Evaluating the Endocrine‐Disrupting and Oxidative Stress Potential of a 50‐Component Human‐Relevant Complex Chemical Mixture Using In Vitro Tests
Year: 2025
Type: article
Abstract: 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.
Source: Journal of Applied Toxicology
DOI: 10.1002/jat.70011
Authors: Josefin Engelhardt, Nathalie Struwe, Annika Jansson, Vesna Munic Kos, Maria Larsson, Jana M. Weiss
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,940
Awards: Risk modeling of mixtures of endocrine disrupting chemicals relevant to human exposure, using zebrafish (Danio rerio) embryo as model organism (RiskMix), G4361603874, G5659103075, The evaluation of in vitro skeletal muscle models for the assessment of metabolism disrupting chemicals contributing to insulin resistance, G712881263
OpenAlex ID: W4416816577