Dietary uptake plays an important role in fish bioaccumulation of per- and polyfluoroalkyl substances (PFAS). However, the existing toxicokinetic modeling for dietary uptake of PFAS is limited. In this study, adult zebrafish were exposed to diet-borne PFAS with diverse structures for 3 days, followed by a 12 day depuration. The PFAS levels in zebrafish were monitored and predicted by toxicokinetic models. The experimental results showed intermittent feeding caused a peak PFAS level during feeding intervals. A two-compartment model considering intermittent feeding can accurately describe the dietary uptake kinetics of PFAS and provide a robust estimation of assimilation efficiency. The extent of PFAS level fluctuation is determined by the elimination rate constant in the whole body. Subsequently, a physiologically based toxicokinetic (PBTK) model considering intermittent dietary uptake was developed to predict the internal body burden and tissue distribution of PFAS in zebrafish. The incorporation of intermittent feeding into the PBTK model significantly enhanced the model performance and provided PFAS level estimates within a factor of 2 for most of the experimental measurements during exposure. This study underscores the significant influence of intermittent dietary uptake on the internal body burden of PFAS in fish and advocates for its integration within the toxicokinetic model framework.

中文翻译：

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斑马鱼间歇性膳食吸收全氟烷基和多氟烷基物质的毒代动力学模型

膳食摄取在鱼类全氟烷基和多氟烷基物质 （PFAS） 的生物积累中起着重要作用。然而，现有的 PFAS 膳食摄取的毒代动力学模型是有限的。在这项研究中，成年斑马鱼暴露于具有不同结构的饮食传播 PFAS 3 天，然后进行 12 天的净化。通过毒代动力学模型监测和预测斑马鱼中的 PFAS 水平。实验结果表明，间歇性喂养导致 PFAS 水平在喂养间隔期间达到峰值。考虑间歇性喂养的双室模型可以准确描述 PFAS 的膳食摄取动力学，并提供对同化效率的稳健估计。PFAS 水平波动的程度由全身的消除速率常数决定。随后，开发了一种考虑间歇性膳食摄取的基于生理学的毒代动力学 （PBTK） 模型，以预测斑马鱼体内 PFAS 的内部负荷和组织分布。将间歇进料纳入 PBTK 模型显著提高了模型性能，并为暴露期间的大多数实验测量提供了 2 倍以内的 PFAS 水平估计值。本研究强调了间歇性饮食摄入对鱼类 PFAS 体内负荷的显着影响，并倡导将其整合到毒代动力学模型框架中。