Developmental and Neurobehavioral Toxicity of Etomidate in Zebrafish Across Life Stages

Etomidate (ETO), a widely used intravenous anesthetic, is increasingly recognized as an emerging environmental contaminant due to its persistence in aquatic systems and potential ecotoxicological effects. This study examined the developmental and neurobehavioral effects of ETO in zebrafish across life stages, encompassing environmentally relevant (0.001-0.1 mg/L) and higher concentrations. In zebrafish embryos, ETO exposure significantly delayed hatching, increased mortality, and induced morphological abnormalities, including pericardial edema, reduced body length, impaired swim bladder inflation, and reduced eye size. Photomotor response assays showed that larval locomotor activity was suppressed at 0.1 mg/L and above. In adult zebrafish, exposure to ETO at 0.001-0.1 mg/L elicited neurobehavioral alterations, such as increased anxiolytic-like behavior, enhanced social preference, and disrupted shoaling cohesion. RT-qPCR analysis revealed significant dysregulation of GABAA and dopaminergic pathway genes, suggesting that ETO disrupts associated neurochemical signaling in zebrafish. These findings demonstrate that environmentally realistic levels of ETO induce developmental toxicity and neurobehavioral disturbances in aquatic vertebrates, highlighting the need for ecological risk assessment and regulatory attention for pharmaceutical anesthetics.