Department of Analytical Chemistry, Faculty of Chemical Science, Complutense University of Madrid, Avenida Complutense s/n, 28040, Madrid, Spain.
Chemosphere. 2024 Sep;364:143020. doi: 10.1016/j.chemosphere.2024.143020. Epub 2024 Aug 3.
The application of the 3Rs (Replacement, Reduction, and Refinement) in animal experimentation has recently concentrated its efforts on utilizing cellular systems to predict toxicity in organisms. In this context, while refining the data obtained from cell lines, this study assesses their bioaccumulation potential and various methods for extrapolating the in vitro metabolization rate constant to support modelled bioaccumulation assessments for fish and their limitations. For this purpose, the concentrations of the parent compound, phenanthrene, and its major metabolites within the cells and in the medium at various exposure times were quantified. A chemical distribution model (mass balance) was applied to calculate the concentrations of the cell-bioaccessible compounds (C) based on the experimentally determined concentrations. An elevated matching was observed between the in vitro bioconcentration factor (BCF) and the in vivo BCFs reported in the literature for zebrafish liver cells (ZFL). This study demonstrates the importance of further investigating in vitro biotransformation kinetics. The results obtained with the approach developed here provide valuable information to enhance current models. Additionally, it underscores the potential of cell lines as a strategy for rapid, simple, and cost-effective predictions without the need for animal experimentation.
3R（替代、减少和优化）在动物实验中的应用最近集中精力利用细胞系统来预测生物体的毒性。在这种情况下，本研究在优化从细胞系获得的数据的同时，评估了它们的生物累积潜力以及将体外代谢率常数外推以支持鱼类模型生物累积评估的各种方法及其局限性。为此，定量了在不同暴露时间下细胞内和培养基中母体化合物菲和其主要代谢物的浓度。应用化学分配模型（质量平衡）根据实验确定的浓度计算细胞可利用化合物的浓度（C）。在体外生物浓缩因子（BCF）与文献中报道的斑马鱼肝细胞（ZFL）的体内 BCF 之间观察到高度匹配。本研究证明了进一步研究体外生物转化动力学的重要性。此处开发的方法获得的结果提供了有价值的信息，可增强现有模型。此外，它强调了细胞系作为一种快速、简单且具有成本效益的预测策略的潜力，而无需进行动物实验。
