Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai, 200092, PR China.
Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, PR China; State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, PR China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai, 200092, PR China.
Environ Pollut. 2021 Oct 1;286:117207. doi: 10.1016/j.envpol.2021.117207. Epub 2021 May 3.
Studies have shown that the mixture toxicity of compounds with similar modes of action (MOAs) is usually predicted by the concentration addition (CA) model. However, due to the lack of toxicological information on compounds, more evidence is needed to determine whether the above conclusion is generally applicable. In general, the same type of compounds with similar chemical structures have similar MOAs, so whether the toxicities of the mixture of these compounds are additive needs to be further studied. In this paper, three types of pesticides with similar chemical structures (three organophosphoruses, two carbamates and two neonicotinoids) that may have similar MOAs were selected and five binary mixture systems were constructed. For each system, five mixture rays with different concentration ratios were designed by the direct equipartition ray design (EquRay) method. The mortality of Caenorhabditis elegans was regarded as the endpoint for the toxicity exposure to single pesticides and binary mixtures. The combined toxicities were evaluated simultaneously using the CA model, isobologram and combination index. The structural similarity of the same type of pesticides was quantitatively analyzed according to the MACCS molecular fingerprint and the slope of dose-response curve at pEC. The results show that the toxicities of neonicotinoid mixtures and carbamate mixtures are almost antagonistic. The entire mixture system of dichlorvos and dimethoate produced synergism, and four of the five mixture rays of dimethoate and methamidophos induced antagonism, while among the mixture rays of dichlorvos and methamidophos, different concentrations showed different interaction types. The results of structural similarity analysis show that the size of structural similarity showed a certain quantitative relationship with the toxicity interaction of mixtures, that is, the structural similarity of the same type of pesticides may show an additive action in a certain range.
研究表明，具有相似作用模式（MOA）的化合物混合物的毒性通常可以通过浓度加和（CA）模型来预测。然而，由于缺乏关于化合物的毒理学信息，需要更多的证据来确定上述结论是否普遍适用。一般来说，具有相似化学结构的同类化合物具有相似的 MOA，因此这些化合物混合物的毒性是否具有加和性需要进一步研究。本文选择了三种具有相似化学结构（三种有机磷、两种氨基甲酸酯和两种新烟碱类）的农药，它们可能具有相似的 MOA，并构建了五个二元混合物体系。对于每个体系，通过直接等分射线设计（EquRay）方法设计了五个不同浓度比的混合物射线。用秀丽隐杆线虫的死亡率作为单一农药和二元混合物暴露的毒性终点。利用 CA 模型、等对数图和组合指数同时评价联合毒性。根据 MACCS 分子指纹和 pEC 处剂量-反应曲线的斜率，对同类型农药的结构相似性进行定量分析。结果表明，新烟碱类混合物和氨基甲酸酯类混合物的毒性几乎呈拮抗作用。敌敌畏和乐果的整个混合物体系产生协同作用，乐果和甲胺磷的五个混合物射线中的四个产生拮抗作用，而敌敌畏和甲胺磷的混合物射线中，不同浓度表现出不同的相互作用类型。结构相似性分析结果表明，结构相似性的大小与混合物的毒性相互作用呈一定的定量关系，即同类型农药的结构相似性在一定范围内可能表现出相加作用。
