Prediction and assessment of the effects of mixtures of four xenoestrogens.
Prediction and assessment of the effects of mixtures of four xenoestrogens.
复制标题
DOI：
10.1289/ehp.00108983
复制
发表时间：
2000-10
影响因子：
10.4
通讯作者：
Kortenkamp, A
中科院分区：
文献类型：
--
作者：
Payne, J;Rajapakse, N;Wilkins, M;Kortenkamp, A
雌激素类药物混合效应的评价是世界各国政府机构和专家决策机构高度重视的问题。然而，迄今为止发表的少数混合物研究受到概念和实验问题的困扰，被认为是不确定的。在这里，我们报告的两种，三种和四种成分的o，p '-滴滴涕，染料木素，4-壬基酚，4-正辛基酚，所有化合物的雌激素活性有充分的证据的混合物的评估结果。使用重组酵母筛选（酵母雌激素筛选，是）对单一药物进行了广泛的浓度响应分析。基于YES试验中单一药物的活性，我们计算了我们所选试验药物混合物的整个浓度-响应曲线的预测值（假设存在加性组合效应）。为了这个目的，我们采用了浓度加成和独立作用的模型，这两个模型都是用于计算混合物效应的成熟模型。实验浓度响应分析显示，在所有情况下，预测和观察到的混合物效应之间的良好协议。我们的研究结果表明，o，p '-DDT，染料木素，4-壬基酚，和4-正辛基酚在YES测定中的组合效果不偏离预期的加和性。我们认为这两个参考模型作为有用的工具，用于评估多种混合物的异种雌激素的组合效应。
The assessment of mixture effects of estrogenic agents is regarded as an issue of high priority by many governmental agencies and expert decision-making bodies all over the world. However, the few mixture studies published so far have suffered from conceptual and experimental problems and are considered to be inconclusive. Here, we report the results of assessments of two-, three- and four-component mixtures of o,p'-DDT, genistein, 4-nonylphenol, and 4-n-octylphenol, all compounds with well-documented estrogenic activity. Extensive concentration-response analyses with the single agents were carried out using a recombinant yeast screen (yeast estrogen screen, YES). Based on the activity of the single agents in the YES assay we calculated predictions of entire concentration-response curves for mixtures of our chosen test agents assuming additive combination effects. For this purpose we employed the models of concentration addition and independent action, both well-established models for the calculation of mixture effects. Experimental concentration-response analyses revealed good agreement between predicted and observed mixture effects in all cases. Our results show that the combined effect of o,p'-DDT, genistein, 4-nonylphenol, and 4-n-octylphenol in the YES assay does not deviate from expected additivity. We consider both reference models as useful tools for the assessment of combination effects of multiple mixtures of xenoestrogens.