Synergistic neurotoxicity of polystyrene nanoparticles and MEHP in zebrafish (Danio rerio)

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.