2,6-di-tert-butylphenol tert-butylphenol (2,6-DTBP) has been used extensively in plastics, rubber and polymer phenolic antioxidants. It is discharged into the aquatic environment through industrial waste. However, the toxicity assessment of 2,6-DTBP is insufficient. Here, zebrafish embryos were used as an animal model to investigate the toxicological effects of 2,6-DTBP. The results showed that 2,6-DTBP induced mitochondrial dysfunction and reactive oxygen species accumulation, which caused apoptosis, and further led to developmental toxicity of zebrafish embryos, such as delayed incubation, reduced survival rate, and increased malformation rate and heart rate. 2,6-DTBP can also cause morphological changes in the zebrafish endothelial cell (zEC) nucleus, inhibit zEC migration, trigger abnormal angiogenesis and zEC sprouting angiogenesis, and ultimately affect vascular development. In addition, 2,6-DTBP interfered with the endogenous antioxidant system, causing changes in activities of superoxide dismutase, catalase, and glutathione S-transferase and contents of malondialdehyde and glutathione. Transcriptome sequencing showed that 2,6-DTBP altered the mRNA levels of genes associated with vascular development, oxidative stress, apoptosis, extracellular matrix components and receptors. Integrative biomarker response assessment found that 12 mu M 2,6-DTBP had the highest toxicity. These results indicated that 2,6-DTBP induced apoptosis through oxidative stress, leading to toxicity of zebrafish embryo development. This study contributes to understanding the effects of environmental 2,6-DTBP exposure on early development of aquatic organisms and draws public attention to the health risks posed by chemicals in aquatic organisms.
