Liu_2025_Environ.Pollut_382_126765

The surge in global plastic usage has exacerbated the pollution of nanoplastics and plasticizers in aquatic ecosystems, causing widespread concern about population health issues. We used a zebrafish model to investigate the combined toxicity of polystyrene nanoparticles (PS-NPs) and plasticizer metabolite mono-(2-ethylhexyl) phthalate (MEHP), revealing the synergistic neurotoxic effects and potential mechanisms of compound exposure. Co-exposure amplifies the bioaccumulation of PS-NPs (p < 0.05), causing innate immune damage (p < 0.0001), severe oxidative stress (p < 0.0001), and embryonic apoptosis (p < 0.05), while inducing larval neuromotor dysfunction and changes in neural markers. Further exploration revealed that oxidative stress-induced lipid peroxidation disrupts glycerophospholipid metabolism and cholinergic synthesis, which can be an important mechanism for neurotoxicity caused by the co-exposure of PS-NPs and MEHP. This hypothesis is supported by dysregulation of acetylcholinesterase (ache), docking protein 7 (dok7), and heparan sulfate proteoglycan 2 (hspg2) genes linked to neurotransmission. In summary, this study reveals new synergistic toxicity mechanisms between nanoplastics and plasticizers, advancing the risk assessment framework for complex environmental pollutant interactions.