US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, Duluth, Minnesota, USA.
Environ Toxicol Chem. 2013 Jul;32(7):1611-22. doi: 10.1002/etc.2219. Epub 2013 May 28.
Models were developed to predict the bioconcentration of well-metabolized chemicals by rainbow trout. The models employ intrinsic clearance data from in vitro studies with liver S9 fractions or isolated hepatocytes to estimate a liver clearance rate, which is extrapolated to a whole-body biotransformation rate constant (kMET ). Estimated kMET values are then used as inputs to a mass-balance bioconcentration prediction model. An updated algorithm based on measured binding values in trout is used to predict unbound chemical fractions in blood, while other model parameters are designed to be representative of small fish typically used in whole-animal bioconcentration testing efforts. Overall model behavior was shown to be strongly dependent on the relative hydrophobicity of the test compound and assumed rate of in vitro activity. The results of a restricted sensitivity analysis highlight critical research needs and provide guidance on the use of in vitro biotransformation data in a tiered approach to bioaccumulation assessment.
建立了模型来预测代谢良好的化学物质在虹鳟鱼体内的生物浓缩情况。这些模型采用来自 S9 肝片段或分离肝细胞的体外研究的固有清除数据来估算肝清除率，然后将其外推至全身生物转化速率常数（kMET）。估计的 kMET 值随后用作质量平衡生物浓缩预测模型的输入。一种基于在虹鳟鱼中测量的结合值的更新算法用于预测血液中未结合的化学物质分数，而其他模型参数旨在代表通常用于整个动物生物浓缩测试的小鱼。整体模型行为被证明强烈依赖于测试化合物的相对疏水性和体外活性的假定速率。受限敏感性分析的结果突出了关键的研究需求，并为在分层生物积累评估方法中使用体外生物转化数据提供了指导。
