College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea.
College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-Gu, Gwangju, 61186, Republic of Korea.
Arch Toxicol. 2019 Feb;93(2):311-330. doi: 10.1007/s00204-018-2365-y. Epub 2018 Nov 27.
Perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), which are classified as perfluoroalkyl and polyfluoroalkyl substances (PFASs), have been widely used in industrial applications as a surface protectant. PFASs have been detected in wildlife and in humans around the globe. The purposes of this study are to develop and validate a physiologically based pharmacokinetic (PBPK) model for detecting PFNA and PFDA in male and female rats, and to apply the model to a human health risk assessment regarding the sex difference. A PBPK model of PFNA and PFDA was established based on an in vivo study in male and female rats. Analytes in biological samples (plasma, nine tissues, urine, and feces) were determined by ultra-liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS) method. PFNA and PFDA showed a gender differences in the elimination half-life and volume of distribution. The tissue-plasma partition coefficients were the highest in the liver in both male and female rats. The predicted rat plasma and urine concentrations simulated and fitted were in good agreement with the observed values. The PBPK models of PFNA and PFDA in male and female rats were then extrapolated to a human PBPK model based on human physiological parameters. The external doses were calculated at 3.35 ng/kg/day (male) and 17.0 ng/kg/day (female) for PFNA and 0.530 ng/kg/day (male) and 0.661 ng/kg/day (female) for PFDA. Human risk assessment was estimated using Korean biomonitoring values considering the gender differences. This study provides valuable insight into human health risk assessment regarding PFNA and PFDA exposure.
全氟壬酸 (PFNA) 和全氟癸酸 (PFDA) 属于全氟烷基和多氟烷基物质 (PFAS)，已广泛应用于工业领域作为表面保护剂。PFAS 已在全球野生动物和人类中被检测到。本研究旨在开发和验证一种用于检测雄性和雌性大鼠中 PFNA 和 PFDA 的基于生理的药代动力学 (PBPK) 模型，并将该模型应用于人类健康风险评估中的性别差异。 基于雄性和雌性大鼠体内研究，建立了 PFNA 和 PFDA 的 PBPK 模型。通过超高效液相色谱串联质谱 (UPLC-MS/MS) 法测定生物样本（血浆、九种组织、尿液和粪便）中的分析物。PFNA 和 PFDA 在消除半衰期和分布容积方面表现出性别差异。在雄性和雌性大鼠中，组织-血浆分配系数在肝脏中最高。预测的大鼠血浆和尿液浓度与观察值模拟和拟合良好。然后，根据人体生理参数，将雄性和雌性大鼠的 PFNA 和 PFDA 的 PBPK 模型外推到人体 PBPK 模型。PFNA 的外剂量计算为 3.35ng/kg/天（雄性）和 17.0ng/kg/天（雌性），PFDA 的外剂量计算为 0.530ng/kg/天（雄性）和 0.661ng/kg/天（雌性）。考虑到性别差异，使用韩国生物监测值对人体风险评估进行了估计。本研究为评估 PFNA 和 PFDA 暴露对人类健康的风险提供了有价值的见解。
