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From toxic mixtures to disease

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While synthetic organic chemicals in consumer products, industry and pesticides improve our quality of life, their ubiquitous presence in air, water, food leads to human uptake and may pose significant health risks. ToxSick will transform human biomonitoring by assessing the adverse effects of real-life chemical mixtures through a panel of in vitro bioassays combined with targeted screening of hundreds of chemicals.
Rarely do individual chemicals drive toxicity; rather, the mixture itself represents the true risk, necessitating a shift from identifying single culprits to quantifying mixture effects. To identify which chemical mixtures trigger non-communicable diseases (NCD), we have identified molecular initiating events and cellular key events in adverse outcome pathways that lead to NCDs and are susceptible to disruption by chemicals. Corresponding in vitro bioassays will be miniaturized, multiplexed, and validated for compatibility with blood extracts to enable high-throughput testing of thousands of human blood extracts, as well as realistic mixtures and individual chemicals.
Given the ubiquity of chemical exposure, understanding the exposome in healthy populations is essential before linking it to disease outcomes. Characterizing extracts of pooled blood samples of healthy young adults in the German Environmental Specimen Bank will help reveal longitudinal time trends in chemical burdens since 1985. A mother-child cohort spanning pregnancy to puberty, comprising over 6000 plasma samples, will test platform scalability and serve as a reference for epidemiological investigations. Analyses of blood from adult monozygotic twins with divergent phenotypes will further disentangle genetic from environmental drivers of disease. This new approach of effect-based human biomonitoring will integrate with clinical studies of the German Centre for Child and Adolescent Health, targeting allergies, metabolic disorders, and neurodevelopmental outcomes in children.

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Gastgebende Einrichtung

HELMHOLTZ-ZENTRUM FUR UMWELTFORSCHUNG GMBH - UFZ
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€ 2 499 787,00
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PERMOSERSTRASSE 15
04318 Leipzig
Deutschland
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Sachsen Leipzig Leipzig
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