Key Takeaways & Executive Findings
- •• • PFAS bind to human serum albumin with high affinity, facilitating transport across the blood-brain and placental barriers, leading to accumulation in protein-rich organs such as liver and kidneys, with PFOS water half-life ~9 years. • • PFAS concentrations in economically developed Chinese regions reach 718 ng/L in the Bohai Rim, 586.2 ng/L in the Yangtze River Delta, and 346.72 ng/L in the Pearl River Delta, indicating significant environmental exposure. • • Binding affinity of PFAS to proteins is influenced by carbon chain length and functional groups, with longer chains showing higher affinity, as demonstrated in studies on steroid 5α-reductase 1 inhibition. • • PFAS can disrupt endocrine function by binding to nuclear receptors such as peroxisome proliferator-activated receptor γ (PPARγ), with oligomeric hexafluoropropylene oxide showing adipogenic activity via this pathway.
Abstract
Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic persistent organic pollutants that pose significant risks to human health. Owing to their high binding affinity for proteins, PFAS are ubiquitously detected in human populations worldwide. Following oral ingestion, PFAS bind to transport proteins such as human serum albumin and organic anion transporters, facilitating their distribution and accumulation in various tissues and organs, including the liver and kidneys, and enabling penetration across the blood-brain and placental barriers. This review systematically examines the migration and enrichment behaviors of PFAS in human tissues and organs mediated by multiple transport proteins, the molecular mechanisms underlying PFAS-protein interactions, and the key factors influencing these interactions. Additionally, we discuss the potential applications derived from PFAS-protein binding. By synthesizing current research findings, this review provides a theoretical foundation for future investigations into PFAS-protein interactions and outlines prospective research directions. The pervasive environmental contamination and documented health effects, including developmental retardation, endocrine disruption, obesity, and cancer, underscore the urgency of understanding PFAS toxicokinetics. Our analysis highlights the critical role of protein binding in the prolonged biological half-lives of PFAS and their tissue-specific accumulation, which are central to health risk assessment and the development of mitigation strategies.
1. Introduction
Per- and polyfluoroalkyl substances (PFAS) are anthropogenic chemicals characterized by carbon-fluorine bonds that confer exceptional stability, leading to their persistence in the environment and accumulation in living organisms. The widespread use of PFAS since the 1940s has resulted in global contamination, with production exceeding 3,000 tons between 2000 and 2017. Their resistance to degradation, exemplified by the ~9-year half-life of perfluorooctane sulfonate (PFOS) in water, poses a formidable challenge to conventional water treatment methods. Consequently, PFAS are ubiquitous in environmental matrices, with elevated concentrations reported in economically developed regions of China, such as the Bohai Rim (up to 718 ng/L), Yangtze River Delta (up to 586.2 ng/L), and Pearl River Delta (up to 346.72 ng/L). This environmental prevalence translates into continuous human exposure, primarily through dietary intake, leading to detectable levels in human populations worldwide.
The primary health concern associated with PFAS arises from their high affinity for proteins, which facilitates their transport and accumulation in protein-rich tissues and organs, including the liver and kidneys. PFAS can cross critical biological barriers, such as the blood-brain and placental barriers, thereby posing risks to the central nervous system and fetal development. Epidemiological studies have linked PFAS exposure to developmental retardation, endocrine disruption, obesity, and cancer. Understanding the molecular mechanisms of PFAS-protein interactions is essential for accurate health risk assessment and the design of effective intervention strategies. This review synthesizes current knowledge on the migration and enrichment of PFAS in human tissues, the binding mechanisms with transport proteins, and the factors influencing these interactions, thereby providing a foundation for future research and regulatory decisions.
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CHEN Qian, GU Cheng, WU Xinda (2026). Migration and Enrichment of Per- and Polyfluoroalkyl Substances (PFAS) and Their Protein Binding Behavior in Human Tissues and Organs: A Review. Environmental Chemistry. https://doi.org/10.7524/j.issn.0254-6108.2025011501
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Frequently Asked Questions
What are the primary transport proteins involved in PFAS distribution in the human body, and how do their binding affinities vary across different PFAS structures?
The primary transport proteins include human serum albumin (HSA) and organic anion transporters (OATs). Binding affinity is influenced by the carbon chain length and functional head group; longer chains and sulfonate groups generally exhibit higher affinity. For example, PFOS binds more strongly to HSA than perfluorooctanoic acid (PFOA).
How does PFAS binding to proteins affect their biological half-life and tissue accumulation?
Binding to proteins, particularly albumin, reduces the renal clearance of PFAS, leading to prolonged half-lives. For instance, PFOS has a half-life of approximately 5.4 years in humans. This results in accumulation in protein-rich tissues such as the liver and kidneys, where concentrations can be several-fold higher than in serum.
What are the key structural features of PFAS that determine their binding affinity to proteins, and how can this knowledge guide the design of safer alternatives?
Key features include chain length, degree of fluorination, and the nature of the functional group (e.g., carboxylic vs. sulfonic). Longer chains and sulfonate groups increase hydrophobicity and binding affinity. This structure-activity relationship can inform the design of shorter-chain or non-fluorinated alternatives with reduced protein binding and bioaccumulation potential.
What experimental techniques are most effective for characterizing PFAS-protein interactions, and what are their limitations?
Common techniques include fluorescence quenching, isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), and molecular docking. Fluorescence quenching provides binding constants and number of binding sites, but may be limited by inner-filter effects. ITC offers thermodynamic parameters but requires relatively high concentrations. SPR allows real-time kinetics but requires immobilization of one partner. Combining multiple methods is recommended for comprehensive understanding.
How do PFAS-protein interactions contribute to the crossing of the blood-brain barrier and placental barrier, and what are the implications for neurodevelopmental toxicity?
PFAS can bind to transport proteins expressed at these barriers, such as OATPs, facilitating their transcytosis. For example, PFOS has been detected in fetal cord blood, indicating placental transfer. This exposure during critical developmental windows may lead to neurodevelopmental deficits, as suggested by epidemiological studies linking prenatal PFAS exposure to reduced cognitive function in children.
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