A critical review of nanoplastic bioaccumulation data and a unified toxicokinetic model: from teleosts to human brain

Nanoplastics (NP) are now detected in human blood and organs at concentrations reaching hundreds to thousands of parts per million, yet no quantitative framework has linked short-term laboratory uptake kinetics to long-term, organ-specific bioaccumulation in humans. Here we develop a minimal, mechanistically grounded toxicokinetic model that represents organisms as a sequential two-compartment system comprising a systemic gate-blood compartment governing entry and circulation, and organ-level tissue compartments controlling retention. Reanalysis of six independent uptake and depuration datasets in teleost fish (spanning four species, multiple organs, particle sizes from 20 to 500~nm, and exposure concentrations across four orders of magnitude) reveals a striking data collapse when expressed in normalized variables. This collapse shows that uptake dynamics are universally governed by a single dimensionless parameter, the systemic excretion capacity, which is generically small under experimental conditions, implying prolonged systemic residence of NP. Exploiting the scale-free structure of the model, we extrapolate these kinetics to humans and demonstrate that direct exposure from air and water cannot account for reported organ burdens, even under conservative assumptions of negligible clearance. Instead, mass-balance constraints identify dietary intake as the dominant pathway for systemic loading. At steady state, human organ concentrations follow a robust cubic scaling with tissue lipid fraction, yielding blood-to-brain enrichment factors of order $10^{3}$--$10^{4}$. This lipid-mediated enrichment, combined with inefficient systemic depuration, explains why the brain emerges as a dominant sink for environmental nanoplastics. Our results establish a unified, predictive toxicokinetic framework that quantitatively bridges short-term animal experiments and chronic human bioaccumulation.