Predictive Quantitative Read-Across Structure-Property Relationship Modeling of the Retention Time (Log t R ) of Pesticide Residues Present in Foods and Vegetables.

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.