Polymer identity determines nanoplastic toxicity: A toxicokinetic–toxicodynamic analysis

Nanoplastics (NPs) are widespread in aquatic environments, yet current toxicological studies overwhelmingly focus on polystyrene (PS), overlooking the diverse polymers present in natural systems. To address this gap, the present study compared four common NPs derived from different polymers: polycarbonate (PC), polymethyl methacrylate (PMMA), PS, and polyvinyl chloride (PVC), using the freshwater protozoan Tetrahymena thermophila as a model. Aggregation-induced emission (AIE) labeling enabled precise quantification of intracellular NP burdens, and we applied a toxicokinetic-toxicodynamic (TK-TD) framework incorporating a damage assessment model (DAM) to mechanistically link internal NP doses to Ca dysregulation. We found that PMMA and PS NPs accumulated most readily but induced only moderate oxidative stress, Ca imbalance, and membrane damage. In contrast, PVC NPs produced the strongest perturbations and exhibited the highest TD damage accumulation rate, demonstrating that polymer chemistry rather than internal dose alone governs toxic potential. Notably, PS, despite being the dominant model plastic in NP toxicology, was the least potent in our assays, whereas globally prevalent polymers such as PVC showed substantially stronger TD effects. These findings highlight the need to broaden NP risk assessment beyond PS-centric approaches and establish a predictive, mechanism-based framework for evaluating polymer-specific NP toxicity in aquatic ecosystems.