In Silico Ecotoxicological Modeling of Pesticide Metabolites and Mixtures

Prior to registration, careful assessment of transformation products (TPs) that are more toxic than their parent compounds is required, and EU regulations require greater use of non-animal test methods and risk assessment strategies. Predicting the toxicity of transformation products and chemical mixtures is a major challenge for modern toxicology. Since the metabolic processes of transformation products and toxic effects of chemical mixtures involve complex mechanisms, it is essential to use in silico modeling methods to consider different chemico-biological interactions of metabolic transformation and mixture toxicity. This chapter reviews previous modeling methods used to study pesticide metabolites and mixtures. Although various metabolites are emitted into the environment, there are few ways to interpret metabolites by predicting their ecotoxicological potential, so their formation and environmental fate are largely unknown. In vitro testing has limited coverage of metabolic processes present throughout the organism and may not always predict in vivo results. For systematically assessing the metabolic activation of persistent organic pollutants, researchers designed a comprehensive metabolic simulator to generate the metabolic profile of the POPs. In order to analyze and evaluate parent compounds and transformation products in the environment, data generation based on quantitative structure-activity relationship (QSAR) is becoming more and more important. Besides these, a process-based multimedia multi-species model allows us to quantitatively estimate the environmental exposure and fate of parent compounds and transformation products. Pollutants in the environment usually appear in a joint form, and the biological effects of the mixture are different from the single separated components, so the risk assessment criteria for a single compound cannot accurately infer the actual complex environmental assessment. The interaction between the components of the mixture promotes significant changes in compositional characteristics and complications leading to synergistic or antagonistic effects. The covalent bonding, ionic bonding, van der Waals force, and hydrophilicity are important intermolecular forces that affect the interaction of chemical mixtures and are associated with four types of descriptors. This relationship has been able to study the reaction mechanisms of various environmental characteristics of organic pollutants.