Per- and polyfluoroalkyl substances (PFAS) are ultra‑persistent anthropogenic chemicals whose strength of the C–F bond facilitates long-range atmospheric transport and trophic transfer. Applying a One Health framework, we bridged field surveys, mesocosm food‑web simulations and structure–function analyses to characterize ecological and neurotoxic liabilities of both legacy and emerging PFAS congeners.

Field sampling at a brackish wetland in southern Sweden detected PFOS and PFOA across four trophic levels (n = 158), with trophic magnification factors exceeding unity, confirming biomagnification in invertebrate food webs. Controlled mesocosm experiments replicating simplified terrestrial food chains corroborated these trends and revealed significant reproductive impairments in Eisenia fetida, including a 30 % reduction in cocoon output after 30 d (Welch’s ANOVA, p < 0.05). In laboratory assays, earthworms exposed to environmentally relevant PFAS concentrations exhibited pronounced GABA depletion under GenX and PFOA, elevated acetylcholinesterase activity with GenX and MOBA, and modulation of serotonin and tryptophan. Escape‑latency tests further demonstrated delayed responses in GenX‑treated and soil‑transplanted worms, indicating compromised defensive behaviour.

At the molecular scale, 400‑ns atomistic simulations and patch‑clamp recordings in SH‑SY5Y neurons demonstrated stable lodging of PFOA and PFOS within the α1β3γ2 GABAA receptor pore, yielding complete reversible suppression of chloride currents for PFOS and ~50 % inhibition for PFOA at physiologically relevant concentrations.

This multiscale evidence—from receptor blockade and neurotransmitter imbalance to reproductive deficits and trophic amplification—underscores the urgent need for advanced biomonitoring, integrative risk assessment and scalable remediation strategies to mitigate the planetary PFAS burden.