The first report on the assessment of maximum acceptable daily intake (MADI) of pesticides for humans using intelligent consensus predictions

Abstract

Direct or indirect consumption of pesticides and their related products by humans and other living organisms without safe dosing may pose a health risk. The risk may arise after a short/long time which depends on the nature and amount of chemicals consumed. Therefore, the maximum acceptable daily intake of chemicals must be calculated to prevent these risks. In the present work, regression-based quantitative structure–activity relationship (QSAR) models were developed using 39 pesticides with maximum acceptable daily intake (MADI) for humans as the endpoint. From the statistical results (R² = 0.674–0.712, Q_LOO² = 0.553–0.580, Q_(F1)² = 0.544–0.611, and Q_(F2)² = 0.531–0.599), it can be inferred that the developed models were robust, reliable, reproducible, accurate, and predictive. Intelligent Consensus Prediction (ICP) was employed to improve the external predictivity (Q_(F1)² =0.579–0.657 and Q_(F2)² = 0.563–0.647) of the models. Some of the chemical markers responsible for toxicity enhancement are the presence of unsaturated bonds, lipophilicity, presence of C< (double bond–single bond–single bonded carbon), and the presence of sulphur and phosphate bonds at the topological distances 1 and 6, while the presence of hydrophilic groups and short chain fragments reduces the toxicity. The Pesticide Properties Database (PPDB) (1694 pesticides) was also screened with the developed models. Hence, this research work will be helpful for the toxicity assessment of pesticides before their synthesis, the development of eco-friendly and safer pesticides, and data-gap filling reducing the time, cost, and animal experimentation. Thus, this study might hold promise for future potential MADI assessment of pesticides and provide a meaningful contribution to the field of risk assessment.