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Deciphering size-dependent inter-organ translocation of nanoplastics in fish using metal-labeled proxies and physiologically based toxicokinetic modeling
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Researchers used metal-tagged nanoplastics to track how particles of two different sizes (50 nm and 200 nm) traveled through organs in zebrafish, finding that smaller particles spread more widely and recirculated longer, while gills were the primary entry route in water and the intestine was the main exit — providing the first detailed mathematical model of how nanoplastics move through a fish's body.
Nanoplastics (NPs) are extensively ingested by aquatic organisms, but quantitative inter-organ translocation kinetics remain poorly characterized, hindering their environmental risk assessment. We used metal-labeled NPs as proxies to trace bioaccumulation, biodistribution and depuration processes of two-sized NPs (200 nm L-NPs and 50 nm S-NPs) in zebrafish under environmentally relevant concentrations via waterborne (100 μg/L) and dietary (1000 μg/kg) exposure. Subsequently, we developed a physiologically based toxicokinetic model with seven compartments: blood, brain, gills, intestine, liver, gonad, and carcass. The model accurately described NPs toxicokinetics across compartments (overall R 2 ranging from 0.916 to 0.993). Organ exchange rates were quantified, revealing that NPs size determines inter-organ translocation capacity, with smaller NPs exhibiting stronger translocation capability. This model mathematically confirmed gills as the primary uptake route for aqueous NPs (>70 % mean contribution) and intestine as the major elimination route regardless of exposure pathway. Enterohepatic circulation was identified, with S-NPs showing enhanced recirculation capacity. Differential biological half-lives ( t 1/2 ) across organs caused tissue-specific residual patterns. Specifically, intestine dominated NPs distribution during exposure, whereas organs with longer t 1/2 (e.g., carcass) dominated residual NPs after depuration. This study provides a framework to quantify inter-organ translocation of NPs, elucidating the size-driven mechanisms governing tissue-specific burdens and environmental risks from different route exposures. • This is the first whole-body PBTK model for nanoplastics in fish. • Contributions of waterborne and dietary exposure to NPs bioaccumulation were quantified. • Smaller NPs demonstrated greater susceptibility to biotranslocation. • The gills as the primary uptake route for aqueous NPs and intestine as the major elimination route. • This model explains the tissue-specific residual patterns of NPs of different sizes.
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