Developmental toxicity of fenbuconazole in zebrafish: Effects on mitochondrial respiration and locomotor behavior

Triazole fungicides are used to control the disease of cereal crops but may also cause adverse effects on nontarget organisms. There is a lack of toxicity data for some triazoles such as fenbuconazole in aquatic organisms. This research was conducted to evaluate the toxicity of fenbuconazole at environmentally relevant concentrations with attention on the mitochondria, antioxidant system, and locomotor activity in zebrafish. Zebrafish were exposed to one concentration of 5, 50, 200 or 500 ng/L fenbuconazole for 96 h. There was no effect on survival nor percentage of fish hatched, but exposure to 200 and 500 ng/L fenbuconazole resulted in malformation and hypoactivity in zebrafish. Oxygen consumption rates (OCR) of embryos were measured to determine if the fungicide impaired mitochondrial respiration. Exposure to 500 ng/L fenbuconazole reduced basal OCR and oligomycin-induced ATP linked respiration in exposed fish. Fenbuconazole reduced mitochondrial membrane potential and reduced the activities of mitochondrial Complex II and III. Transcript levels of both sdhc and cyc1, each related to Complex II and III, were also altered in expression by fenbuconazole exposure, consistent with mitochondrial dysfunction in embryos. Fenbuconazole activated the antioxidant system, based upon both transcriptional and enzymatic data in zebrafish. Consistent with mitochondrial impairment, molecular docking confirmed a strong binding capacity of the fungicide at the Q(i) site of Complex III, revealing this complex is susceptible to fenbuconazole. This study reveals potential toxicity pathways related to fenbuconazole exposure in aquatic organisms; such data can improve risk assessments for triazole fungicides.