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Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that gives flexibility to various polyvinyl chloride products. It is a pollutant easily released into the environment and can cause many adverse effects to living organisms including hepatotoxicity. The thioredoxin system is a determining factor in the redox balance maintaining in the liver, which is a vulnerable tissue of reactive oxygen species overproduction because of its high energy needs. In order to determine if the thioredoxin system is a target in the development of DEHP hepatotoxicity, Balb/c mice were administered with DEHP intraperitoneally daily for 30 days. Results demonstrated that after DEHP exposure, biochemical profile changes were observed. This phthalate causes oxidative damage through the induction of lipid peroxydation as well as the increase of superoxide dismutase and catalase activities. As new evidence provided in this study, we demonstrated that the DEHP affected the thioredoxin system by altering the expression and the activity of thioredoxin (Trx) and thioredoxin Reductase (TrxR1). The two enzyme activities of the oxidative phase of the pentose phosphate pathway:Glucose-6-phosphate dehydrogenase and 6-Phosphogluconate dehydrogenase were also affected by this phthalate. This leads to a decrease in the level of nicotinamide adenine dinucleotide phosphate used by the TrxR1 to maintain the regeneration of the reduced Trx. We also demonstrated that such effects can be responsible of DEHP-induced DNA damage. K E Y W O R D S di (2-ethylhexyl) phthalate, DNA damage, oxidative stress, pentose phosphate pathway, thioredoxin system 1 | INTRODUCTION Di (2-ethylhexyl) phthalate (DEHP) is an organic compound abundantly used as a plasticizer to soften and increase the flexibility ofplastic. It has aroused public concern since the large mass of DEHPbased product frequently used like food packaging, cosmetics, perfumes, and medical devices. 1 Due to its low covalent binding to plastic polymers, DEHP can migrate from plastic matrix to foods, beverages, and even in a direct way in body fluids. 2 Therefore, exposure to this phthalate appears to be inevitable and humans may be exposed to it through digestive system and skin absorption or via inhalation. Nakamiya et al 3 reported that human body introduces around 25 mg of DEHP every day only from food. It was found that DEHP concentrations are approximately 25 mg/kg in cheese, 158 mg/kg in oily