Toxic effects of bisphenol M, a bisphenol A substitute, on early developmental stages of marine medaka (Oryzias...

Bisphenols have been detected in various aquatic environments, with total concentrations reaching 262.2 ng/L in European rivers and 62.0 ng/L in the East China Sea, raising concerns about their ecological impacts. Among these compounds, bisphenol M (BPM; 4,4'-(1,3-phenylenediisopropylidene) bisphenol), a substitute for bisphenol A, was predicted in our previous computational toxicology study to pose high acute toxicity to aquatic organisms. To experimentally validate this prediction and address the existing toxicological data gap, the toxicity of BPM was investigated using marine medaka (Oryzias melastigma) embryos. The 96 h median lethal concentration (LC₅₀) of BPM was determined to be 2.7 mg/L. BPM exposure exerted a biphasic effect on hatchability, with an 18.1% increase at 0.5 μg/L but an 11.1% decrease at 500 μg/L. Furthermore, exposure to BPM (0.05-500 μg/L) induced morphological abnormalities, including spinal curvature and yolk-sac edema. Cardiac and neurological functions were also impaired, with heart rate reduced by 33.0% at 0.05 μg/L and swimming speed decreased by 53.5% at 5 μg/L. Transcriptional profiling revealed consistent upregulation of estrogen-responsive genes (esr, vtg, and cyp19) and altered expression of thyroid signaling components (tbg, tr, and tshβ), suggesting multi-level endocrine interference. These findings confirm the earlier computational prediction and establish BPM as a potent developmental toxicant and endocrine disruptor, providing critical evidence for ecological risk assessment of bisphenol alternatives.