Size-dependent toxicological effects of microplastics: A review

Industrialization has accelerated plastic production and emissions, resulting in pervasive environmental plastic pollution. Plastic debris can fragment into microplastics (<5 mm) and nanoplastics, collectively referred to as microplastics and nanoplastics (MNPs). Beyond their ubiquity in ecosystems, MNPs have also been detected in human-relevant matrices (e.g., placenta and breast milk), intensifying concerns about potential organ-specific health risks. Although particle size is increasingly recognized as a critical determinant of MNP toxicity, a cross-system synthesis of size-dependent effects and their implications for risk assessment remains incomplete. This review integrates current evidence on size-associated toxicological outcomes across major organ systems, including the digestive, reproductive, urinary, cardiovascular, respiratory, and nervous systems. Across many experimental settings, a broadly consistent pattern emerges in which smaller MNPs, particularly sub-10 μm particles and nanoscale plastics, more often elicit stronger adverse responses than larger particles. This tendency is generally consistent with size-related internal fate and tissue delivery that enhance barrier crossing and cellular interactions, thereby promoting oxidative stress and immune or inflammatory activation and ultimately contributing to organ-level impairment and functional disruption. Future studies should adopt harmonized size classification and reporting, appropriate exposure metrics, environmentally relevant test materials, and long-term or low-dose designs, complemented by human-relevant biomonitoring, to strengthen size-resolved risk assessment while prioritizing monitoring and mitigation of the difficult-to-capture sub-10 μm fraction.