Reproductive, endocrine, cytotoxic and genotoxic effects of acephate, carbendazim and mancozeb, isolated or in mixture: study of juvenile toxicity in rats

Abstract

Agrochemicals are the most widely used synthetic chemicals in the world. They are used to minimize pests that interfere with production of most agricultural crops. Since 2009, Brazil is the country that uses the largest quantities of agrochemicals in the world. Residues from these products contaminate food, soil and water, leading the entire world population to environmental exposure. Nowadays, this exposure occurs to complex mixtures of agrochemicals, which may establish synergistic or additive effects to one another, potentializing health damage. Some studies have been investigating injuries caused by mixtures of agrochemicals in experimental models, however the vast majority uses adult animals. In this context, the importance of juvenile / pre-pubertal toxicity studies has been highlighted in recent literature because it is a period of great sensitivity during postnatal development. Considering the scarcity of studies with chemical mixtures in juvenile toxicity models and the importance of these agrochemicals to brazilian scenery, this research project aims to investigate whether pre-pubertal exposure to low doses of Carbendazim, Acephate and Mancozeb, isolated or in combination, causes immediate impairment on reproductive and endocrine parameters and on DNA damage of juvenile Wistar male rats. These agrochemicals were chosen because National Agency of Sanitary Surveillance (ANVISA) published a report showing that they were present in the greatest quantities in Brazilian diet, often exceeding the Maximum Residue Limit (MRL) allowed by law. Rats will be exposed to the agrochemicals alone or in mixture, orally by gavage, from postnatal day 23 to 53, when they will be euthanized and evaluated for: (i) histomorphometric parameters of testis and epididymis and activity of antioxidant enzymes in these tissues; (ii) serum levels of sexual hormones and expression of endocrine receptors in testes and epididymis; (iii) Histopathology of liver and kidneys; (iv) DNA damage on blood cells and bone marrow (COMETA and micronucleus assays) . The initial hypothesis considers the occurrence of a synergic or additive effect among the three agrochemicals studied, potentiating the action of each individual chemical, interfering in the endocrine and oxy-redox homeostasis of the organism during this critical period of postnatal development of male reproductive system. Sexually immature male rats will be used as a experimental model, since they are more susceptible than adult animals, little studied, and mimic the condition of children exposed to agrochemicals in food. It is important to emphasize that general population is exposed to these chemicals agents through contaminated food, water and soil. (AU)