Chemometric modeling of plant protection products (PPPs) for the prediction of acute contact toxicity against honey bees (A. mellifera): A 2D-QSAR approach

Abstract

Honey bees (Apis mellifera) are vital for economic, viable agriculture and for food safety. Although Plant Protection Products (PPPs) are of undeniable importance in the global agricultural system, these have become potential threats for non-target organisms like pollinators (e.g., honey bees etc.), resulting in the disruption of the ecological balance. In the current work, we have used the 113 PPP analogs to develop a 2D-QSAR model and explored the structural features modulating the toxic effects on honey bees, following the Organization for Economic Co-operation and Development (OECD) guidelines. The extensive validation of the developed model has been performed using internal and external validation metrics to make sure that the model is statistically sound and interpretable enough to be acceptable. The obtained results (R² = 0.666, Q² = 0.594, Q²_F1 = 0.647 and Q²_F2 = 0.646) determine the predictability and reliability of the developed model. This model should be useful for the predictions (acute contact toxicity (LD₅₀)) of the new and untested compounds located inside the applicability domain of the developed model. Moreover, we have performed the in-silico prediction of toxicity against honey bees of a total of 709 compounds obtained from the pesticide properties database (PPDB) using the developed model.

Keywords: In silico; OECD; PPPs; QSAR; Validation.