Evaluating the Endocrine-Disrupting and Oxidative Stress Potential of a 50-Component Human-Relevant Complex Chemical...

Area of Science:

• Environmental Health Sciences
• Toxicology
• Endocrinology

Background:

• Humans face chronic exposure to complex mixtures of environmental contaminants.
• Endocrine-disrupting chemicals (EDCs) are linked to widespread health impairments.
• Understanding mixture toxicity is crucial for public health risk assessment.

Purpose of the Study:

• To evaluate the in vitro endocrine-disruptive and oxidative stress potential of a human-relevant chemical mixture.
• To identify toxicological drivers and assess mixture additivity using chemical subgroup analysis.
• To investigate effects on nuclear receptors and adipocyte differentiation.

Main Methods:

• A 50-component mixture based on Swedish human blood concentrations (xHBC) was created, including PCBs, BFRs, PFAS, pesticides, phenols, and phthalates.
• Chemically activated luciferase gene expression (CALUX) assays were used for dioxin (DR-), estrogen receptor (ERα-), androgen receptor (AR-), and Nrf2 pathways.
• An adipocyte cell assay was conducted; mixture additivity was assessed using the concentration addition (CA) model.

Main Results:

• The total mixture exhibited significant agonistic activity in DR- and ERα-CALUX assays and antagonistic activity in AR-CALUX at 0.1-15 xHBC.
• The total mixture followed the concentration addition model for ERα-, anti-AR-, and DR-CALUX assays, indicating additive effects.
• Polychlorinated biphenyls (PCBs) and phenol mixtures were identified as primary toxicological drivers; increased adipocyte differentiation occurred at 100 xHBC.

Conclusions:

• Complex environmental chemical mixtures demonstrate additive endocrine-disruptive effects at human-relevant concentrations.
• The findings highlight the need to consider mixture effects in regulatory risk assessments.
• These results raise concerns for endocrine system health and the well-being of future generations.