Micro- and Nanoplastics in the Human Exposome: Environmental Pathways, Kidney Toxicity, and Implications for Public Health Risk Assessment.

Plastic pollution has emerged as a global environmental and public health crisis, with micro- and nanoplastics (MNPs) representing a pervasive component of the human exposome. Generated through the continuous fragmentation of larger plastic materials, MNPs exhibit physicochemical properties that influence their environmental fate, biological interactions, and toxic potential. Human exposure occurs primarily through ingestion and inhalation, facilitating particle translocation across biological barriers and systemic distribution. Experimental studies have shown that MNP exposure can disrupt mitochondrial and lysosomal function, induce oxidative stress and DNA damage, and modulate inflammatory, apoptotic, and fibrotic pathways. Although evidence supports their multiorgan toxicity, the kidney has emerged as a critical target organ due to its role in filtration and excretion. Experimental studies, often conducted at concentrations exceeding estimated environmentally relevant exposure levels, have associated renal MNP exposure with oxidative injury, apoptosis, and fibrotic remodeling, while emerging mechanistic findings suggest potential links to pro-oncogenic cellular alterations; however, these effects have not been established in humans, and their clinical relevance remains uncertain. Furthermore, the detection of plastic particles in human blood, tissues, and urine underscores the translational relevance of MNP exposure while highlighting important gaps in exposure assessment, dose-response characterization, and mechanistic understanding. In this narrative review, we integrate current evidence regarding environmental exposure pathways, biodistribution, and molecular mechanisms of MNP-induced toxicity, emphasizing the need for integrated exposome-based approaches, omics technologies, advanced experimental models, and longitudinal studies to improve human health risk assessment and guide regulatory policies.