ABSTRACT Di (2-ethylhexyl) phthalate (DEHP) is a high production volume chemical included on the first candidate list of “substances of very high concern” brought out by the European Chemicals Agency. Despite the available information, the basal cytotoxicity of this compound in mammalian cells is poorly understood. In this work, Vero cells derived from the kidney of green monkey were used to determine the cytotoxic effects of DEHP, using four biochemical endpoints: neutral red uptake, tetrazolium (MTT) reduction, LDH activity and cell protein content. Membrane-based assays were the most sensitive for detecting cytotoxicity in our experimental system and revealed that DEHP targets lysosomal membranes. An interesting finding of this study relate to moderate permeabilization of lysosomes during DEHP-mediated cytotoxicity in Vero cells, which did not trigger cell death and was completely reversible after drug withdrawal. Our results not only provide useful information on the primary subcellular targets and mechanisms underlying the toxicity of DEHP in mammalian cells, but also support the importance of considering multi-parametric methods to define the toxicological profile of chemical compounds.
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