Predicting the Time-Dependent Toxicities of Binary Mixtures of Five Antibiotics to Vibrio qinghaiensis sp.-Q67 Based on the QSAR Model  

作　　者：Xiachangli Xu Yongan Liu Lingyun Mo Xuehua Li Junfeng Dai Litang Qin 

机构地区：[1]College of Environmental Science and Engineering,Guilin University of Technology,Guilin 541004,China [2]Guangxi Key Laboratory of Theory and Technology for Environmental Pollution Control,Guilin 541006,China [3]Collaborative Innovation Center for Water Pollution Control and Water Safety in Karst Area,Guilin University of Technology,Guilin 541006,China [4]Key Laboratory of Industrial Ecological and Environmental Engineering(MOE),School of Environmental Science and Technology,Dalian University of Technology,Linggong Road 2,Dalian 116024,China

出　　处：《Environment & Health》2024年第7期465-473,共9页环境与健康（英文）

基　　金：National Natural Science Foundation of China(No.22266012);Guangxi Key Research and Development Program(Guike-AB23026045);Guilin Science and Technology Program(20220114-2);Guangxi Engineering Research Center of Comprehensive Treatment for Agricultural Non-Point Source Pollution;Modern Industry College of Ecology and Environmental Protection,Guilin University of Technology.

摘　　要：Antibiotics may be exposed in a mixed state in natural environments.The toxicity of antibiotic mixtures exhibits time-dependent characteristics,and data on the time-dependent toxicity of antibiotic mixtures is also relatively lacking.In this study,the toxicities of 45 binary mixtures composed of five antibiotics were investigated against Vibrio qinghaiensis sp.-Q67(Q67)at multiple exposure times(4,6,8,10,and 12 h).Quantitative structure–activity relationship(QSAR)models were developed for predicting the time-dependent toxicities of 45 binary mixtures.The results showed that the best QSAR models presented coefficient of determination(R2)of(0.818–0.913)and explained variance in prediction leave-one-out(Q2LOO)of(0.781–0.894)and predictive ability(Q2F1,Q2F2,Q2F3>0.682,concordance correlation coefficient>0.859).The R2 values of QSAR models outperformed the R2(0.628–0.810)of the conventional concentration addition models and the R2(0.654–0.792)of the independent action models.Furthermore,the QSAR models showed higher R2 and Q2LOO values at 4 h compared to other exposure times.Specifically,the model at the 30%effective concentration(EC30)had R2 of 0.902 and Q2LOO of 0.883,while the model at the 50%effective concentration(EC50)had R2 of 0.913 and Q2LOO of 0.894.The CATS2D_04_DP descriptor was found to be the most dominant and negatively correlated factor influencing the toxicity of mixed antibiotics against Q67 in the nine QSAR models developed over five exposure times.The reduction in the number of DP pharmacophore point pairs with a topological distance of 4 in the represented molecules is the primary cause for the rise in the time-dependent toxicity of the antibiotics against Q67.

关 键 词：ANTIBIOTICS Q67 QSAR model time-dependent toxicity toxicities prediction 

分 类 号：R12[医药卫生—环境卫生学] X5[医药卫生—公共卫生与预防医学]