Bromoacetic acid and dibromoacetic acid induce cardiotoxicity in larval zebrafish by triggering oxidative stress.

Disinfection by-products are widespread contaminants formed during water disinfection processes, with bromoacetic acids (BAAs), including bromoacetic acid (BAA) and dibromoacetic acid (DBAA), frequently detected in swimming pools, spas, and tap water. Although their environmental occurrence is well documented, the in vivo organ-specific toxicity of BAAs remains poorly understood. In this study, zebrafish (Danio rerio) were employed to investigate the developmental and cardiotoxic effects of BAA and DBAA, individually and in combination. Exposure to BAA or combined BAA/DBAA significantly increased mortality and reduced hatching rates, whereas DBAA alone showed no significant effect on hatching. Both compounds induced morphological abnormalities, including reduced body length, swim bladder defects, and pericardial edema. Cardiac assessments revealed enlarged pericardial areas, decreased heart rates, and downregulation of key cardiac developmental genes. BAAs also elevated reactive oxygen species (ROS) levels in the heart, upregulated ROS-generating genes, and suppressed antioxidant genes. Furthermore, BAAs reduced cardiomyocyte proliferation, increased γH2AX-positive cells, and upregulated apoptosis-related genes, indicating DNA damage and apoptosis. Co-treatment with the antioxidant N-acetylcysteine mitigated pericardial edema and reduced γH2AX-positive cells, confirming a central role of oxidative stress in BAAs-induced cardiotoxicity. These findings demonstrate that BAA and DBAA impair zebrafish heart development through oxidative stress-mediated disruption of cell proliferation and promotion of apoptosis. This study highlights the need for further evaluation of BAA and DBAA toxicity to better understand their potential health risks in humans.