QSAR models for the acute toxicity of 1,2,4-triazole fungicides to zebrafish (Danio rerio) embryos

Abstract

In recent decades, the 1,2,4-triazole fungicides are widely used for crop diseases control, and their toxicity to wild lives and pollution to ecosystem have attracted more and more attention. However, how to quickly and efficiently evaluate the toxicity of these compounds to environmental organisms is still a challenge. In silico method, such like Quantitative Structure-Activity Relationship (QSAR), provides a good alternative to evaluate the environmental toxicity of a large number of chemicals. At the present study, the acute toxicity of 23 1,2,4-triazole fungicides to zebrafish (Danio rerio) embryos was firstly tested, and the LC50 (median lethal concentration) values were used as the bio-activity endpoint to conduct QSAR modelling for these triazoles. After the comparative study of several QSAR models, the 2D-QSAR model was finally constructed using the stepwise multiple linear regression algorithm combining with two physicochemical parameters (logD and μ), an electronic parameter (QN1) and a topological parameter (XvPC4). The optimal model could be mathematically described as following: pLC50 = −7.24–0.30XvPC4 + 0.76logD - 26.15QN1 - 0.08μ. The internal validation by leave-one-out (LOO) cross-validation showed that the R2adj (adjusted noncross-validation squared correlation coefficient), Q2 (cross-validation correlation coefficient) and RMSD (root-mean-square error) was 0.88, 0.84 and 0.17, respectively. The external validation indicated the model had a robust predictability with the q2 (predictive squared correlation coefficient) of 0.90 when eliminated tricyclazole. The present study provided a potential tool for predicting the acute toxicity of new 1,2,4-triazole fungicides which contained an independent triazole ring group in their molecules to zebrafish embryos, and also provided a reference for the development of more environmentally-friendly 1,2,4-triazole pesticides in the future.