A computational approach to mechanistic and predictive toxicology of pesticides

The study applied an integrated systems toxicology approach to analyze the modes of action of five pesticides—prochloraz, tebuconazole, epoxiconazole, procymidone, and mancozeb—on human health. By examining human proteins associated with these pesticides and enriching them with a human protein interactome, the researchers identified that the primary adverse effects were reproductive disorders and adrenal diseases. Prochloraz, tebuconazole, and procymidone mainly interfered with steroidogenesis and nuclear receptors, with prochloraz and tebuconazole significantly linked to Testicular Dysgenesis Syndrome. Mancozeb had a different mode of action, involving inflammatory processes. This computational method effectively grouped chemicals by their modes of action and potential adverse effects, aiding in predicting the effects of chemical mixtures and contributing to the development of adverse outcome pathways.