The combined neurotoxicity of DBP and nano-TiO2 in embryonic zebrafish (Danio rerio) revealed by oxidative activity, neuro-development genes expression and metabolomics changes

Dibutyl phthalate (DBP) is a commonly used plasticizer that is frequently detected in water samples due to its widespread use. Titanium dioxide nanoparticles (n-TiO 2 ) have been found to enhance the harmful effects of organic contaminants by increasing their bioavailability in aquatic environments. However, the combined toxic effects of DBP and n-TiO 2 on aquatic organisms remain unclear. This study aimed to investigate the neurotoxicity of DBP and n-TiO 2 synergistic exposure during the early life stage of zebrafish. The results of the study revealed that co-exposure of DBP and n-TiO 2 led to an increase in deformities and a significant reduction in the active duration of zebrafish larvae. Furthermore, the co-exposure of DBP and n-TiO 2 resulted in elevated levels of oxidative stress and altered gene expression related to neurodevelopment and apoptosis. Notably, n-TiO 2 exacerbated the oxidative damage and apoptosis induced by DBP alone exposure. Additionally, co-exposure of the 1.0 mg/L DBP and n-TiO 2 significantly affected the expression of genes associated with neurodevelopment. Moreover, disturbances in amino acid metabolism and interference with lipid metabolism were observed as a result of DBP and n-TiO 2 co-exposure. In general, n-TiO 2 aggravated the neurotoxicity of DBP in the early life stage of zebrafish by increasing oxidative stress, apoptosis, and disrupting amino acid synthesis and lipid metabolism. Therefore, it is essential to consider the potential risks caused by DBP and nanomaterials co-existence in the aquatic environment.