Comparative Toxicity of Perfluorooctanoic Acid and Perfluorobutanoic Acid on Microcystis aeruginosa : Growth, Cellular Mechanisms, and Metabolic Response

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants with potential ecological toxicity. Short-chain PFAS, such as perfluorobutanoic acid (PFBA), are often considered safer alternatives to long-chain compounds like perfluorooctanoic acid (PFOA), yet their effects on freshwater microorganisms remain poorly understood. This study systematically compared the toxic effects of PFBA and PFOA on Microcystis aeruginosa, integrating physiological assessments and untargeted metabolomics. At lower concentrations (0.01–1 mg/L), both PFAS had negligible effects, whereas higher concentrations (10–50 mg/L) significantly inhibited algal growth, reduced chlorophyll a and carotenoid contents, and induced oxidative stress. PFBA exhibited stronger acute toxicity, with a 72-h EC50 of 24.83 mg/L versus 43.55 mg/L for PFOA. Metabolomic profiling revealed that both PFAS disrupted key metabolic pathways, including energy production, carbohydrate metabolism, and nucleotide metabolism, impairing cellular homeostasis and physiological function. Notably, PFOA-exposed cells showed certain adaptive metabolic responses, such as upregulation of pyrimidine metabolism and glucuronidation-related detoxification pathways, whereas PFBA induced broader and more severe metabolic perturbations, including markers of lipid peroxidation. These findings provide new insights into the effects of PFBA and PFOA on algae and the environmental risk assessment of PFAS.