Abstract

Micro- and nanoplastics (MNPs) - particles derived from the fragmentation of larger plastic debris or manufactured 
intentionally at microscopic scales - are now ubiquitous across terrestrial, freshwater, marine, and atmospheric 
environments. Their small size, high surface area, and capacity to carry additives and sorbed pollutants enable them 
to interact with biological systems in ways that larger plastic debris cannot. This review synthesizes current 
understanding of the biochemical mechanisms underlying MNP toxicity across biological kingdoms, emphasizing 
oxidative stress, membrane and protein interactions, immune activation and inflammation, genotoxicity, endocrine 
disruption, and microbiome perturbation. We discuss routes of exposure and internalization, particle 
physicochemistry that modulates bioactivity, cross-species comparability of effects (plants, invertebrates, 
vertebrates, and humans), and methodological challenges in detection and hazard assessment. Gaps are highlighted: 
standardization of particle characterization and dose metrics, elucidation of chronic low-dose effects and mixture 
interactions, and development of mechanistic biomarkers translatable between models and humans. The review 
concludes with priority research directions and implications for risk assessment and public health policy, arguing 
that addressing MNP toxicity requires coordinated advances in analytical methods, experimental design, and cross
disciplinary communication.