Do extreme salinity fluctuations exacerbate AMPA toxicity? Experimental evidence and hazard characterization in Mediterranean mussels

Climate change may exacerbate extreme weather events, leading to severe salinity fluctuations in coastal waters and enhancing the mobility of land-based pollutants such as aminomethylphosphonic acid (AMPA), the main breakdown product of glyphosate. Although the individual effects of salinity stress and AMPA are increasingly characterized, their combined impact on marine organisms is still poorly investigated.This study aimed to assess, for the first time, the effects of different salinity scenarios (35, 25, 15) on the toxicity of environmentally realistic concentrations of AMPA (0.5 μg/L) in Mytilus galloprovincialis. A wide panel of cholinergic functions, immunological responses, antioxidant defences and oxidative damage, peroxisomal proliferation, and energy metabolism was evaluated after 21 days of exposure, and the results elaborated using weighted criteria to provide hazard classification based on magnitude and toxicological relevance of observed effects. Results indicated that AMPA exposure significantly influenced cholinergic responses, detoxification mechanisms and antioxidant defences. Beyond the direct effects, salinity modulated AMPA toxicity, either exacerbating or counteracting specific effects on immune function, oxidative balance, and metabolic homeostasis, with tissue-specific patterns. The Weight of Evidence approach assigned a higher hazard classification to combined stressor scenarios, further corroborating the importance of exploring interactive toxicological effects. Overall, this work provided a novel integrative toxicological profiling of AMPA under climate change-driven salinity stress, emphasizing the need to consider the interactions between multiple co-occurring stressors in environmental risk assessment frameworks.