Chemometrics-driven prediction and prioritization of diverse pesticides on chickens for addressing hazardous effects on public health

The extensive use of various pesticides in the agriculture field badly affects both chickens and humans, primarily through residues in food products and environmental exposure. This study offers the first quantitative structure-toxicity relationship (QSTR) and quantitative read-across-structure toxicity relationship (q-RASTR) models encompassing the LOEL and NOEL endpoints for acute toxicity in chicken, a widely consumed protein. The study's significance lies in the direct link between chemical toxicity in chicken, human intake, and environmental damage. Both the QSTR and the similarity-based read-across algorithms are applied concurrently to improve the predictability of the models. The q-RASTR model was generated by combining read-across derived similarity and error-based parameters, alongside structural and physicochemical descriptors. Machine Learning approaches (SVM and RR) were also employed with the optimization of relevant hyperparameters based on the cross-validation approach, and the final test set prediction results were compared. The PLS q-RASTR models for NOEL and LOEL endpoints showed good statistical performance, as traced from the external validation metrics Q2F1: 0.762-0.844; Q2F2: 0.759-0.831 and MAEtest: 0.195-0.214. The developed models were further used to screen the Pesticide Properties DataBase (PPDB) for potential toxicants in chickens. Thus, established models can address eco-toxicological data gaps and development of novel and safe eco-friendly pesticides. The study's importance lies in the direct link between chemical toxicity in chicken, human intake, and environmental damage. Identifying and evaluating compound toxicity is crucial in managing adverse effects, including carcinogenicity, genotoxicity, immunotoxicology, reproductive and developmental toxicity, and safeguarding of avian species as well as public health. To overcome limitations like animal testing, time, cost, and limited experimental data, the developed PLS q-RASTR model can serve as a valuable tool for predicting toxicity effectively. The predictive model, along with the key structural insights gained in the present study, can contribute to developing environmentally friendly and safer chemicals, filling data gaps, and promoting the responsible use of ecotoxic substances.