Risk Assessment of Chemical Mixtures in Foods: A Comprehensive Methodological and Regulatory Review

Area of Science:

• Food safety and toxicology
• Environmental health risk assessment
• Chemical mixture analysis

Background:

• Mixture risk assessment for food xenobiotics has evolved significantly over 15 years.
• Early methods like the Hazard Index (HI) have been succeeded by sophisticated, component-based, and probabilistic frameworks.
• These advancements are integrated into major food-safety institutions globally.

Purpose of the Study:

• To review methodological and regulatory progress in cumulative risk assessment for dietary mixtures of pesticides, contaminants, and other xenobiotics.
• To focus on food-relevant exposure scenarios and toxicological paradigms.
• To outline a coherent, tiered, and uncertainty-aware framework for assessing real-world dietary mixtures.

Main Methods:

• Synthesizing advances in toxicology, focusing on concentration/dose addition as the default model for similarly acting chemicals.
• Reviewing quantitative metrics like Relative Potency Factors (RPF), Toxic Equivalents (TEQ), Maximum Cumulative Ratio (MCR), and combined Margin of Exposure (MOET).
• Examining regulatory frameworks from EFSA, U.S. EPA, and FAO/WHO, and the role of Total Diet Studies and human biomonitoring.

Main Results:

• Dose addition is supported by evidence for environmental mixtures at low effect levels.
• Quantitative metrics operationalize component-based mixture assessment, aiding in risk characterization.
• Regulatory bodies are converging on tiered schemes, chemical grouping, and dose addition, with variations in implementation.

Conclusions:

• A coherent, tiered, and uncertainty-aware framework for assessing dietary xenobiotic mixtures is presented.
• Implementation relies on robust exposure data from Total Diet Studies and human biomonitoring.
• Future priorities include data-driven grouping, pharmacokinetic modeling, and refined mixture-sensitive indicators for public health.