Chronic exposure to diisopentyl phthalate impairs behavior, metabolism, and reproductive processes in adult female zebrafish (Danio rerio)

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The widespread use of diisopentyl phthalate (DiPP) in plastics and consumer products has raised concerns due to its potential endocrine-disrupting effects and detection in biological samples from humans, including pregnant women. However, the chronic multi-system toxicity of DiPP at environmentally relevant concentrations in adult vertebrates remains poorly characterized. To address this gap, adult female zebrafish (Danio rerio) were chronically exposed (30 days) to environmentally relevant DiPP concentrations (31.25, 62.5, and 125 μg/L), with a focus on reproduction, metabolism, and neurobehavior. The DiPP concentrations in the tank water were analytically confirmed by gas chromatography-mass spectrometry. The effects of chronic DiPP exposure on the molecular markers were evaluated only at the high exposure concentration (125 μg/L). The oxidative stress was reflected by dysregulated antioxidant genes (nfe2l2a, nfe212b, sod2, and cat; upregulation in the brain; downregulation in the liver). An increase in the proportion of mature follicles, dysregulation of estrogen signaling genes (downregulation of esr1, esr2a, and esr2b in the brain; upregulation of cyp19a1a in the ovary), and changes in ovarian morphology were also observed. Metabolic analyses revealed alterations in lipid and glucose homeostasis, alongside upregulation of hepatic apoptotic markers and detoxification pathway genes. DiPP also caused anxiety-like behavior and reduced social interaction without motor impairment. Collectively, these findings demonstrate that environmentally relevant DiPP concentrations cause multi-system toxicity affecting reproduction, metabolism, and neurobehavioral processes in female zebrafish. This suggests potential ecological risks of DiPP for aquatic populations and underscores the need for regulatory considerations in DiPP use as a plasticizer.