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Non-targeted approaches to screen new markers of chemical exposure from human matrices: application and challenges regarding sample preparation and data processing

机译:从人矩阵筛选新型化学曝光标记的非目标方法:关于样品准备和数据处理的应用和挑战

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Our environment is vector of human exposure to hundred thousands of chemicals. This opened view of the chemical space contaminating the environment-food-human continuum is today supported by advanced chemical profiling instrumentation opening the door to holistic sample characterisation. One particular issue in this context is related to the early warning detection of emerging chemicals. Non-targeted screening (NTS) approaches are new valuable strategies aiming to detect unknown markers of exposure without any a priori. These screening approaches are associated to important expectations and promises, but also major challenges for scientists, particularly concerning sample preparation and data processing. In the frame of the workpackage WP16 "emerging chemicals" of the Human Biomonitoring for European Union project (HBM4EU, EU H2020), the present work proposes a first focus on these two last components, in order to deterrnine which are suitable for NTS. The halogenated compounds were the selected chemicals for this study, because of their persistence in the environment and their toxicological concern. The first step consisted in developing appropriated sample preparation protocols for various human matrices of interest, especially accessible matrices from mother-child cohorts, namely breast milk, meconium or placenta. The main lines of these investigations will be presented and discussed, with a particular - but not exclusive - focus on placenta analysis. The challenging sample preparation issues will be described, as well as the final analytical strategy which was a combination of a Bligh and Dyer extraction[l] followed by a LC-HESI-HRMS Q-Orbitrap analysis. The second step consisted in developing a user-friendly application, HaloSeeker[2], based on isotopic patterns and mass defect, to highlight chlorinated and brominated clusters, resulting in several chemical formulae assigned as a finalised output. This first proof of concept finally illustrates the real capability and complexity of these NTS approaches in support of human biomonitoring and environmental-health researches. [1]doi.org/10.1139/o59-099 [2]doi/10.1021/acs.analchem.8b05103
机译:我们的环境是人类暴露于数十万化学品的矢量。这一打开了污染了环境 - 食品 - 人类连续体的化学空间的看法,今天通过先进的化学品分析仪表,开启了整体样本表征。在这种情况下,一个特殊问题与新兴化学品的预警检测有关。非目标筛查(NTS)方法是新的宝贵策略,其目的是在没有任何先验的情况下检测未知的曝光标记。这些筛选方法与重要的期望和承诺相关,对科学家们的主要挑战,特别是关于样品准备和数据处理。在欧洲联盟项目的人体生物监唱的WP16“新兴化学品”的框架中(HBM4EU,EU H2020),本作者提出了第一次关注这两个最后一部分,以便达到适合NTS的替代。卤代化合物是本研究的所选化学品,因为它们在环境中持续存在和毒理学关注。第一步组成,用于开发针对各种人类血管的适当样品制剂方案,特别是来自母儿队列的母婴群,即母乳,胎儿或胎盘的可接近矩阵。这些调查的主要线条将被提出和讨论,特别是但不排他性 - 专注于胎盘分析。将描述具有挑战性的样品制备问题,以及最终的分析策略,其是Bligh和染色萃取[L]的组合,然后是LC-Hesi-HRMS Q-orbitrap分析。基于同位素图案和质量缺陷,将第二步包括在开发用户友好型应用中,以突出氯化和溴化簇,产生几种分配的化学式作为最终输出的化学式。这一概念证明最终阐述了这些NTS支持人体生物监测和环境健康研究的真实能力和复杂性。 [1] Doi.org/10.1139/059-099 [2] DOI / 10.1021 / ACS.ANALCHEM.8B05103

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