Toxic Effects of Tetramethyl Bisphenol A on Embryonic–Larval Development of Zebrafish (Danio rerio)

Tetramethyl bisphenol A (TMBPA), a novel alternative to Bisphenol A, is widely used as an industrial flame retardant and a raw material for tetramethyl polycarbonate plastics. With the increasing use of TMBPA, its aquatic ecological risks remain unclear. Therefore, this study investigated the developmental toxicity of TMBPA using zebrafish (Danio rerio) as a model, exposing embryos to 0.5, 5, 50, and 200 μg/L TMBPA for 120 h. The results showed that treatment with 5, 50, and 200 μg/L TMBPA decreased the hatching rate of zebrafish embryos at 48 h post-fertilization (hpf), while no significant difference was observed at 72 hpf. Meanwhile, TMBPA exposure at all concentrations showed no significant effect on the survival rate. Furthermore, a high concentration of TMBPA (200 μg/L) significantly reduced the total length and suppressed swimming ability in zebrafish larvae. In addition, gene expression analysis revealed impacts on antioxidant system (cat, gpx, mn-sod, keap1, ucp2, nrf2), hypothalamic–pituitary–thyroid (HPT) axis (ttr, ugt1ab, trβ), cardiac developmental (tbx2b, myl7, bmp4, notch1b, amhc), and the hypothalamic–pituitary–adrenal (HPA) axis (pomca and nr3c1). The results indicated that TMBPA exposure adversely disrupted embryo hatching and larval development of zebrafish, accompanied by altering the expression of functional genes in larvae. These results provide further evidence for the potential environmental hazard posed by TMBPA.