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首页> 外文期刊>Environmental toxicology and chemistry >A REVIEW OF INDEPENDENT ACTION COMPARED TO CONCENTRATION ADDITION AS REFERENCE MODELS FOR MIXTURES OF COMPOUNDS WITH DIFFERENT MOLECULAR TARGET SITES
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A REVIEW OF INDEPENDENT ACTION COMPARED TO CONCENTRATION ADDITION AS REFERENCE MODELS FOR MIXTURES OF COMPOUNDS WITH DIFFERENT MOLECULAR TARGET SITES

机译：与针对不同分子靶点的化合物混合物的浓度模型作为浓度模型的独立作用的综述

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摘要

From a theoretical point of view, it has often been argued that the model of independent action (IA) is the most correct reference model to use for predicting the joint effect of mixtures of chemicals with different molecular target sites. The theory of IA, however, relies on a number of assumptions that are rarely fulfilled in practice. It has even been argued that, theoretically, the concentration addition (CA) model could be just as correct. In the present study, we tested the accuracy of both IA and CA in describing binary dose-response surfaces of chemicals with different molecular targets using statistical software. We compared the two models to determine which best describes data for 158 data sets. The data sets represented 98 different mixtures of, primarily, pesticides and Pharmaceuticals tested on one or several of seven test systems containing one of the following: Vibrio fischeri, activated sludge microorganisms, Daphnia magna, Pseudokirchneriella subcapitata, Lemna minor, Tripleurospermum inodorum, or Stellaria media. The analyses showed that approximately 20% of the mixtures were adequately predicted only by IA, 10% were adequately predicted only by CA, and both models could predict the outcome of another 20% of the experiment. Half of the experiments could not be correctly described with either of the two models. When quantifying the maximal difference between modeled synergy or antagonism and the reference model predictions at a 50% effect concentration, neither of the models proved significantly better than the other. Thus, neither model can be selected over the other on the basis of accuracy alone.
机译：从理论角度来看，经常有人争辩说，独立作用模型（IA）是最正确的参考模型，可用于预测具有不同分子目标部位的化学物质混合物的联合作用。但是，IA的理论基于许多在实践中很少能实现的假设。甚至有人认为，从理论上讲，浓度增加（CA）模型可能是正确的。在本研究中，我们使用统计软件测试了IA和CA在描述具有不同分子靶标的化学物质的二元剂量反应表面时的准确性。我们比较了两个模型，以确定哪种模型最能描述158个数据集的数据。这些数据集代表98种不同的农药和药物混合物，主要是在以下测试系统中的一种或几种中测试的，这些系统包含以下之一：费氏弧菌，活化的污泥微生物，大水蚤，小假单胞菌，小Lemna，无臭三倍精子或斯特拉氏菌媒体。分析表明，只有IA可以充分预测约20％的混合物，仅CA可以充分预测约10％的混合物，并且两种模型都可以预测另外20％的实验结果。两种模型都无法正确描述一半的实验。当在50％的作用浓度下对建模的协同作用或拮抗作用与参考模型预测之间的最大差异进行量化时，这两个模型都没有明显优于另一个模型。因此，仅凭准确性就无法选择任何一个模型。

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