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In Vitro Bioassay Evidence for Chemical Mixture Propagation from the Environment to Humans.

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Τίτλος: In Vitro Bioassay Evidence for Chemical Mixture Propagation from the Environment to Humans.
Συγγραφείς: Escher B; Department of Cell Toxicology, Helmholtz Centre for Environmental Research - UFZ, Leipzig 04318, Germany.; Department of Geosciences, Eberhard Karls University of Tübingen, Schnarrenbergstr. 94-96, 72076 Tübingen, Germany.; German Center for Child and Adolescent Health (DZKJ), partner site Leipzig/Dresden, Leipzig 04103, Germany., Scholze M; Centre for Pollution Research and Policy, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, U.K., Margalef M; Amsterdam Institute for Life and Environment, Faculty of Science, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands., König M; Department of Cell Toxicology, Helmholtz Centre for Environmental Research - UFZ, Leipzig 04318, Germany., Valente MJ; National Food Institute, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark., Hamers T; Amsterdam Institute for Life and Environment, Faculty of Science, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands., Renko K; German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R), 10589 Berlin, Germany., Audebert M; Toxalim, Université de Toulouse, INRAE,INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 31062 Toulouse, France.; PrediTox, 31100 Toulouse, France., Lee J; Department of Cell Toxicology, Helmholtz Centre for Environmental Research - UFZ, Leipzig 04318, Germany., Khoury L; PrediTox, 31100 Toulouse, France., Cenijn P; Amsterdam Institute for Life and Environment, Faculty of Science, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands., Ma Y; National Food Institute, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark., Treschow AF; National Food Institute, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark., Toms LM; School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia., Rørbye C; Department of Obstetrics and Gynaecology, Hvidovre University Hospital, 2650 Hvidovre, Denmark., Braun G; Department of Cell Toxicology, Helmholtz Centre for Environmental Research - UFZ, Leipzig 04318, Germany., Motteau S; LABERCA, Oniris, INRAE, 44307 Nantes, France., Antignac JP; LABERCA, Oniris, INRAE, 44307 Nantes, France., Dervilly G; LABERCA, Oniris, INRAE, 44307 Nantes, France., Lamoree M; Amsterdam Institute for Life and Environment, Faculty of Science, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands., Vinggaard AM; National Food Institute, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
Πηγή: Environmental science & technology [Environ Sci Technol] 2026 Jun 16; Vol. 60 (23), pp. 16498-16513. Date of Electronic Publication: 2026 Jun 02.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: American Chemical Society Country of Publication: United States NLM ID: 0213155 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5851 (Electronic) Linking ISSN: 0013936X NLM ISO Abbreviation: Environ Sci Technol Subsets: MEDLINE
Imprint Name(s): Publication: Washington DC : American Chemical Society
Original Publication: Easton, Pa. : American Chemical Society, c1967-
Ιατρικοί όροι (MeSH): Complex Mixtures*/analysis, Animals ; Humans ; Biological Assay
Περίληψη: Complex mixtures of organic chemicals extracted from representative but not directly related environmental samples (wastewater, surface water, fish), food items (drinking water, fish, milk) and human blood were tested in 22 in vitro bioassays targeting pathways associated with neurodevelopmental and reproductive health. Extraction methods were optimized to extract common chemicals across matrices capturing both persistent and nonpersistent, neutral and charged organic chemicals─albeit with some bias toward more hydrophilic chemicals over highly hydrophobic chemicals. Most bioassay end points─except genotoxicity─were responsive, with strongest effects observed higher up the food chain in fish and humans. Experimental mixture effects of 24 chemicals quantified in these extracts conformed to the mixture prediction model of concentration addition in the six most responsive bioassays, namely neurite outgrowth inhibition, mitochondrial membrane potential inhibition, transthyretin protein binding, sodium-iodide symporter inhibition and androgen receptor antagonism. Designed mixtures explained little of total bioactivity, indicating that many of the thousands of unannotated molecular features detected by nontarget analysis contribute to mixture effects. Preliminary effect-based trigger (EBT) values defined for water and food by extrapolation from safe levels of individual chemicals indicate no immediate health risks at these average contamination levels. The high complexity and multivalent bioactivity of these mixtures on neurodevelopmental and reproductive pathways necessitate further toxicological scrutiny.
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Contributed Indexing: Keywords: adverse outcome pathway; concentration addition; iceberg modeling; in vitro bioassay; mixture effects; new approach methodologies
Substance Nomenclature: 0 (Complex Mixtures)
Entry Date(s): Date Created: 20260602 Date Completed: 20260616 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC13290017
DOI: 10.1021/acs.est.6c00908
PMID: 42227708
Βάση Δεδομένων: MEDLINE
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  Data: In Vitro Bioassay Evidence for Chemical Mixture Propagation from the Environment to Humans.
