Microplastics and nanoplastics (MNPs) are ubiquitous in our environment (FPF reported), leading to chronic exposure in humans (FPF reported and here). Despite their prevalence and potential health risks, the fate of these particles in the human body remains poorly understood.

Physiologically-based toxicokinetic (PBTK) models are quantitative computational tools used to predict the absorption, distribution, metabolism, and excretion of substances within the body. For engineered nanoparticles in medical settings, PBTK models help scientists understand how these particles interact with biological systems, ensuring safety and efficacy.

A recent study by Chi-Yun Chen and Zhoumeng Lin, from the University of Florida in the US collected data from in-vitro, ex-vivo, and in-vivo studies to assess the absorption, distribution, metabolism, and excretion of MNPs. Published in Environment International in April 2024, their research aims to fill this MNP fate gap by reviewing the information necessary to construct a preliminary PBTK model for MNPs.

MNPs enter the body primarily via ingestion and inhalation; absorption through the skin is mostly insignificant except for MNPs intentionally used in personal care products. Both membrane-crossing and endocytosis, the uptake of matter into the cell by forming a membrane-surrounded vesicle, are relevant pathways for MNPs to get into cells. Membrane-crossing is mainly possible for smaller and negatively charged MNPs.

Distribution studies in animals show that MNPs accumulate in the spleen and the liver, with small particles being the most mobile. Human tissue samples also demonstrate that these small particles (< 10 μm) can reach the brain, placenta, and testis (FPF reported, here and here).

During metabolism, MNPs are not easily broken down in mammals, instead a “biocorona” of proteins on their surface is formed. These surface changes alter the particle’s binding affinity to structures in the body, e.g. increasing sorption to blood serum protein. The unmetabolized particles are primarily excreted via feces instead of urine. Smaller particles linger longer in the body, showing experimental half-lives of up to 37 hours in animal models.

The study highlights significant differences between MNPs and engineered nanoparticles used in medical applications. These differences “pose significant challenges when attempting to apply PBTK models originally designed for engineered nanoparticles to [MNPs]”.  Unlike specially engineered particles, MNPs have diverse shapes, sizes, polymer types, and compositions, with the added complication of previous weathering.

Most studies on the toxicokinetic behavior of MNPs investigated standardized polystyrene beads (FPF reported, and here) and often used in-vitro or mice models, limiting the generalizability of the results.  To create more accurate PBTK models the authors recommend that future research consider a broader range of factors beyond particle size and surface charge, including polymer type, shape, surface biofilms, and biocorona. They also emphasize the importance of studying inhalation as an exposure route, the effects of repeated doses versus single doses, and the translation of findings from model systems to the human body.

A complementary review by Myriam Borgatta and Florian Breider from the University of Lausanne and EPFL in Switzerland also emphasizes the need for better inhalation data. They found that particles smaller than 1 μm can reach deep lung regions, causing various toxic effects such as alveolar injury and breathlessness. MNP-associated chemicals may contribute to lung toxicity and potentially enter the bloodstream, leading to systemic exposure. The review points to the limited number of studies investigating the inhalation of MNPs, and they call for “a multidisciplinary approach [that] will enable a comprehensive understanding of the toxicological effects of [MNPs] via inhalation”.

 

References

Chi-Yun Chen & Zhoumeng Lin (2024). ‘Exploring the potential and challenges of developing physiologically-based toxicokinetic models to support human health risk assessment of microplastic and nanoplastic particles’. Environment International. DOI: 10.1016/j.envint.2024.108617

Myriam Borgatta & Florian Breider (2024). ‘Inhalation of Microplastics-A Toxicological Complexity’. Toxics. DOI: 10.3390/toxics12050358

 

Other recent research

Braun A. & Seitz Harald (2024) ‘Uptake and Cellular Effects of Polymethylmethacrylate on Human Cell Lines’. Microplastics. DOI: https://doi.org/10.3390/microplastics3020012

Jeong J., et al. (2024) ‘Integrating aggregate exposure pathway and adverse outcome pathway for micro/nanoplastics: A review on exposure, toxicokinetics, and toxicity studies.’ Ecotoxicology and Environmental Safety. DOI: 10.1016/j.ecoenv.2024.116022