Microplastics and Nanoplastics in Humans: A Critical ADME Appraisal and the Case for Quantitative Risk Assessment

Microplastics (MPs, 1 µm-5 mm) and nanoplastics (NPs, <1 µm) have now been detected in every environmental compartment and in human tissues, including blood, lung, placenta, liver, and brain. Detection alone, however, is not sufficient for health risk assessment. The critical question is not whether these particles are present in the body, but what happens to them once they are, a question that can only be answered with rigorous toxicokinetic data. This review critically evaluates the evidence on the absorption, distribution, metabolism, and excretion (ADME) of MPs and NPs in humans, applying an explicit evidence-level framework (Section 1.1) to weigh the quality of the underlying studies rather than simply summarising them. Gastrointestinal absorption is mechanistically plausible but quantitatively undefined: no human mass-balance study has yet measured an absorption fraction. Detection of plastic particles or polymer signatures in human blood and tissues demonstrates internal exposure, but does not by itself establish absorption fraction, tissue partitioning, retention, or systemic clearance. Polymer backbones resist enzymatic degradation, so classical metabolic biotransformation does not apply; surface oxidation and additive leaching are the primary biochemical interactions instead. Excretion pathways are constrained by particle size and remain poorly characterised, and systemic clearance kinetics are entirely unknown. These gaps are compounded by an analytical paradox: routine µFTIR and conventional Raman approaches have substantially poorer sensitivity in the submicrometre range, while emerging nano-Raman/TERS approaches can access smaller particles but remain insufficiently validated for complex human matrices, which limits detection of a particle fraction that may be particularly important for cellular uptake and barrier interactions. No PBTK model for MPs/NPs has yet been validated against human toxicokinetic or biomonitoring data. Turning environmental detection data into credible risk assessment will require standardised biomonitoring protocols, isotopically labelled tracer studies in humans, and a validated PBTK model. Until these foundations are in place, neither reassurance nor alarm about human health risk is scientifically justified.