Influence of Micro- and Nanoplastic Aging and Weathering on Human and Mammalian Health: A Systematic Review

Micro- and nanoplastics (MNPs) are widespread environmental contaminants, yet most toxicological studies use pristine materials that do not reflect environmentally induced transformations. This systematic review evaluated whether aged or weathered MNPs produce greater or altered biological responses than pristine particles and whether these effects are linked to changes in physicochemical properties. Following PRISMA guidelines and a PROSPERO-registered protocol, searches of PubMed, Web of Science, Scopus, and ProQuest identified 326 records published from 2015–2025. Seventeen studies met inclusion criteria, representing 19 data sets: 1 human, 3 animal, and 15 in vitro. Aging, primarily through UV and oxidation, consistently altered surface chemistry and often modified particle size, charge, colloidal behavior, corona formation, and contaminant interactions. These changes were frequently associated with increased oxidative stress, inflammation, molecular perturbation, and altered cellular behavior. However, evidence was dominated by acute in vitro studies using nominal mass-based dosing, with limited human and in vivo data. OHAT assessment indicated moderate confidence overall. Collectively, the evidence identifies aging and weathering as important determinants of MNP toxicity and highlights the need for standardized aging protocols, improved dosimetry, route-relevant exposures, and stronger integration of physicochemical and biological characterization.