Mixture Toxicity in Human Health: Integrating One Health, Exposomics, and Modern Risk Assessment Strategies.

Area of Science:

• Environmental Health Sciences
• Toxicology
• Regulatory Science

Background:

• Human and environmental health face critical threats from combined exposures to diverse chemical toxicants.
• Existing risk assessments inadequately predict additive, synergistic, or antagonistic effects of chemical mixtures, leading to underestimated health risks.

Purpose of the Study:

• To synthesize current scientific understanding of toxicant interactions and critique global regulatory approaches to chemical mixtures.
• To advocate for a paradigm shift in chemical risk assessment and regulation.

Main Methods:

• Review of current scientific literature on toxicant interactions and mixture toxicity.
• Analysis of major regulatory frameworks (e.g., TSCA, REACH) and their limitations in addressing chemical mixtures.
• Examination of case studies involving PFAS, heavy metals, and pesticide mixtures.
• Synthesis of emerging tools (exposomics, computational toxicology) and holistic frameworks (One Health).

Main Results:

• Conventional single-substance risk assessments systematically underestimate health risks associated with combined chemical exposures.
• Major regulatory frameworks continue to assess chemicals in isolation, despite robust evidence of mixture toxicity.
• Pioneering regulatory efforts in Canada (cumulative risk assessments) and the EU (mixture assessment factors) offer models for progress.

Conclusions:

• A paradigm shift integrating mixture toxicity assessments into regulatory frameworks is essential.
• Reforms should incorporate emerging scientific tools and holistic approaches like One Health.
• Mandating science-based mixture assessments, harmonizing global standards, and implementing equity-driven policies are crucial for effective chemical safety.