Developmental Toxicity of Tetrabromobisphenol A Bis(allyl ether) in Zebrafish: Redox Disturbance and Osteoclast-Associated Skeletal Responses

Tetrabromobisphenol A bis(allyl ether) (TBBPA-BAE) is an emerging aquatic contaminant, yet its developmental toxicity, particularly its stage-dependent skeletal effects, remains poorly understood. Zebrafish embryos and larvae were continuously exposed to nominal concentrations of 0.2, 2, 20, or 200 µg/L TBBPA-BAE (BAE0.2, BAE2, BAE20, and BAE200) through 14 days post-fertilization (dpf), with the lowest concentration approximating the upper end of reported environmental concentrations. Exposure transiently delayed hatching and altered heart rate and locomotion. At 5 dpf, H2O2 increased at all concentrations, whereas superoxide-scavenging capacity, catalase, and total superoxide dismutase showed distinct concentration-dependent responses, indicating disrupted redox homeostasis rather than uniform antioxidant activation. Selective craniofacial cartilage changes were also observed. At 14 dpf, craniofacial mineralization changed non-monotonically, increasing in BAE2 and BAE20 but decreasing in BAE200. Increased cranial TRAP staining together with osteoclast-related transcriptional changes indicated altered osteoclast-associated remodeling, while RANKL–RANK–OPG-related transcripts showed non-coordinated regulation. BAE20 produced the largest 5 dpf transcriptomic response, with changes involving redox response, extracellular matrix regulation, and osteoclast-related processes. Overall, TBBPA-BAE induced stage-dependent, non-monotonic developmental responses characterized by early redox disturbance and later osteoclast-associated skeletal alterations.