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

M.J Radha,P Mahaboob Basha

doi:10.1016/j.toxrep.2020.06.008

Abstract

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.

Highlights

Phthalate esters (PE) are synthetic organic molecules extensively used as plasticizers in consumer products and has become indispensable in the human routine lifestyle
Phthalate esters are classified into high molecular weight (MW) phthalate esters with 7–13 carbon atoms [Diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), di-2-propylheptyl phthalate (DPHP), diisoundecyl phthalate (DIUP) and diisotridecyl phthalate (DTDP)] and low molecular weight phthalate esters with 3–6 carbon atoms [di-n-butyl phthalate (DBP), diisobutyl phthalate (DIBP), butyl benzyl phthalate (BBP) and di-2-ethylhexyl phthalate (DEHP)] in their backbone
Their findings observed the significant increase in the level(s) of aspartate transaminase (AST) of hepatic tissue in Sprague Dawley (SD) rats upon exposure to phthalates such as DBP, diundecyl phthalate (DUP), DINP, monobutyl phthalate (MBuP/MBP), monobenzyl phthalate (MBeP)

Summary

Introduction

Phthalate esters (PE) are synthetic organic molecules extensively used as plasticizers in consumer products and has become indispensable in the human routine lifestyle. As the usage of plasticizers is on the rise and their nondegradability has led to their ubiquitous presence in the environment This has caused humans’ exposure of phthalates through air, water, food, and dermal contact leading to many health hazards [4,5,6,7,8]. Once phthalates gain entry into the body through air [4], water [5], and food [6], dermal contact [8], later transform into their corresponding metabolites rapidly and eliminate through urine and feces Their presence is detected in body fluids namely plasma, amniotic fluid, breast’s milk and urine of humans [10,11]. A decline in sperm count, incidence of cryptorchidism, and hypospadias have been reported [16,17]

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Discussion

Conclusion