Bisphenol A (BPA) and bisphenol F (BPF) are widely distributed in the environment and daily consumptions, leading to exposure toward human and environmental animals. The potential risk of bisphenol analogs on pigment and skin health is not well documented. In this study, we found that 0.05 mg/L BPF (tolerated daily intake (TDI) value of BPA) affected the particle size and color density of zebrafish melanin. While BPA caused less depigmentation effect toward zebrafish with effective concentration of 5.0 mg/L. The downregulation of melanin synthases induced by BPF is associated with the reduction in melanin. Molecular dynamics indicated that both BPF and BPA could act as ligands of zebrafish and human Tyr family proteins; however, these compounds have completely different energetics and spatial steric effects, potentially explaining their varying depigmentation effects. Additionally, an in vitro assay using A375 melanoma cells demonstrated that the inhibitory effect of BPF on human melanin production was primarily attributed to Tyr inhibition. These findings provide an important basis for understanding the molecular mechanisms of BPF and BPA in melanin inhibition, and the results reflect the skin pigmentation interference risk of these compounds, which are ubiquitous in everyday personal products.

双酚A（BPA）和双酚F（BPF）广泛分布于环境和日常消费中，导致人类和环境动物接触。没有充分记录双酚类似物对色素和皮肤健康的潜在风险。在这项研究中，我们发现0.05 mg / L的BPF（BPA的每日允许摄入量（TDI）值）会影响斑马鱼黑色素的粒径和颜色密度。有效浓度为5.0 mg / L的BPA对斑马鱼的脱色作用较小。BPF诱导的黑色素合酶的下调与黑色素的减少有关。分子动力学表明，BPF和BPA均可作为斑马鱼和人类Tyr家族蛋白的配体。但是，这些化合物具有完全不同的能量和空间位阻效应，可能解释了它们不同的脱色效果。此外，使用A375黑色素瘤细胞进行的体外分析表明，BPF对人黑色素生成的抑制作用主要归因于Tyr抑制。这些发现为理解BPF和BPA抑制黑色素的分子机理提供了重要依据，并且结果反映了这些化合物在日常个人产品中无处不在的皮肤色素沉着干扰风险。