Fluopyram induces behavioural, hepatotoxic and metabolic alterations in fish at environmentally relevant...

Succinate dehydrogenase inhibitor (SDHI) fungicides are increasingly used and detected in surface waters, raising concerns for non-target aquatic organisms because they may disrupt mitochondrial metabolism. As mitochondrial structure and function are highly conserved in fungi and vertebrates, exposure to SDHIs could affect fish health; however, empirical data remain limited. Here, we assessed the short-term (4 days) and subchronic (21 days) effects of fluopyram, a commonly used SDHI, on adult goldfish (Carassius auratus) exposed to environmentally relevant concentrations (1 and 10 µg.L^-1). To this end, we combined behavioural endpoints, blood indicators of stress and immune status, hepatic detoxification capacity (GST activity), liver histopathology, and targeted profiling of hepatic lipids and polar metabolites. Behavioural responses were among the most sensitive endpoints, with increased feeding latency, locomotor activity and social interactions mainly observed at 1 µg.L^-1. Liver histology revealed clear hepatotoxicity, with progressive lesions (including necrosis/lysis, fibrosis and vacuolisation) increasing over time. While total hepatic lipid content was not markedly changed, lipidomic analysis indicated substantial remodelling, notably increased triacylglycerols and cholesteryl esters after 21 days. Some responses appeared to be more marked in one sex than the other, with early alterations observed mainly in males and delayed metabolic changes at 21 days more evident in females, including increased unsaturated fatty acids and shifts in central carbon metabolism. These patterns are compatible with a possible limitation of mitochondrial energy metabolism and compensatory glycolytic reorientation. Overall, this study shows that fluopyram affects fish health at concentrations close to those reported in freshwaters. This confirms the need to monitor SDHI fungicide impacts on wildlife.