An overview of the impact of PFAS on animals, humans, and the environment using a One Health approach.

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals characterized by a fluorinated carbon chain that confers unique physicochemical properties. Widely used in industrial and consumer products, including textiles, food packaging, and firefighting foams, PFAS are highly persistent in the environment, earning them the designation of "forever chemicals." Their stability contributes to their widespread diffusion across different environmental compartments (water, soil, air) and multiple exposure pathways (e.g., diet). These lead to PFAS bioaccumulation and biomagnification, which poses a substantial threat to both ecosystems and human health. Exposure to PFAS has been associated with a range of adverse health effects, including liver damage, thyroid disease, immunotoxicity, reproductive issues, and various cancers in both humans and animals. While regulatory efforts have led to the phase-out of long-chain PFAS such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), emerging research suggest that their short-chain replacements may also raise health concerns. This review applies a One Health framework to explore the interconnected impacts of these contaminants on human, animal, and environmental health. Furthermore, it highlights knowledge gaps that hinder comprehensive risk assessment and management, emphasizing the need for a globally coordinated, multidisciplinary approach to address the multifaceted challenges posed by PFAS.