UV-aging process of titanium dioxide nanoparticles aggravates enterohepatic toxicity of bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate to zebrafish

The physicochemical characteristics of titanium dioxide nanoparticles (n-TiO2) may change during the aging process once discharged into aquatic environment. However, how the aging process affects their interactions with co-existing pollutants, as well as the joint toxicity has not been explored. This study investigated how UV-aging impacts n-TiO2 in aquatic environments and their interactions with bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), focusing on their joint toxicity in adult female zebrafish. UV-aging process significantly increased the specific area and hydrophobicity of n-TiO2, promoting the adsorption of TBPH. In vivo experiments revealed that aged n-TiO2 enhanced the bioaccumulation of TBPH in the liver and intestine, worsening hepatic steatosis and intestinal barrier damage. A combined analysis of hepatic lipidomic profiling and intestinal microbiota 16S rRNA sequencing revealed that co-exposure of aged n-TiO2 and TBPH altered gut microbial composition and abundances, facilitating the circulation of lipopolysaccharides (LPS) through the gut-liver axis. Subsequentially, the elevated LPS level in the liver activated the sphingolipid metabolic pathway, resulting in severer lipid metabolism disorders and hepatotoxicity. This study found that UV-aging increases the hydrophobicity and surface area of n-TiO2, enhancing their interaction with the TBPH, which leads to greater bioaccumulation and hepatoxicity through mechanisms involving changes in gut microbiomes and sphingolipid metabolism. © 2024 Elsevier B.V.