Nano- and microplastic PBK modeling in the context of human exposure and risk assessment

Insufficient data on nano- and microplastics (NMP) hinder robust evaluation of their potential health risks. Methodological disparities and the absence of established toxicity thresholds impede comparability and practical application of research findings. The diverse attributes of NMP, such as variations in sizes, shapes, and compositions, complicate human health risk assessment. Although probability density functions (PDFs) show promise in capturing this diversity, their integration into risk assessment frameworks is limited. Physiologically based kinetic (PBK) models offer a potential solution to bridge external exposure and internal dosimetry for risk evaluation. However, the heterogeneity of NMP poses challenges for accurate biodistribution modeling. A literature review encompassed both experimental and modeling studies was conducted to examine biodistribution studies of monodisperse micro- and nanoparticles. The literature search in PubMed and Scopus databases yielded 39 studies that met the inclusion criteria. Evaluation criteria were adapted from previous Quality Assurance and Quality Control (QA-QC) studies, best practice guidelines from WHO (2010), OECD guidance (2021), and additional criteria introduced to address the context of NMP risk assessment. Subsequently, a conceptual framework for a comprehensive NMP-PBK model was developed, addressing the multidimensionality of NMP particles. Model parameters for an NMP-PBK model are presented. The QA-QC evaluations revealed that most experimental studies receive relatively good scores (>0) for particle characterizations and environmental settings but lacked in the application for biodistribution model criteria. Meanwhile, the evaluation of modeling studies revealed that information regarding the model type and allometric scaling requires improvement. Three potential applications of PDFs in PBK modeling of NMP are identified: capturing the multidimensionality of the NMP continuum, quantifying the probabilistic definition of external exposure, and calculating the bio-accessibility fraction of NMP in the human body. A framework for an NMP-PBK model is proposed, integrating PDFs for enhanced risk assessment of the impact of NMP on human health.