拓展等效线图法评估离子液体与杀菌剂多果定之间的拮抗作用

Extended Isobologram for Predicting Antagonism between Pyridiniumbased Ionic Liquids and Dodine

等效线图法(isobologram)是评估化学混合物毒性相互作用的经典方法之一,然而该方法仅能评估混合物在某一特殊浓度效应水平(通常为50%的浓度效应水平,即EC50)的联合毒性作用情况。因此,拓展等效线图法并用于不同效应水平下混合物毒性的评估显得尤为必要。以杀菌剂多果定(Dod)和3种离子液体(ILs)包括溴化丁基吡啶([bpy]Br)、溴化己基吡啶([hpy]Br)和溴化辛基吡啶([opy]Br)为混合物组分,采用直线均分射线法设计3组二元混合物体系(Dod-[bpy]Br、Dod-[hpy]Br和Dod-[opy]Br)共15条射线,应用微板毒性分析法系统测定各污染物及其混合物射线对青海弧菌Q67(Vibro qinghaisiense sp.Q67,Q67)的毒性,应用拓展等效线图法分析15条混合物射线在5个不同效应水平(EC20、EC30、EC40、EC50和EC60)的毒性相互作用,并与经典等效线图法和浓度加和模型(CA)评估的结果进行比较。结果表明:以pEC50为毒性指标,3种吡啶ILs对Q67的毒性具有烷基链效应,即毒性大小顺序为Dod-[opy]Br>Dod-[hpy]Br>Dod-[bpy]Br;3组二元混合物体系的15条射线的毒性,随农药Dod浓度比的减少而减弱;拓展等效线图法可以比较直观地表征3组Dod-ILs混合物体系在5个不同效应水平的拮抗作用,且拮抗作用强度随Dod浓度比的增加而变化,即先增强后减弱;拓展等效线图法可以有效地评估二元混合物在多个效应水平的联合毒性相互作用。

Isobologram is a classical graphical analysis method for the evaluation of toxicity interaction within chemical mixtures.However,the method can only evaluate the toxicity interaction within mixtures at some certain concentration-effect level (such as EC50 ).Therefore,it is necessary to extend the isobologram to evaluate mixture toxicity interaction at different effect levels.Three pyridinium-based ionic liquids (ILs),bromide butyl pyrimidine ([bpy]Br),bromide hexyl pyrimidine ([hpy]Br),bromide oxyl pyrimidine ([opy]Br) and a fungicide (Dodine,Dod), were selected as mixture components.Three binary mixture systems (Dod-[bpy]Br,Dod-[hpy]Br,Dod-[opy]Br) with 15 rays were designed by using the direct equipartition ray design procedure.The toxicity of single chemicals and their 15 binary mixture rays to Vibrio qinhaiensis sp.-Q67 were determined by the microplate toxicity analysis. The extended isobologram was used to analyze the joint toxicity interaction of the 15 rays at five different effect levels (EC20,EC30,EC40,EC50 and EC60 ).The obtained results were compared to those predicted by the classical isobologram and concentration addition (CA) model.The results showed that the toxicity of three ILs to Q67 had alkyl-side chain effect according to the negative logarithm of median effective concentration (pEC50 ).The toxicity of three binary mixture systems gradually reduced with concentration ratios of Dod in the mixture rays decreasing. The extended isobologram could well and clearly evaluate the toxicity interaction within three Dod-IL mixtures showing obviously antagonistic at 5 different effect levels.And the antagonistic effects firstly augmented and then weakened with the concentration ratio of Dod increasing.So the extended isobologram can effectively evaluate the joint toxicity interactions within binary mixtures.