Oxidative stress-mediated cardio- and neurotoxicity of 2-ethylhexanol in Daphnia magna.

2-Ethylhexanol, a common component of plasticizers and solvents, is increasingly detected in aquatic environments and may pose ecological risks. This study evaluated the sublethal effects of 2-ethylhexanol on Daphnia magna by integrating physiological, biochemical, behavioral, and transcriptional markers related to cardiac function and nervous system activity. D. magna were exposed to 0.69, 1.75, 6.25, and 19.23 mg/L 2-ethylhexanol for 48 h, and endpoints included cardiac and thoracic limb activity, swimming behavior, neurochemical markers [acetylcholinesterase (AChE), dopamine (DA)], oxidative stress indicators [catalase (CAT), total nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)], and transcription of cardio- and neurotoxicity-related genes. Exposure caused dose-dependent inhibition of cardiac rhythm and thoracic limb movement, together with neurobehavioral alterations, including reduced body contact time and increased turn angle, accompanied by decreased DA levels and suppressed AChE activity. Dysregulation of cardiomyopathy-associated genes (sgcd, adcy5_1, gclm, and tpm3) and neurotoxicity-related genes (drd2, slc6a3, and slc6a6) indicated mechanistic links to oxidative stress-mediated cardio-neurotoxicity. Oxidative stress responses were characterized by increased CAT, NO, SOD, and GSH-Px activity, with SOD consistently upregulated at all concentrations. Collectively, these physiological, biochemical, behavioral, and molecular alterations demonstrate that 2-ethylhexanol induces cardiotoxicity and neurobehavioral impairment in D. magna, likely via oxidative stress, with potential to disrupt predator-prey interactions in aquatic ecosystems. These findings support the use of D. magna as a sensitive model for sub-organismal toxicity and the need to re-evaluate environmental safety thresholds for 2-ethylhexanol and similar plasticizer-related contaminants.