PFAS Depuration in Humans: Toxicokinetics, Elimination Strategies, and Clinical Challenges
https://doi.org/1234
Keywords:
PFAS Toxicokinetics Bioaccumulation Elimination Biological half-lives Recirculation Bile acid sequestrants Cholestyramine Plasmapheresis Dietary FiberAbstract:
Per- and polyfluoroalkyl substances (PFAS) are a class of persistent synthetic chemicals that bioaccumulate in humans, leading to widespread exposure and detectable body burdens in nearly all individuals. The remarkable persistence of PFAS is driven by their unique toxicokinetic properties, such as metabolic inertness and highly efficient renal and enterohepatic recirculation, resulting in biological half-lives spanning several years. Mounting epidemiological evidence links this chronic internal exposure to various adverse health outcomes, including endocrine disruption, cardiovascular disease, immunotoxicity, and impacts on male reproductive health. While source reduction is crucial, there is a critical need for effective strategies to accelerate the elimination of these chemicals in individuals with high body burdens. This review synthesizes the current research on human PFAS depuration, detailing the toxicokinetic mechanisms that govern their persistence, including the roles of serum protein binding and transporter-mediated recirculation. Interventions with human clinical data are critically evaluated, focusing on pharmaceutical approaches that interrupt recirculation pathways, such as bile acid sequestrants like cholestyramine, which has shown significant efficacy in a recent clinical trial. Emerging lifestyle-based strategies, such as dietary fiber supplementation and physical activity, are also discussed for their potential to enhance elimination and mitigate the adverse metabolic effects associated with PFAS exposure. However, the most significant research gap identified is the need for long-term clinical trials that definitively link a reduction in the PFAS body burden to tangible improvements in health outcomes, which is essential for validating and implementing future therapeutic interventions. Ultimately, integrating these depuration strategies with robust public health measures aimed at reducing ongoing environmental exposure will be crucial to meaningfully address the global health challenge posed by PFAS.
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