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Validation of in vitro cell systems to assess the toxicity of socially relevant environmental pollutants

Abstract

Humans are exposed to a multitude of chemicals in their daily lives: pesticides, pharmaceuticals, industrial chemicals, among other substances, whether through production, consumption, presence in the environment or incorrect disposal. To ensure the protection of human health and the environment, it is essential that the toxicological potential of these compounds is properly selected. Experimental studies have the ability to predict the toxicity of emerging environmental contaminants, being useful for understanding the biological environments involved in health risk and also to support regulatory decisions by health and environmental agencies. Currently, the use of alternative toxicity methods from criteria to policy is an international assessment in response to the 3Rs in animal experimentation, which restricts the use of animals in research. Among the new alternative methodologies applied to toxicology are monolayer (2D), three-dimensional (3D) cell cultures and 3D Bioprinting, which can use different cell lines, such as human liver, urothelial and muscle cells. Also, these alternative methodologies can contribute to elucidate key mechanisms of toxicity of environmental contaminants and assist in the construction of conceptual frameworks ("Adverse Outcome Pathways", AOPs) that inform the mode of action (MoA) and the mechanisms of harmful action of those contaminants. This project, which puts us in line with the world trend of using alternative methods to assess the risk of chemical compounds, aims to evaluate the toxicity of representatives of the main classes of environmental contaminants of emerging concern, the triclopyr herbicides, 2,4-D and diuron, and the personal use product in cosmetics, decamethylcyclopentasiloxane (D5). The indicated experimental systems - cultivation of cells of different lineages in 2D, 3D and 3D bioprinting - will provide scientific information that will support the implementation of coherent and effective strategies to control these environmental contaminants. Additionally, the project will favor collaboration between researchers in the short and medium term, as the cell culture strategies proposed here could be used in other research in the field of Toxicology, Pharmacology and Pathology. Furthermore, the approval of this proposal will provide great development in the research line of the Toxicam Laboratory and aims to continue the research consolidated through the regular project (FAPESP 2018/00229-1). The activities to be developed are part of the research goals in strategic areas for the country, with regard to sustainable production, cleaner production and products suited to international standards aimed at environmental preservation and human health. In addition, they provide for the involvement of undergraduate and graduate students, providing them with knowledge of recently developed research methodologies, which are in line with international trends. (AU)

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