A physiologically based toxicokinetic model for microplastics and nanoplastics in mice after oral exposure and its implications for human dietary exposure assessment

Evidence of microplastics (MPs) and nanoplastics (NPs) in foods and daily-use products, along with their frequent detection in the human body, has raised concerns regarding their potential impact on human health through dietary ingestion. However, there is a lack of quantitative tools to simulate their bioaccumulation and tissue distribution following environmental exposure. To address this gap, we developed the first physiologically based toxicokinetic (PBTK) model for predicting the biodistribution of MPs and NPs in mice following oral exposure under various exposure scenarios. This novel model incorporated key kinetic mass transport processes, such as membrane permeability, albumin binding, and cellular uptake. We identified that the absorption rate in the gastrointestinal tract and fecal excretion rate constant had significant impacts on organ dosimetry. Our regression analysis indicated that the size-dependent dissociation constant and urine clearance rate constant sharply increased by a factor of 3 as NPs particle size increased to 1 µm. Finally, we developed a graphical user interface to enable interactive visualization and analysis for future applications, supporting human dietary exposure and risk assessment using available food consumption data and MPs/NPs residue data. The simulation results offer a mechanistic perspective, enhancing understanding of the internal organ dosimetry burden and health impacts from dietary exposure to MPs and NPs.