Microplastics, the Trojan Horse Paradigm: Barriers to Traditional Toxicological Risk Assessment and Opportunities for NAMs.

Microplastic (MP) pollution poses an emerging and complex challenge to human and environmental health, yet gaps in exposure, toxicokinetics, and biological effects have limited traditional risk assessment. Evidence suggests MPs may contribute to metabolic dysfunction, neurotoxicity, immune dysregulation, and tissue damage, while in aquatic organisms they induce behavioural changes and oxidative stress. MPs can also act as “Trojan horses,” adsorbing and transporting heavy metals, pathogens, and persistent organic pollutants, further complicating exposure assessment. Despite these complexities, advances in research via NAMs offer opportunities to improve risk evaluation. Integrating physicochemical properties, co-contaminant interactions, and exposure dynamics into standardised, mechanistically informed methodologies can enable more accurate hazard identification and risk characterisation. By addressing these challenges proactively, scientists and regulators can transform uncertainty into actionable knowledge, guiding interventions to protect human health. Developing robust, adaptable frameworks for MP risk assessment positions the community to mitigate potential health impacts while informing policy and public health strategies.