they are structurally similar to chemicals known to adversely impact development and thus are of potential health risk. Using LC-QTOF/MS, we will screen 300 matched umbilical cord and maternal serum samples, collected from a racially and economically diverse population, for ~ 700 EOAs. Using the LC- QTOF/MS results, we will identify 10 EOAs with potential for widespread human exposure and for demographic and maternal-neonatal exposure disparities. We will develop LC-MS/MS methods to confirm and quantify these 10 EOAs, and evaluate the performance of the LC-QTOF/MS screen. We will compare umbilical cord serum levels of the 10 EOAs in Hispanic versus non-Hispanic white, US– versus foreign-born, and low– versus high-income subgroups, and assess differences in exposures between maternal-fetal pairs. Our discovery-driven, suspect screen will pioneer a biomonitoring approach that prioritizes chemicals for targeted method development based on their likelihood of detection in the human population. It will also be an invaluable resource for other researchers who may query it for novel chemical exposures during the prenatal period. Finally, we will also make substantial contributions to the inventory of targeted methods for environmental chemicals and generate critical new exposure data on vulnerable and susceptible populations that is foundational to characterize and inform prevention of health risks from harmful chemicals.