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

摘要

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