Evaluation of the developmental toxicity of 2,7-dibromocarbazole to zebrafish based on transcriptomics assay.

Graphical abstract Highlights • Acute embryotoxicity: 2,7-DBCZ >> 3,6-DBCZ ≅ 3,6-DCCZ. • Zebrafish embryos exposed to 2,7-DBCZ develop significant malformation, especially pericardial edema. • Transcriptomics assay shows that 2,7-DBCZ induced developmental toxicity in zebrafish by AhR activation. Abstract Polyhalogenated carbazoles (PHCZs), which have the similar structure of dioxin, have been reported ubiquitous in the environments and drawn wide concerns. However, their potential ecological and health risks are still poorly understood. Here, wildtype zebrafish embryos were used to evaluate the environmental risks of 2,7-dibromocarbazole (2,7-DBCZ), 3,6-dibromocarbazole (3,6-DBCZ), and 3,6-dichlorocarbazole (3,6-DCCZ). 2,7-DBCZ was the most toxic compound with the 96-h LC 50 value of 581.8 ± 29.3 μg·L−1 and the EC 50 value of 201.5 ± 6.5 μg·L−1 for pericardial edema. The teratogenic effects of 2,7-DBCZ were tested using transgenic zebrafish larvae. The transcriptomic analysis revealed that 90 genes in zebrafish expressed differently after exposure to 2,7-DBCZ, and many pathways were related to aryl hydrocarbon receptor (AhR) activation. The qRT-PCR also showed that expression levels of AhR1 and CYP1 A in zebrafish were significantly up-regulated after exposure to 2,7-DBCZ. In conclusion, 2,7-DBCZ exhibited more potent toxicity and cardiac teratogenic effects, and presented developmental toxicity partially consistent with AhR activation. Our results will be of great help to the risk assessment and regulation-making of PHCZs. Meanwhile, further studies should be promoted to illustrate the potential mechanism between PHCZs and AhR in the near future. [ABSTRACT FROM AUTHOR]