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  Data: <searchLink fieldCode="AU" term="%22Escher+B%22">Escher B</searchLink>; Department of Cell Toxicology, Helmholtz Centre for Environmental Research - UFZ, Leipzig 04318, Germany.; Department of Geosciences, Eberhard Karls University of Tübingen, Schnarrenbergstr. 94-96, 72076 Tübingen, Germany.; German Center for Child and Adolescent Health (DZKJ), partner site Leipzig/Dresden, Leipzig 04103, Germany.<br /><searchLink fieldCode="AU" term="%22Scholze+M%22">Scholze M</searchLink>; Centre for Pollution Research and Policy, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, U.K.<br /><searchLink fieldCode="AU" term="%22Margalef+M%22">Margalef M</searchLink>; Amsterdam Institute for Life and Environment, Faculty of Science, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.<br /><searchLink fieldCode="AU" term="%22König+M%22">König M</searchLink>; Department of Cell Toxicology, Helmholtz Centre for Environmental Research - UFZ, Leipzig 04318, Germany.<br /><searchLink fieldCode="AU" term="%22Valente+MJ%22">Valente MJ</searchLink>; National Food Institute, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.<br /><searchLink fieldCode="AU" term="%22Hamers+T%22">Hamers T</searchLink>; Amsterdam Institute for Life and Environment, Faculty of Science, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.<br /><searchLink fieldCode="AU" term="%22Renko+K%22">Renko K</searchLink>; German Federal Institute for Risk Assessment (BfR), German Centre for the Protection of Laboratory Animals (Bf3R), 10589 Berlin, Germany.<br /><searchLink fieldCode="AU" term="%22Audebert+M%22">Audebert M</searchLink>; Toxalim, Université de Toulouse, INRAE,INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 31062 Toulouse, France.; PrediTox, 31100 Toulouse, France.<br /><searchLink fieldCode="AU" term="%22Lee+J%22">Lee J</searchLink>; Department of Cell Toxicology, Helmholtz Centre for Environmental Research - UFZ, Leipzig 04318, Germany.<br /><searchLink fieldCode="AU" term="%22Khoury+L%22">Khoury L</searchLink>; PrediTox, 31100 Toulouse, France.<br /><searchLink fieldCode="AU" term="%22Cenijn+P%22">Cenijn P</searchLink>; Amsterdam Institute for Life and Environment, Faculty of Science, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.<br /><searchLink fieldCode="AU" term="%22Ma+Y%22">Ma Y</searchLink>; National Food Institute, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.<br /><searchLink fieldCode="AU" term="%22Treschow+AF%22">Treschow AF</searchLink>; National Food Institute, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.<br /><searchLink fieldCode="AU" term="%22Toms+LM%22">Toms LM</searchLink>; School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia.<br /><searchLink fieldCode="AU" term="%22Rørbye+C%22">Rørbye C</searchLink>; Department of Obstetrics and Gynaecology, Hvidovre University Hospital, 2650 Hvidovre, Denmark.<br /><searchLink fieldCode="AU" term="%22Braun+G%22">Braun G</searchLink>; Department of Cell Toxicology, Helmholtz Centre for Environmental Research - UFZ, Leipzig 04318, Germany.<br /><searchLink fieldCode="AU" term="%22Motteau+S%22">Motteau S</searchLink>; LABERCA, Oniris, INRAE, 44307 Nantes, France.<br /><searchLink fieldCode="AU" term="%22Antignac+JP%22">Antignac JP</searchLink>; LABERCA, Oniris, INRAE, 44307 Nantes, France.<br /><searchLink fieldCode="AU" term="%22Dervilly+G%22">Dervilly G</searchLink>; LABERCA, Oniris, INRAE, 44307 Nantes, France.<br /><searchLink fieldCode="AU" term="%22Lamoree+M%22">Lamoree M</searchLink>; Amsterdam Institute for Life and Environment, Faculty of Science, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.<br /><searchLink fieldCode="AU" term="%22Vinggaard+AM%22">Vinggaard AM</searchLink>; National Food Institute, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22American+Chemical+Society%22">American Chemical Society </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>0213155 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1520-5851 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%220013936X%22">0013936X </searchLink><i>NLM ISO Abbreviation: </i>Environ Sci Technol <i>Subsets: </i>MEDLINE
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  Data: Complex mixtures of organic chemicals extracted from representative but not directly related environmental samples (wastewater, surface water, fish), food items (drinking water, fish, milk) and human blood were tested in 22 in vitro bioassays targeting pathways associated with neurodevelopmental and reproductive health. Extraction methods were optimized to extract common chemicals across matrices capturing both persistent and nonpersistent, neutral and charged organic chemicals─albeit with some bias toward more hydrophilic chemicals over highly hydrophobic chemicals. Most bioassay end points─except genotoxicity─were responsive, with strongest effects observed higher up the food chain in fish and humans. Experimental mixture effects of 24 chemicals quantified in these extracts conformed to the mixture prediction model of concentration addition in the six most responsive bioassays, namely neurite outgrowth inhibition, mitochondrial membrane potential inhibition, transthyretin protein binding, sodium-iodide symporter inhibition and androgen receptor antagonism. Designed mixtures explained little of total bioactivity, indicating that many of the thousands of unannotated molecular features detected by nontarget analysis contribute to mixture effects. Preliminary effect-based trigger (EBT) values defined for water and food by extrapolation from safe levels of individual chemicals indicate no immediate health risks at these average contamination levels. The high complexity and multivalent bioactivity of these mixtures on neurodevelopmental and reproductive pathways necessitate further toxicological scrutiny.
– Name: Ref
  Label: References
  Group: RefInfo
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