Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou, 511443, China.
Department of Environmental Science, Institute of Biomedical Studies, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, Texas 76798, United States.
Environ Sci Technol. 2022 Aug 16;56(16):11547-11558. doi: 10.1021/acs.est.2c03421. Epub 2022 Jul 27.
Chemicals with elevated bioaccumulation profiles present potential hazards to public health and the environment. Ionizable organic compounds (IOCs) increasingly represent a large proportion of commercial chemicals; however, historical approaches for bioaccumulation determinations are mainly developed for neutral chemicals, which were not appropriate for IOCs. Herein, we employed the zebrafish embryo, a common vertebrate model in environmental and biomedical studies, to elucidate toxicokinetics and bioconcentration of eight IOCs with diverse physicochemical properties and pharmacokinetic parameters. At an environmentally relevant pH (7.5), most IOCs exhibited rapid uptake and depuration in zebrafish, suggesting the ionized forms of IOCs are readily bioavailable. Bioconcentration factors (BCF) of these IOCs ranged from 0.0530 to 250 L·kg wet weight. The human pharmacokinetic proportionality factor, apparent volume of distribution (), better predicted the BCF of selected IOCs than more commonly used hydrophobicity-based parameters (e.g., pH-dependent octanol-water distribution ratio, ). Predictive bioaccumulation models for IOCs were constructed and validated using alone or with . Significant relationships between fish BCF and human , which is readily available for pharmaceuticals, highlighted the utility of biologically based "read-across" approaches for predicting bioaccumulative potential of IOCs. Our novel findings thus provided an understanding of the partitioning behavior and improved predictive bioconcentration modeling for IOCs.
具有高生物积累特征的化学物质对公共健康和环境构成潜在危害。可离子化有机化合物（IOCs）越来越多地代表了商业化学物质的很大一部分；然而，生物积累测定的历史方法主要是为中性化学物质开发的，而这些方法并不适用于 IOCs。在此，我们采用斑马鱼胚胎作为环境和生物医学研究中的常见脊椎动物模型，阐明了 8 种具有不同物理化学性质和药代动力学参数的 IOCs 的毒代动力学和生物浓缩特性。在环境相关的 pH 值（7.5）下，大多数 IOCs 在斑马鱼中表现出快速的摄取和消除，表明 IOCs 的离子形式易于生物利用。这些 IOCs 的生物浓缩因子（BCF）范围从 0.0530 到 250 L·kg 湿重。与更常用的基于疏水性的参数（如 pH 依赖性辛醇-水分配比，）相比，人类药代动力学比例因子（）更好地预测了选定 IOCs 的 BCF。使用 或 构建和验证了 IOCs 的预测生物积累模型。鱼类 BCF 与人类 的显著相关性，后者易于获得药物，突出了基于生物学的“读通”方法在预测 IOCs 的生物积累潜力方面的实用性。因此，我们的新发现为理解 IOCs 的分配行为和改进预测生物浓缩建模提供了依据。
