A Mixture of Endocrine Disruptors and the Pesticide Roundup (R) Induce Oxidative Stress in Rabbit Liver When Administered under the Long-Term Low-Dose Regimen: Reinforcing the Notion of Real-Life Risk Simulation

Humans are exposed to xenobiotic mixtures daily through the long-term, low-dose regimen. Investigations designed to simulate this exposure profile approach the real-life risk simulation (RLRS) idea of modern toxicology. The purpose of the present study was to investigate the effects of 12-month exposure of New Zealand rabbits to a xenobiotic mixture comprising seven endocrine disruptors (EDs), which are chemical substances raising great concerns for human health, as well as the herbicide glyphosate, and its commercial formulation Roundup (R), on blood and tissues redox status. It is reported herein that at the systemic level, the administration of the EDs mixture induced perturbations of blood redox homeostasis at 3 months, whereas at 6 and 12 months, it activated redox adaptations. Contrariwise, exposure to glyphosate and Roundup (R), individually, caused mainly disturbances of blood redox equilibrium. At the tissue level, particularly in the liver, the administration of both the EDs mixture and Roundup (R) induced oxidative stress, whereas glyphosate did not affect it. The RLRS notion appears to be confirmed through these findings. Indeed, the administration of the EDs mixture and Roundup (R), under the long-term, low-dose regimen, elicited detrimental effects on the redox status of the liver, a crucial tissue with a valuable biological role in the detoxification of organisms from xenobiotics.