The extensive usage of bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A
(BPA) creates a lot of opportunities for combined human exposure to these hazardous compounds in
everyday life and a variety of negative outcomes, including hepatotoxicity. In silico research and two
in vivo models were used to investigate the links between a mixture including DEHP, DBP and BPA and
liver injury. Bioinformatic analysis was performed by Comparative Toxicogenomics Database, ShinyGO,
ToppCluster, and Cytoscape. In vivo subacute study included five groups of rats (n = 6): (1) Control: corn
oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP
+ DBP + BPA. Zebrafish embryos were exposed to the investigated substances in multiple dosages, both
alone and in combination (binary and ternary mixtures). Liver damage was linked to 75 DEHP, DBP, and
BPA genes, the majority of which were associated with inflammation/oxidative stress, identified as the
most relevant molecular pathways. In rats, significant changes in redox status/bioelements’ level and
pathohistology were more pronounced or evident only in MIX group, suggesting probable additivity.
In a dose-dependent manner, BPA reduced the liver area (LA) index. LA values were decreased by DEHP
(2 μg/mL) and DBP (5 μg/mL), whereas LA index was raised by their higher concentrations. In binary
mixtures, DBP had a lethal effect at the two highest concentrations, whereas BPA directed hepatotoxicity
of the DEHP/DBP/BPA mixture
