A Computational Approach to Mechanistic and Predictive Toxicology of Pesticides

The study explored a computational systems toxicology approach to understand the modes of action of five pesticides: prochloraz, tebuconazole, epoxiconazole, procymidone, and mancozeb. By analyzing human proteins associated with these pesticides and integrating protein-disease information, the researchers identified that the primary human adverse effects were reproductive disorders and adrenal diseases. Prochloraz, tebuconazole, and procymidone primarily affected steroidogenesis and nuclear receptors, with prochloraz and tebuconazole significantly linked to testicular dysgenesis syndrome. Mancozeb exhibited a different mode of action involving inflammatory processes. This method allowed for efficient data analysis and chemical grouping based on their modes of action and potential human health effects, aiding in predicting the effects of chemical mixtures and contributing to the development of adverse outcome pathways.