Hepatotoxic evaluation of Di- n-butyl phthalate in Wistar rats upon sub-chronic exposure: A multigenerational assessment

The extensive use of di--n-butyl phthalate (DBP) as a plasticizer in medical devices, personal care products, and industries, which is a major threat to humankind as it leaches out easily from the plastic matrix into the environment. Health risks posed to adults and children from the broad usage of DBP in cosmetics and infant toys observed predominantly due to repeated and prolonged exposure. Hence, this study was undertaken to evaluate the potential effect of DBP in the hepatic tissue of rats up to three generations. Wistar rats were induced at a dose of 500 mg DBP /kg body weight dissolved in olive oil by oral gavage throughout gestation (GD 6-21), lactation and post-weaning and reared by crossing intoxicated rats up to three generations. Results of the present study showed a significant increase in the relative weight of liver, while decreased levels of antioxidant enzymes viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) was evident in DBP treated rats at P < 0.05. Besides hepatic marker enzymes viz., alanine transaminase (ALT) and aspartate transaminase (AST) were elevated significantly in experimental rats compared to those of the control group. Furthermore, histological studies revealed congested central veins and dilated sinusoids in F₁ progeny while mild to severe focal inflammatory infiltrations were evident in F₂ & F₃ rats. Negative correlation observed between the levels of antioxidant enzymes and transaminase activity. In brief, DBP exposure elicits oxidative stress and alters the transaminase activity levels causing damage in hepatic tissue. F₃ progeny found to high vulnerability to the exposure of DBP than F₂ & F₁ rats.

Keywords: Di-n-butyl phthalate; Hepatotoxicity; Multigenerational assessment; Oxidative stress.