Toxicokinetic-toxicodynamic modeling reveals the ecological risks of differently-sized polystyrene nanoplastics

The nanoplastics (NPs) in aquatic ecosystems poses significant ecological risks, yet their environmental safety thresholds remain poorly defined. Here, we employed a toxicokinetic-toxicodynamic (TK-TD) modeling framework to investigate the bioaccumulation and toxicity of 30- (PS₃₀), 60- (PS₆₀), 80- (PS₈₀), 120- (PS₁₂₀), and 200-nm (PS₂₀₀) polystyrene (PS) NPs in the zooplankton Daphnia magna. The PS NPs were labeled with aggregation-induced-emission fluorogens when necessary, thereby enabling precise tracking of their bioaccumulation. Fluorescence imaging revealed that larger PS NPs primarily accumulated in the gut, whereas smaller particles preferentially localized on thoracic appendages. Both uptake and elimination rates increased with particle size, except for PS₁₂₀, which exhibited the lowest elimination rate, likely due to entrapment in intestines. Toxicity assessments indicated that smaller PS NPs exhibited higher toxicity, which disrupted nutrient digestion and induced oxidative stress, as evidenced by transcriptomic analyses. Using the TK-TD model, we predicted the 48-h LC50 values for PS₃₀, PS₆₀, PS₁₂₀, PS₈₀, and PS₂₀₀ to be 1.2, 3.0, 13.5, 14.4, and 196.7 mg L⁻¹, respectively. The corresponding no-effect concentrations were 0.15, 1.05, 6.9, 8.2, and 92.7 mg L⁻¹. Overall, our study establishes a TK-TD framework to predict the toxicity of PS NPs under controlled conditions, providing foundational data for future environmental risk assessments.