Developmental and multi-organ toxicity of fludioxonil in zebrafish through apoptosis, oxidative stress, and...

Fludioxonil, a widely used phenylpyrrole-class fungicide, has drawn growing concerns owing to its persistent detection in the environment and its potential for diverse toxic effects. This study investigated the developmental toxic effects of fludioxonil using zebrafish (Danio rerio) as a model organism. Exposure to fludioxonil resulted in reduced survival rates and induced multi-organ toxicity. Fludioxonil-induced organ-specific toxicity was assessed using transgenic fluorescent reporter lines, including fli1a:EGFP, huC:EGFP, gad1b:EGFP, fabp10a:dsRed, and elastase:EGFP. Notably, cardiovascular development was substantially impaired, while neurotoxic effects manifested as disrupted neural development and altered brain structures. Metabolic organs, including the liver and pancreas, exhibited developmental abnormalities and functional decline. Mechanistic analyses revealed increased DNA fragmentation, which is indicative of apoptosis, and elevated production of reactive oxygen species, suggesting oxidative stress and mitochondrial dysfunction. These results suggest that fludioxonil disrupts normal development through common molecular and cellular pathways involving oxidative damage and compromised energy metabolism. We provide critical insights into the toxicological effects of fludioxonil during early embryogenesis, revealing the potential risks posed by this pesticide to non-target aquatic species. This study underscores the importance of comprehensively investigating fludioxonil-induced developmental toxicity and elucidating the underlying mechanistic pathways to guide environmental risk assessments and regulatory decisions.