Synergistic toxicity of additive-functionalized microplastics in zebrafish: Linking intestinal release kinetics to...

Additive-bearing microplastics (MPs) represent an emerging class of aquatic contaminants, yet the bio-release behavior and toxicity mechanisms of their embedded additives remain poorly characterized. Here, using zebrafish and fluorescent MPs based on twisted intramolecular charge transfer (TICT) as model systems, we compared three additive-loaded TICT-MPs-incorporating antioxidant (AO), antistatic agent (ASA), and flame-retardant (FR)-to demonstrate that intestinal accumulation kinetics, additive release, and the resulting toxicological effects of MPs are strongly governed by their chemical properties and functionalization types. Results indicated that over 90% of TICT-MPs accumulated in the intestine, with positively charged ASA-TICT-MPs exhibiting the highest retention. Additive release kinetics further revealed that the intestinal environment markedly promoted additive leaching, with ASA-TICT-MPs showing the fastest release rate, whereas AO-TICT-MPs released additives minimally. Toxicologically, FR-TICT-MPs induced the most severe intestinal damage, amplifying oxidative stress through combined chemical toxicity and physical irritation-causing sharp increases in reactive oxygen species (ROS) and depletion of glutathione (GSH). ASA-TICT-MPs triggered moderate oxidative stress accompanied by compensatory GSH elevation, while AO-TICT-MPs exhibited negligible effects. Mechanistically, all toxic types of TICT-MPs disrupted intestinal redox homeostasis through the ROS-GSH pathway. Overall, this study elucidates how intestinal conditions accelerate additive release from MPs and systematically reveals pathway-specific toxicity initiated by different functionalized MPs, providing a theoretical basis for assessing the health risks of additive-containing MPs.