Toward more useful in vitro toxicity data with measured free concentrations
Toward more useful in vitro toxicity data with measured free concentrations
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DOI：
10.1021/es049285w
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发表时间：
2004-12-01
影响因子：
11.4
通讯作者：
Hermens, JLM
中科院分区：
文献类型：
--
作者：
Heringa, MB;Schreurs, RHMM;Hermens, JLM
体外试验和计算机模型是体内动物试验的有前途的替代方法，但这些替代方法预测体内风险的能力仍然非常有限。向前迈出的一步是使体外测定的结果（如中位效应浓度（EC50值））与测定条件（如蛋白质含量）无关。在这里，我们表明，在体外试验介质中的化学品的测量游离浓度的结果在系统独立的EC50值。我们介绍了一种非常简单的方法来测量自由浓度在微型测试系统中使用可忽略耗尽固相微萃取。生成的数据更适合于外推到体内，为计算方法提供无偏输入（例如，定量结构活性关系），并且可以对环境污染物的活性提供完全不同的见解。
In vitro assays and computer models are promising alternatives for in vivo animal testing, but the power of these alternative methods to predict in vivo risk is still very limited. One step forward is to make the outcome of in vitro assays (such as median effect concentrations (EC50 values)) independent of assay conditions such as protein content. Here we show that measured free concentrations of chemicals in the in vitro assay medium result in system independent EC50 values. We introduce a very simple method to measure free concentrations in miniature test systems using negligible depletion solid-phase microextraction. The generated data are much more suitable for extrapolation to in vivo, provide unbiased input for computational methods (for example, quantitative structure activity relationships), and can shed an entirely different light on the activity of environmental contaminants.