Co-exposure of TMPs and antibiotics in zebrafish: The influence of additives on the risk of hepatotoxicity

Co-exposure of tire microplastics (TMPs) and antibiotics has been confirmed to pose toxic risks to aquatic organisms. However, the contributions of TMP additives to these risks and the underlying mechanisms remain underreported. In this study, factor analysis and molecular docking and molecular dynamics simulations were employed to investigate the differential additive-related hepatotoxicity risks associated with TMP-antibiotic exposure in zebrafish. The differential hepatotoxicity risks of five types of TMPs and six antibiotics were simulated in the presence of additives. Zebrafish exposed to different TMPs showed significant differences in hepatotoxicity risks, with styrene-butadiene rubber (SBR) exhibiting the most pronounced toxic effects. The additive contribution analysis revealed that in the presence of SBR additives, TMPs-antibiotics posed higher toxicity risks to the cytochrome P 17A2 (CYP17A2) isoenzymes CYP2K19, CYP1A, CYP3A65, and CYP2K22 in zebrafish, showing synergistic effects primarily driven by plasticizers. Furthermore, the hepatotoxicity risks of TMPs-antibiotics in zebrafish in the presence of additives were significantly mitigated by the selection of alternative plasticizers. The micromechanisms by which additives affected the TMP-antibiotic hepatotoxicity risks in zebrafish were elucidated through mechanistic analysis. This study aimed to characterize the additive-influenced hepatotoxicity risks of TMPs-antibiotics, providing micro-level insights and theoretical support for ecological risk assessments in aquatic environments.