Effect-based human biomonitoring of complex chemical mixtures using high-throughput target screening and in vitro bioassays

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URI: http://hdl.handle.net/10900/158607
http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-1586071
http://nbn-resolving.org/urn:nbn:de:bsz:21-dspace-1586077
http://dx.doi.org/10.15496/publikation-99939
Dokumentart: PhDThesis
Date: 2024-10-30
Language: English
Faculty: 7 Mathematisch-Naturwissenschaftliche Fakultät
Department: Chemie
Advisor: Escher, Beate (Prof. Dr.)
Day of Oral Examination: 2024-09-03
DDC Classifikation: 333.7 - Natural resources and energy
500 - Natural sciences and mathematics
540 - Chemistry and allied sciences
610 - Medicine and health
Other Keywords: In vitro
Mischungen
Chemikalien
Neurotoxizität
neurotoxicity
chemicals
mixtures
In vitro
License: http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=de http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=en
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Abstract:

Human biomonitoring is a valuable tool for investigating and understanding the human chemical exposome and its association to human health. Current approaches are mainly focusing on a small subset of already well-studied chemicals and neglect the fact that humans are exposed to a diverse set of complex chemical mixtures. This thesis introduced the concept of effect-based human biomonitoring (EB-HBM), which combines chemical exposure assessment, cell-based in vitro bioassays and in silico models to assess the composition and effects of human-relevant complex chemical mixtures. The developed and optimized models and methods were demonstrated with a case study on neurotoxic mixture effects of chemicals extracted from the blood of 624 pregnant women from a German cohort study. Chemical mixtures were extracted by a holistic two-step extraction method. Over 1,000 chemicals in this large number of samples could be analyzed with a new workflow for automated analysis and quantification. Effect drivers were identified by mixture experiments and modeling. The mixture toxicity concept of concentration addition turned out to valid for predicting the effects of the recreated real-life mixtures. The use of high-throughput target screening combined with cell-based bioassays bears great potential to improve human biomonitoring and provide a novel approach to include mixtures in epidemiological studies.

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