Toxicity prediction of 1,2,4-triazoles compounds by QSTR and interspecies QSTTR models

• Published in: Ecotoxicology and environmental safety Vol. 242; p. 113839
• Main Authors: Liu, Zhiyong, Dang, Kai, Gao, Junhong, Fan, Peng, Li, Cunzhi, Wang, Hong, Li, Huan, Deng, Xiaoni, Gao, Yongchao, Qian, Airong
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2022; Elsevier
• Subjects: 4-triazoles; Acute toxicity; IQSTTR; QSTR; Validation; Validation; 1; 2; 4-triazoles; QSTR; IQSTTR; Acute toxicity
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2022.113839

1,2,4-triazole derivatives exhibit various biological activities, including antibacterial and antifungal properties. On the other hand, these chemicals may have unique cumulative and harmful effects on living organisms. The goal of this work is to use quantitative structure-toxicity relationship (QSTR) and interspecies quantitative toxicity-toxicity relationship (iQSTTR) models to predict the acute toxicity of 1,2,4-triazole derivatives. The QSTR models were generated by multiple linear regression (MLR) following the OECD recommendations for QSAR model development and validation. The iQSTTR models were constructed using data on acute oral toxicity in rats and mice, as well as the 2D descriptor. The application domain (AD) analysis was used to identify model outliers and determine if the forecast was credible. Six QSTR models were successfully constructed in rats and mice using various delivery methods, and the scatter plots demonstrated excellent consistency across training and test sets. According to external and internal validation criteria, all six QSTR models may be broadly accepted; however, the orally administered mice model was the optimum one among the six species. Several chemicals with leverage values above the requirements were identified as response or structural outliers in the training sets for six QSTR and two iQSTTR models. All outliers, however, fell slightly outside the threshold or had low prediction errors, which may have had little impact on the capacity to forecast and were therefore preserved in the final models. In fact, neither the QSTR nor the iQSTTR test sets contained any response outliers. Additionally, all external and internal validation results for the iQSTTR models were approved, with the iQSTTR models outperforming the comparable QSTR models, which are deemed more dependable. The QSTR and iQSTTR models performed well in predicting toxicity using test sets, which would be beneficial in evaluating and synthesizing newly discovered 1,2,4-triazoles derivatives with low toxicity and environmental hazard. [Display omitted] •GA-MLR algorithms were used to construct the QSTR and iQSTTR models.•This is the first report to predict the acute toxicity of mammalian animals against 1,2,4-triazole derivatives.•Six QSTR models for a single administration route to rodents were successfully developed.•Several validation criteria evaluated the models according to the OECD principles.