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. 2020 May;94(5):1601-1612. doi: 10.1007/s00204-020-02705-6. Epub 2020 Mar 13.
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been used in various industrial applications for many years. Long-chain PFASs are ubiquitous in wildlife and are reported to have a long elimination half-life in biological systems. Moreover, significant gender difference exists in the elimination of PFASs, where less is eliminated in male than in female. Recently, PFASs manufacturers and agencies have tried to replace the use of long-chain PFASs with short-chain PFASs, since they are expected to exhibit less bioaccumulation potential. Nevertheless, the potential risk and the pharmacokinetic (PK) characteristics of the short-chain PFASs still remain unknown. This study aims to fill the knowledge gap on short-chain PFASs, perfluoropentanoic acid (PFPeA), in terms of its PK properties using non-linear mixed-effect modeling and to explore gender differences in rats. Animal studies were carried out following oral or intravenous administration of PFPeA in male and female rats at a dose of 0.5-10 mg/kg. Plasma, urine, feces and nine tissues were collected and analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. PK findings revealed that the clearance and the inter-compartmental clearance were 1.75 and 3.12 times higher in female rats than in male rats, respectively. According to the result, PFPeA is eliminated more rapidly in female rats than in male rats. Also, the tissue distribution study confirmed that distribution characteristics exhibited gender difference. This study provides scientific evidence for conducting further investigation into short-chain PFASs, biomonitoring plans and decision making regarding human health risk assessment.
全氟烷基和多氟烷基物质（PFASs）多年来在各种工业应用中得到广泛应用。长链 PFASs 在野生动物中普遍存在，据报道，它们在生物系统中的消除半衰期很长。此外，PFASs 的消除存在显著的性别差异，男性消除的量比女性少。最近，PFASs 的制造商和机构试图用短链 PFASs 替代长链 PFASs 的使用，因为它们预计具有较低的生物累积潜力。然而，短链 PFASs 的潜在风险和药代动力学（PK）特征仍然未知。本研究旨在使用非线性混合效应建模填补有关短链 PFASs（全氟戊酸，PFPeA）的知识空白，研究其 PK 特性，并探索大鼠中的性别差异。在雄性和雌性大鼠中，以 0.5-10mg/kg 的剂量经口服或静脉内给予 PFPeA 后进行动物研究。使用超高效液相色谱-串联质谱法收集和分析血浆、尿液、粪便和 9 种组织。PK 研究结果表明，雌性大鼠的清除率和隔室间清除率分别比雄性大鼠高 1.75 倍和 3.12 倍。根据结果，PFPeA 在雌性大鼠中的消除速度比在雄性大鼠中更快。此外，组织分布研究证实了性别差异的分布特征。本研究为进一步研究短链 PFASs、生物监测计划以及人类健康风险评估决策提供了科学依据。
