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首页> 外文期刊>Environmental Science & Technology >Understanding Receptor-Mediated Effects in Rainbow Trout: In Vitro-in Vivo Extrapolation Using Physiologically Based Toxicokinetic Models
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Understanding Receptor-Mediated Effects in Rainbow Trout: In Vitro-in Vivo Extrapolation Using Physiologically Based Toxicokinetic Models

机译：了解虹鳟中受体介导的作用：使用基于生理学的毒代动力学模型进行体内体外推断

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摘要

The European REACH regulation requires the use of animal experimentation to assess the risk of industrial chemicals. However, the 3R principle (reduction, replacement, refinement) demands the use of suitable alternative test methods. Many dossiers submitted for the authorization of chemicals have attempted to provide the required data without performing new experiments, relying heavily on in silico methods; in vitro assays were scarcely used. We propose a methodology that uses physiologically based toxicokinetic (PBTK) models to extrapolate in vitro data to the in vivo level. We collected experimental results for in vitro and in vivo ethoxyresorufin-O-deethylase and vitellogenin induction following chemical exposure and compared those results with model predictions. We found that the predictive power of aqueous chemical concentrations was limited; median effect concentrations (EC50s) based on internal concentrations in fish correlated better with in vitro EC50s. Our data show that in vitro assays could offer a substitute for fish studies when combined with PBTK models.
机译：欧洲REACH法规要求使用动物实验来评估工业化学品的风险。但是，3R原则（减少，替换，改进）要求使用合适的替代测试方法。提交的许多用于化学药品授权的档案试图在不进行新实验的情况下提供所需的数据，这在很大程度上依赖计算机方法。很少使用体外测定。我们提出了一种方法，该方法使用基于生理的毒代动力学（PBTK）模型将体外数据外推到体内水平。在化学暴露后，我们收集了体外和体内乙氧基试卤灵-O-脱乙基酶和卵黄蛋白原诱导的实验结果，并将这些结果与模型预测值进行了比较。我们发现含水化学物浓度的预测能力是有限的。基于鱼类内部浓度的中位效应浓度（EC50s）与体外EC50更好地相关。我们的数据表明，与PBTK模型结合使用时，体外分析可以代替鱼类研究。

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  • 来源
    《Environmental Science & Technology》 |2014年第6期|3303-3309|共7页
  • 作者

    Markus Brinkmann; Kathrin Eichbaum; Sebastian Buchinger; Georg Reifferscheid; Thuy Bui; Andreas Schaeffer; Henner Hollert; Thomas G. Preuss;

  • 作者单位

    Department of Ecosystem Analysis, RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen, North Rhine-Westphalia, Germany;

    Department of Ecosystem Analysis, RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen, North Rhine-Westphalia, Germany;

    Department G3: Biochemistry, Ecotoxicology, Federal Institute of Hydrology (BfG), Am Mainzer Tor 1, 56068 Koblenz, Rhineland-Palatinate, Germany;

    Department G3: Biochemistry, Ecotoxicology, Federal Institute of Hydrology (BfG), Am Mainzer Tor 1, 56068 Koblenz, Rhineland-Palatinate, Germany;

    Chair of Environmental Biology and Chemodynamics, RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen, North Rhine-Westphalia, Germany;

    Chair of Environmental Biology and Chemodynamics, RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen, North Rhine-Westphalia, Germany ,State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210093, China;

    Department of Ecosystem Analysis, RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen, North Rhine-Westphalia, Germany ,State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210093, China ,College of Resources and Environmental Science, Chongqing University, Chongqing 400044, China ,College of Environmental Science and Engineering and State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, Shanghai 200092, China;

    Chair of Environmental Biology and Chemodynamics, RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen, North Rhine-Westphalia, Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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