多效应残差法(MERA)表征二甲亚砜-农药二元混合物毒性相互作用

采用直接均分射线设计(EquRay)构建二甲亚砜(DMSO)分别与3种常用农药乐果(DIM)、敌敌畏(DIC)和甲霜灵(MET)的二元混合物,应用微板毒性分析(MTA)测试单个物质及混合物对青海弧菌Q67(Vibrio qinghaiensis sp.-Q67)的发光抑制毒性.以浓度加和(concentration addition,CA)模型检测混合物的毒性相互作用,提出并应用多效应残差法(multi-effectresidual analysis,MERA)定量表征DMSO-农药二元混合物实验观测毒性相对于CA模型预测结果的偏离程度,即毒性相互作用强度.表征结果显示3组DMSO-农药二元混合物的毒性相互作用以拮抗作用为主,最强拮抗作用在-23%～-15%之间,发生拮抗作用的浓度范围及拮抗作用强度受混合物组成、组分浓度比和效应水平等因素的影响.综合分析比较MERA与传统等效线图及扩展毒性单位和对3组二元混合物的表征结果发现,MERA从生物效应角度表征毒性相互作用强度,受到混合物组成和效应水平的限制较少,适用于分析具有复杂相互作用的二元混合物.

Characterizing the Toxicity Interaction of the Binary Mixture Between DMSO and Pesticide by the Multi-Effect Residual Analysis (MERA)

Three groups of binary mixtures between dimethylsulfoxide (DMSO) and three widely used pesticides, dimethoate (DIM), dichlorvos (DIC), and metalaxyl (MET), were respectively constructed by using the direct equipartition ray design (EquRay). The luminescent inhibition toxicities of single chemical and binary mixtures to Vibrio qinghaiensis sp.-Q67 were determined by the microplate toxicity analysis (MTA). Selecting the concentration addition (CA) model as an additive reference, we developed a new multi-effect residual analysis (MERA) to quantitatively characterize the deviation of the observed toxicity from that predicted by the CA model, i. e. the degree of toxicity interaction. It was shown that the toxicity interactions between DMSO and pesticide were dominated by antagonism, and the highest antagonism distributed between -23% and -15%. The concentration ranges where antagonism existed and the degree of antagonism were influenced by the components in the mixture, the concentration ratios of the components, and the effect level. A comparison of the MERA with the conventional isobologram and the extended toxic unit summation revealed that the MERA characterizes the degree of toxicity interaction in the view of effect, with less limitation by different concentration ratios or effect levels. Therefore, the MERA can be used to evaluate the complex toxicity interactions taking place in binary mixtures.