Hepatotoxic effects of chronic exposure to environmentally relevant concentrations of Di-(2-ethylhexyl) phthalate (DEHP) on crucian carp: Insights from multi-omics analyses

Di-(2-ethylhexyl) phthalate (DEHP) is an extensively used phthalate esters (PAEs) that raise growing ecotoxicological concerns due to detrimental effects on living organisms and ecosystems. This study performed hepatotoxic investigations on crucian carp under chronic low-dosage (CLD) exposure to DEHP at environmentally relevant concentrations (20–500 μg/L). The results demonstrated that the CLD exposure induced irreversible damage to the liver tissue. Multi-omics (transcriptomics and metabolomics) analyses revealed the predominant toxicological mechanisms underlying DEHP-induced hepatotoxicity by inhibiting energy production pathways and the up-regulation of the purine metabolism. Disruption of metabolic pathways led to excessive reactive oxygen species (ROS) production and subsequent oxidative stress. The adverse metabolic effects were exacerbated by an interplay between oxidative stress and endoplasmic reticulum stress. This study not only provides new mechanistic insights into the ecotoxicological effects of DEHP under chronic low-dosage exposure, but also suggests a potential strategy for further ecological risk assessment of PAEs.