Abstract

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.

中文翻译：

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使用非线性混合效应模型在大鼠中全氟戊酸药代动力学的性别差异。

摘要

全氟烷基和多氟烷基物质（PFAS）已在各种工业应用中使用了很多年。长链PFAS在野生生物中无处不在，据报道在生物系统中具有长的消除半衰期。此外，消除PFAS存在明显的性别差异，男性消除的因素少于女性。最近，PFAS制造商和代理机构已尝试用短链PFAS代替长链PFAS，因为它们的生物蓄积潜力较小。尽管如此，短链PFAS的潜在风险和药代动力学（PK）特征仍然未知。这项研究旨在填补短链PFAS，全氟戊酸（PFPeA），使用非线性混合效应模型对其PK特性进行研究，并探讨大鼠的性别差异。在雄性和雌性大鼠口服或静脉注射PFPeA后，以0.5-10 mg / kg的剂量进行动物研究。收集血浆，尿液，粪便和九个组织，并使用超高效液相色谱-串联质谱法进行分析。PK结果表明，雌性大鼠的清除率和室间清除率分别比雄性大鼠高1.75倍和3.12倍。根据结果​​，雌性大鼠比雄性大鼠更快地消除了PFPeA。另外，组织分布研究证实分布特征表现出性别差异。这项研究为进一步研究短链PFAS提供了科学依据，