Assessment of acute and chronic toxicity of the heart and brain exposed to pesticides found in potable water in Brazil

Abstract

Brazil is the third country in the world in total tons of pesticides use per year. Pesticides are toxic substances or a mixture of substances that are naturally or chemically synthesized. They are widely used in agriculture to control plagues; however, since they are toxic to life, they are inevitably toxic to humans. Heavy use of pesticides has contaminated ecosystems. In Brazil, at least 27 pesticides are found in potable water, with a range of concentrations. Ministry of Health set concentration threshold levels for each pesticide, in theory not toxic, allowed to be found in potable water. However, in the literature, there is no systematic investigation of heart and nervous system toxicity of human tissue by these compounds at concentrations set by Ministry of Health. Also, there is no information if a mixture of these pesticides potentiates toxicity. Thus, to address these questions, we had the following aims: 1) evaluate in vitro single or mixture of pesticides in acute and chronic toxicity for cardiomyocytes and neurons derived from human-induced pluripotent stem cells, using the concentration approved by the Ministry of Health; 2) using mice determine in vivo if long-term low dose of single or a mixture of pesticides impact the functioning of the heart and central nervous system; 3) investigate in vivo how long-term low-dose pesticides impact the functioning of the heart and central nervous system in offspring of pregnant mice exposed to pesticides during pregnancy; 4) if SCN5A polymorphisms enhance the potency and toxicity of pesticides in vitro. At the end we will be able to determine the safety of potable water of Brazil in terms of pesticide contamination or if changes are needed in the guidelines of Ministry of Health. (AU)