Predictive Quantitative Read-Across Structure–Property Relationship Modeling of the Retention Time (Log<i>t</i><sub>R</sub>) of Pesticide Residues Present in Foods and Vegetables
Shilpayan Ghosh, Mainak Chatterjee, Kunal Roy
Abstract
The retention time (log t R ) of pesticidal compounds in a reverse-phase high-performance liquid chromatography (HPLC) analysis has a direct relationship with lipophilicity, which could be related to the ecotoxicity potential of the compounds. The novel quantitative read-across structure–property relationship (q-RASPR) modeling approach uses similarity-based descriptors for predictive model generation. These models have been shown to enhance external predictivity in previous studies for several end points. The current study describes the development of a q-RASPR model using experimental retention time data (log t R ) in the HPLC experiments of 823 environmentally significant pesticide residues collected from a large compound database. To model the retention time (log t R ) end point, 0D–2D descriptors have been used along with the read-across-derived similarity descriptors. The developed partial least squares (PLS) model was rigorously validated by various internal and external validation metrics as recommended by the Organization for Economic Co-operation and Development (OECD). The final q-RASPR model is proven to be a good fit, robust, and externally predictive ( n train = 618, R 2 = 0.82, Q 2 LOO = 0.81, n test = 205, and Q 2 F1 = 0.84) that literally outperforms the external predictivity of the previously reported quantitative structure–property relationship (QSPR) model. From the insights of modeled descriptors, lipophilicity is found to be the most important chemical property, which positively correlates with the retention time (log t R ). Various other characteristics, such as the number of multiple bonds (nBM), graph density (GD), etc., have a substantial and inversely proportionate relationship with the retention time end point. The software tools utilized in this study are user-friendly, and most of them are free, which makes our methodology quite cost-effective when compared to experimentation. In a nutshell, to obtain better external predictivity, interpretability, and transferability, q-RASPR is an efficient technique that has the potential to be employed as a good alternative approach for retention time prediction and ecotoxicity potential identification.