Hormetic effects of per- and polyfluoroalkyl substances on ecologically relevant animal models: Generality, quantitative features, and risk assessment implications.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants of global concern, yet substantial uncertainty remains regarding their health and ecological risks, particularly at low exposure levels. This paper provides the first extensive evaluation of PFAS-induced hormetic dose responses across a wide range of ecological models, from bacteria to vertebrates, and, where available, examines the underlying mechanisms. Hormesis, characterized by low-dose stimulation and high-dose inhibition, is shown to be a common and evolutionarily conserved response to PFAS exposure. Evidence across diverse taxa-including zebrafish, invertebrates, insects, amphibians, and microbial systems-demonstrates consistent biphasic dose-response relationships affecting endpoints such as locomotion, immune function, reproduction, growth, and survival. Quantitative features of these responses generally align with established hormetic patterns, with stimulatory effects often occurring well below toxic thresholds. Mechanistically, PFAS-induced hormesis appears to involve adaptive processes such as modulation of oxidative stress, immune activation, and metabolic reprogramming. The findings highlight the generality of hormesis across biological systems and suggest that low-dose PFAS exposures may elicit adaptive or beneficial responses under certain conditions. These results challenge traditional toxicological assumptions and underscore the importance of incorporating hormetic dose-response models into ecological risk assessment frameworks.