Academic Journal
Evaluating the Endocrine-Disrupting and Oxidative Stress Potential of a 50-Component Human-Relevant Complex Chemical Mixture Using In Vitro Tests.
| Τίτλος: | Evaluating the Endocrine-Disrupting and Oxidative Stress Potential of a 50-Component Human-Relevant Complex Chemical Mixture Using In Vitro Tests. |
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| Συγγραφείς: | Engelhardt J; Department of Environmental Science, Stockholm University, Stockholm, Sweden., Struwe N; School of Science and Technology, Örebro University, Örebro, Sweden., Jansson A; Department of Environmental Science, Stockholm University, Stockholm, Sweden.; Department of Chemical Engineering, Royal Institute of Technology (KTH), Stockholm, Sweden.; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Kos VM; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Larsson M; School of Science and Technology, Örebro University, Örebro, Sweden., Weiss JM; Department of Environmental Science, Stockholm University, Stockholm, Sweden. |
| Πηγή: | Journal of applied toxicology : JAT [J Appl Toxicol] 2026 Jun; Vol. 46 (6), pp. 2003-2018. Date of Electronic Publication: 2025 Nov 29. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: John Wiley And Sons Country of Publication: England NLM ID: 8109495 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1099-1263 (Electronic) Linking ISSN: 0260437X NLM ISO Abbreviation: J Appl Toxicol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Original Publication: [Philadelphia, Pa. : Heyden & Son, c1981- |
| Ιατρικοί όροι (MeSH): | Endocrine Disruptors*/toxicity , Oxidative Stress*/drug effects , Complex Mixtures*/toxicity , Environmental Pollutants*/toxicity, Flame Retardants/toxicity ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Polychlorinated Biphenyls/toxicity ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Humans ; Cell Line |
| Περίληψη: | Humans are chronically exposed to mixtures of environmental contaminants. Exposure to endocrine-disrupting chemicals (EDCs) contributes to increased health impairment observed globally. This study aimed to evaluate the endocrine-disruptive and oxidative stress potential of a human-relevant, complex chemical mixture in vitro. By testing chemical class subgroup mixtures, the identity of toxicological drivers and mixture additivity could be investigated. A 50-component mixture was compiled based on Swedish human blood concentrations (xHBC), consisting of six subgroup mixtures: polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (PCB mixture), brominated flame retardants (BFR mixture), per- and polyfluoroalkyl substances (PFAS mixture), pesticide mixture, synthetic phenolic contaminants (phenol mixture), and phthalate mixture. These were tested in four chemically activated luciferase gene expression (CALUX) assays: dioxin responsive (DR-), estrogen receptor α (ERα-), androgen receptor. (AR-), and nuclear factor erythroid 2-related factor 2 (Nrf2)-CALUX, along with an adipocyte cell assay. The total mixture caused significant agonistic activity in DR- and ER-, and antagonistic activity in AR-CALUX at 0.1-15 xHBC, depending on the assay. Mixture additivity was assessed in ERα-, DR-, and anti-AR-CALUX using subgroup mixtures and the concentration addition (CA) model. The total mixture followed the CA model in ERα-, anti-AR- and DR-CALUX. The toxicological drivers of these activities were mainly the PCB and phenol mixture. A significant increase in differentiated adipocytes was observed at 100 xHBC. These results raise concerns regarding potential health effects on the endocrine system. The additive effects at human-relevant concentrations observed in this study motivate considering mixtures in regulatory contexts to protect the well-being of future generations. (© 2025 The Author(s). Journal of Applied Toxicology published by John Wiley & Sons Ltd.) |
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| Grant Information: | 2018-02264 Swedish Research Council FORMAS; 2019-00375 Swedish Research Council FORMAS; August Emil Wilhelm Smitts stipendie- och understödsstiftelse; 20190098 KK Foundation |
| Contributed Indexing: | Keywords: CALUX; chemical mixtures; concentration additivity; endocrine‐disrupting chemicals; environmental contaminants; human blood concentrations; in vitro; oxidative stress |
| Substance Nomenclature: | 0 (Endocrine Disruptors) 0 (Complex Mixtures) 0 (Environmental Pollutants) 0 (Flame Retardants) 0 (Receptors, Androgen) DFC2HB4I0K (Polychlorinated Biphenyls) 0 (NF-E2-Related Factor 2) 0 (Estrogen Receptor alpha) |
| Entry Date(s): | Date Created: 20251129 Date Completed: 20260503 Latest Revision: 20260909 |
| Update Code: | 20260909 |
| PubMed Central ID: | PMC13136407 |
| DOI: | 10.1002/jat.70011 |
| PMID: | 41317044 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1099-1263 |
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| DOI: | 10.1002/jat.70011 |