Development of screening methodologies for chemical risk assessment: behavioral effects and neuropathological mechanisms in aquatic species

With the incessant growth of the chemical industry and the development of new molecules, there is an urgent need to evaluate the toxicity of many chemicals and their safe levels of exposure to ensure the protection of the environment and human health Currently, regulations on environmental risk assessment of chemicals are based on three main criteria for decision-making: lethality, growth, and reproduction. However, by adopting sublethal endpoints, such as considering changes in essential behaviors, we could improve the accuracy of risk assessment due to exposure to contaminants through the environment and, therefore, minimize these risks. This thesis focuses on developing effective screening strategies through methodological advancements and validation of behavioral assays in aquatic models, specifically zebrafish, Japanese medaka, and Daphnia magna. The methods outlined in this thesis are meticulously detailed to ensure reproducibility and ease of replication. Automation of tests and the use of video tools offer several advantages, including objective evaluations, reduced variability, and minimized error factors, facilitating their application in toxicological studies. The research initially explores the use of automated behavioral assays in the Daphnia magna model for screening emerging pollutants, particularly neuroactive drugs. Subsequently, behavioral assays are used to identify environmentally relevant adverse effects induced by insecticides in zebrafish larvae. Pharmacological validation and target profiling are employed to decipher potential modes of action. The thesis also investigates neurotoxic effects in adult zebrafish exposed to environmental levels of glyphosate and methamphetamine. Mechanistic approaches are utilized to understand adverse pathways leading to observed behavioral changes. Additionally, the zebrafish neurotoxidrome model is validated for testing potential therapeutic drugs, exemplified by N-acetyl cysteine’s protective effects against oxidative damage induced by acrylamide. Comparative toxicology analysis is employed to highlight similarities and differences in neurotoxic responses between organisms exposed to insecticides and a fungicide. The reproducibility of assays and the varying sensitivity of organisms to chemical compounds underscore the importance of studying multiple model organisms for comprehensive risk assessments. In conclusion, this thesis introduces innovative screening methodologies and provides valuable insights into chemical risk assessment in aquatic species. By incorporating behavior as a new endpoint in One Health assessments and extending research to non-mammalian models, it contributes to advancing toxicology, environmental conservation, and human health protection. These findings hold significant implications for regulatory frameworks, guiding decisions to ensure the safe and sustainable use of chemicals in our environment.

Peer reviewed