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Numeric uptake drives nanoplastic toxicity: Size-effects uncovered by toxicokinetic-toxicodynamic (TKTD) modeling
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This study used mathematical models to predict how different sizes of nanoplastics accumulate in and harm tiny water organisms (Daphnia magna). The smallest nanoplastics (30 nanometers) were the most toxic because they spread throughout the body, while larger ones mostly stayed in the gut. This size-dependent toxicity pattern is important because it suggests that the tiniest plastic particles, which are hardest to detect, may pose the greatest health risks.
Predicting nanoplastic bioaccumulation and toxicity using process-based models is challenging due to the difficulties in tracing them at low concentrations. This study investigates the size-dependent effects of nanoplastic exposure on Daphnia magna using a toxicokinetic-toxicodynamic (TKTD) model. Palladium-doped fluorescent nanoplastics in three sizes (30-nm, 66-nm, 170-nm) were tested at two numeric exposure concentrations. The TK model reproduced nanoplastic uptake and elimination, indicating a uniform elimination rate constant (0.035 h) across sizes, while uptake rate constants (k) varied by size and concentration. Fluorescence analysis revealed larger nanoplastics (66-nm, 170-nm) accumulated primarily in the intestine, while smaller nanoplastics (30-nm) were more widely distributed. Re-modeling uptake specifically for the intestine showed consistent trends in the uptake rate constants, with larger nanoplastics exhibiting higher ingestion efficiency. Toxicity effects mirrored the order of whole-organism nanoplastic uptake: 30-nm nanoplastics were most toxic, 170-nm nanoplastics showed slight toxicity, and 66-nm nanoplastics were non-toxic. The TD model suggested similar hazard potentials across sizes, with observed toxicity differences likely driven by whole-organism particle uptake. The TKTD model predicted no-effect concentrations at 1.8 × 10 and 6.0 × 10 particles L for 30-nm and 170-nm nanoplastics, respectively, corresponding to mass concentrations of 2.54 and 1540 mg L. These values are significantly higher than reported environmental levels, indicating a low current toxicity risk to D. magna. Overall, this study enhances understanding of how size-dependent uptake behaviors influence nanoplastic toxicity, stressing the need for more accurate assessment of hazards linked to low-size nanoplastics and supporting more informed decision-making in nanoplastic pollution management.
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