Exploring the potential and challenges of developing physiologically-based toxicokinetic models to support human...

Microplastics (MPs) and nanoplastics (NPs) pollution has emerged as a significant and widespread environmental issue. Humans are inevitably exposed to MPs and NPs via ingestion, inhalation, and dermal contacts from various sources. However, mechanistic knowledge of their distribution, interaction, and potency in the body is still lacking. To address this knowledge gap, we have undertaken the task of elucidating the toxicokinetic (TK) behaviors of MPs and NPs, aiming to provide mechanistic information for constructing a conceptual physiologically based toxicokinetic (PBTK) model to support in silico modeling approaches. Our effort involved a thorough examination of the existing literature and data collation on the presence of MPs in the human body and in vitro/ex vivo/in vivo biodistribution across various cells and tissues. By comprehending the absorption, distribution, metabolism, and excretion mechanisms of MPs and NPs in relation to their physicochemical attributes, we established a foundational understanding of the link between external exposure and internal tissue dosimetry. We observed that particle size and surface chemistry have been thoroughly explored in previous experimental studies. However, certain attributes, such as polymer type, shape, and biofilm/biocorona, warrant attention and further examination. We discussed the fundamental disparities in TK properties of MPs/NPs from those of engineered nanoparticles. We proposed a preliminary PBTK framework with several possible modeling approaches and discussed existing challenges for further investigation. Overall, this article provides a comprehensive compilation of existing TK data of MPs/NPs, a critical overview of TK processes and mechanisms, and proposes potential PBTK modeling approaches, particularly regarding their applicability to the human system, and outlines future perspectives for developing PBTK models and their integration into human health risk assessment of MPs and NPs.