Polyhalogenated carbazoles (PHCZs) induce cardiotoxicity and behavioral changes in zebrafish at early developmental stages

Polyhalogenated carbazoles (PHCZs) are widely present in the environment, and their health risks are of increasing concern. Available studies primarily confirm their dioxin-like toxicity mechanism based on biomarkers, such as aryl hydrocarbon receptor (AHR) and CYP1A1, while few studies have investigated their actual toxic effects at the level of individual organisms. In the present study, the developmental toxicity of two typical PHCZs with a high detection rate and high concentration in the environment (3,6-dichlorocarbazol (3,6-DCCZ) and 3,6-dibromocarbazole (3,6-DBCZ)) was investigated based on a fish embryo acute toxicity test (FET, zebrafish) and transcriptomics analysis. The 96 h LC50 values of 3,6-DCCZ and 3,6-DBCZ were 0.636 mg/L and 1.167 mg/L, respectively. Both tested PHCZs reduced the zebrafish heart rate and blocked heart looping at concentrations of 0.5 mg/L or higher. The swimming/escaping behavior of zebrafish larvae was more vulnerable to 3,6-DBCZ than 3,6-DCCZ. Transcriptomics assays showed that multiple pathways linked to organ development, immunization, metabolism and protein synthesis were disturbed in PHCZ-exposed fish, which might be the internal mechanism of the adverse effects. The present study provides evidence that PHCZs cause cardiac developmental toxicity and behavioral changes and improves our understanding of their health risks.