Internal concentrations (ICs) are crucial for linking exposure to effects in the development of New Approach Methodologies. ICs of chemicals in aquatic organisms are primarily driven by hydrophobicity and modulated by biotransformation and efflux. Comparing the predicted baseline to observed toxicity enables the estimation of effect specificity, but biological processes can lead to overestimating ICs and bias the specificity assessment. To evaluate the prediction of a mass balance model (MBM) and the impact of biotransformation on ICs, experimental ICs of 63 chemicals in zebrafish embryos were compared to predictions with physicochemical properties as input parameters. Experimental ICs of 79% (50 of 63) of the chemicals deviated less than 10-fold from predictions, and the remaining 13 deviated up to a factor of 90. Using experimental ICs changed the classification for 19 chemicals, with ICs 5 to 90 times lower than predicted, showing the bias of specificity classification. Uptake kinetics of pirinixic acid, genistein, dexamethasone, ethoprophos, atorvastatin, and niflumic acid were studied over a 96 h exposure period, and transformation products (TPs) were elucidated using suspect- and nontarget screening with UPLC-HRMS. 35 TPs (5 to 8 TPs per compound) were tentatively identified and semiquantified based on peak areas, suggesting that biotransformation may partly account for the overpredictions of ICs.

中文翻译：

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生物转化对斑马鱼胚胎中有机化学物质内部浓度和特异性分类的影响 （Danio rerio）


在开发新方法方法时，内部浓度 （IC） 对于将暴露与影响联系起来至关重要。水生生物中化学物质的 IC 主要由疏水性驱动，并受生物转化和外排调节。将预测的基线与观察到的毒性进行比较可以估计效应特异性，但生物过程可能导致高估 IC 并使特异性评估产生偏差。为了评估质量平衡模型 （MBM） 的预测和生物转化对 IC 的影响，将斑马鱼胚胎中 63 种化学物质的实验 IC 与以物理化学性质作为输入参数的预测进行了比较。79%（63 种中的 50 种）化学物质的实验 IC 与预测的偏差不到 10 倍，其余 13 种的偏差高达 90 倍。使用实验 IC 改变了 19 种化学品的分类，IC 比预测低 5 到 90 倍，显示出特异性分类的偏差。在 96 h 暴露期内研究了吡啶酸、染料木黄酮、地塞米松、依索磷、阿托伐他汀和尼氟酸的摄取动力学，并使用 UPLC-HRMS 的疑似和非靶向筛查阐明转化产物 （TPs）。初步鉴定了 35 个 TP （每种化合物 5 至 8 个 TP） 并根据峰面积进行了半定量，这表明生物转化可能部分解释了 IC 的高估。