Integrated Approaches to Testing and Assessment of Per and Poly-FluoroAlkyl Substances (PFAS)

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants characterized by extreme persistence, bioaccumulative potential, and multiple toxic effects. This doctoral research, framed within the One Health paradigm, adopts an Integrated Approach to Testing and Assessment (IATA) to evaluate the biological impact of PFAS at different levels of biological organization. A first experimental phase used the model species Eisenia fetida to investigate behavioral and biochemical changes following exposure to several PFAS, including legacy and short-chain compounds. The results revealed significant alterations in oxidative stress markers, enzymatic activity (e.g., catalase, superoxide dismutase, acetylcholinesterase), and neuromuscular behavior. Neurotoxic effects were further assessed using human S1 neuroblastoma cells, through patch-clamp recordings of GABA-evoked currents. PFOS and PFOA induced a marked inhibition of GABA_A receptor activity, suggesting a potential mechanism of synaptic disruption. Additionally, proteomic analyses conducted on human peripheral blood mononuclear cells (PBMCs) exposed to PFOS revealed modulation of proteins involved in immune response and apoptosis, along with altered cytokine production. The integration of data from ecotoxicological, neurological, and immunological models demonstrates that PFAS can interfere with key physiological systems even at low concentrations. This work highlights the importance of multidisciplinary strategies for PFAS risk assessment and supports the implementation of science-based regulatory measures in a One Health context.