Structure-related differences in plasma protein binding of per- and polyfluoroalkyl substances in mice and humans

IF 4.6 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2025-12-01 Epub Date: 2025-11-26 DOI:10.1016/j.etap.2025.104879

Chloé ML. Argoul , Pierre-Louis Toutain , Sarah Berard , Nicole Picard-Hagen , Véronique Gayrard , Marlène Z. Lacroix

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Abstract

Understanding interspecies and structure-based differences in the toxicokinetics of perfluoroalkyl substances (PFAS) is important to explain their persistence and improve health risk assessment. Since renal clearance is the main elimination pathway, this study measured the free (protein-unbound) fraction (f_u) of PFAS in human and mouse plasma using the Dianorm^R system, selected for its robustness and rapid equilibrium. Sixteen PFAS were tested, including perfluoroalkyl carboxylic acids (PFCA), sulfonic acids (PFSA), and ether derivatives (PFECA). Mean f_u values ranged from 0.21 % (PFOS) to 50 % (PFPeA) in mice and from 0.02 % (PFHpS) to 8.5 % (PFPeA) in humans. Interspecies differences were most pronounced for short-chain PFAS and PFECA, but not observed for longer chains. A U-shaped relationship between f_u and molecular weight (MW) was found, with the lowest values near 400–500 g/mol. These results highlight plasma protein binding as a key determinant of PFAS persistence and provide predictive models linking f_u to MW.

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小鼠和人血浆蛋白与全氟烷基和多氟烷基物质结合的结构相关差异

了解全氟烷基物质（PFAS）毒性动力学的种间差异和基于结构的差异对于解释其持久性和改进健康风险评估具有重要意义。由于肾脏清除是主要的清除途径，本研究使用DianormR系统测量了人类和小鼠血浆中PFAS的游离（蛋白未结合）部分（fu），该系统因其稳健性和快速平衡而被选择。测试了16种PFAS，包括全氟烷基羧酸（PFCA）、磺酸（PFSA）和醚衍生物（PFECA）。小鼠的平均fu值从0.21 % （PFOS）到50 % （PFPeA）不等，人类的平均fu值从0.02 % （PFHpS）到8.5 % （PFPeA）不等。短链PFAS和PFECA的种间差异最明显，而长链PFAS和PFECA的种间差异不明显。fu与分子量（MW）呈u型关系，最小值在400 ~ 500 g/mol附近。这些结果强调血浆蛋白结合是PFAS持久性的关键决定因素，并提供了将fu与MW联系起来的预测模型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.