Abstract：
PER: and polyfluoroalkyl substances (PFASs) have been associated with increased blood lipids in humans. Perfluorooctanoic acid (PFOA) has been also linked with elevated alanine transferase (ALT) serum levels in humans, and in rodents the liver is a main target organ for many PFASs. With the focus on New Approach Methodologies, the chronic oral equivalent effect doses were calculated for PFOA, PFNA (perfluorononanoic acid), PFHxS (perfluorohexanesulfonic acid) and PFOS (perfluorooctane sulfonic acid) based on in vitro effects measured in the HepaRG cell line. Selected in vitro readouts were considered biomarkers for lipid disturbances and hepatotoxicity. Concentration-response data obtained from HepaRG cells on triglyceride (TG) accumulation and expression changes of 12 selected genes (some involved in cholesterol homeostasis) were converted into corresponding human dose-response data, using physiologically based kinetic (PBK) model-facilitated reverse dosimetry. Next to this, the biokinetics of the chemicals were studied in the cell system. The current European dietary PFASs exposure overlaps with the calculated oral equivalent effect doses, indicating that the latter may lead to interference with hepatic gene expression and lipid metabolism. These findings illustrate an in vitro-in silico methodology, which can be applied for more PFASs, to select those that should be prioritized for further hazard characterization.
摘要：
PER：和多氟烷基物质（PFAS）与人类血脂增加有关。全氟辛酸（PFOA）也与人类丙氨酸转移酶（ALT）血清水平升高有关，在啮齿动物中，肝脏是许多PFAS的主要靶器官。专注于新方法方法，计算PFOA的慢性口服等效效应剂量，PFNA（全氟壬酸），基于在HepaRG细胞系中测量的体外效应的PFHxS(全氟己烷磺酸)和PFOS(全氟辛烷磺酸)。选择的体外读数被认为是脂质紊乱和肝毒性的生物标志物。从HepaRG细胞获得的关于甘油三酯(TG)积累和12个选定基因(一些参与胆固醇稳态)的表达变化的浓度-反应数据被转换成相应的人剂量-反应数据,使用基于生理学的动力学（PBK）模型促进的反向剂量测定法。在这个旁边,在细胞系统中研究了化学物质的生物动力学。当前的欧洲膳食PFAS暴露与计算的口服等效效应剂量重叠，表明后者可能导致肝脏基因表达和脂质代谢的干扰。这些发现说明了一种体外计算机方法，可以应用于更多的PFAS，选择应优先进行进一步危险表征的那些。
