The distribution of nano- and microplastics in the human body: a hybrid perfusion-diffusion based PBK model

A key bottleneck in human health risk assessment of nano- and microplastics (NMPs) is the limited applicability of physiologically based kinetic (PBK) models that simulate particle distributions within the body based on external exposure. Many existing models of NMP are mass-based, even though risk assessment requires particle numbers and size distributions, and they enforce a binary choice between perfusion- and diffusion-limited transport. Here, we develop a probabilistic PBK model for polydisperse NMPs that smoothly shifts from perfusion to diffusion as particle size increases and predicts particle numbers and size distributions across organs. We calibrate the model within realistic parameter bounds using mouse kinetic data, scale it to human physiology, and apply it to realistic polydisperse exposure scenarios for both inhalation and ingestion. Model evaluation showed strong agreement with observed tissue concentrations for inhalation and ingestion, with most predictions accurate within a factor of five. Simulations revealed route-specific kinetics: inhalation burdens were driven by respiratory retention and mucociliary transfer to the gastrointestinal tract, with fecal elimination as the dominant pathway. In contrast, ingestion yielded near-complete elimination, low systemic burdens, and fecal dominance. For inhalation, size distributions were mainly dominated by 50-100 nm particles, whereas ingestion showed smaller particles in systemic organs and larger fractions retained in the gastrointestinal tract. Despite the scarcity of human data, our probabilistic whole-body PBK model integrates experimental biodistribution data with environmentally realistic, polydisperse NMP exposures to simulate internal tissue concentrations across the full NMP size continuum and establishes a mechanistic foundation for NMP risk assessment.