Fluorene-9-bisphenol (BHPF) is a bisphenol A substitute, which has been introduced for the production of so-called ‘bisphenol A (BPA)-free’ plastics. However, it has been reported that BHPF can enter living organisms through using commercial plastic bottles and cause adverse effects. To date, the majority of the toxicologic study of BHPF focused on investigating its doses above the toxicological threshold. Here, we studied the effects of BHPF on development, locomotion, neuron differentiation of the central nervous system (CNS), and the expression of genes in the hypothalamic-pituitary-thyroid (HPT) axis in zebrafish exposed to different doses of BHPF ranging from 1/5 of LD1 to LD50 (300, 500, 750, 1500, 3000, and 4500 nM). As a result, the possible hormetic effects of BHPF on regulating the HPT axis were revealed, in which low-dose BHPF positively affected the HPT axis while this regulation was inhibited as the dose increased. Underlying mechanism investigation suggested that BHPF disrupted myelination through affecting HPT axis including related genes expression and TH levels, thus causing neurotoxic characteristics. Collectively, this study provides the full understanding of the environmental impact of BHPF and its toxicity on living organisms, highlighting a substantial and generalized ongoing dose-response relationship with great implications for the usage and risk assessment of BHPF.

芴9-双酚（BHPF）是双酚A的替代品，已被引入生产所谓的“不含双酚A（BPA）”的塑料。然而，据报道，必和必拓可通过使用商业塑料瓶进入生物体内并产生不利影响。迄今为止，BHPF的大部分毒理学研究都集中在调查其高于毒理学阈值的剂量。在这里，我们研究了BHPF对斑马鱼暴露于不同剂量的BHPF的发育，运动，中枢神经系统（CNS）神经元分化以及下丘脑-垂体-甲状腺（HPT）轴中基因表达的影响。 LD1至LD50的1/5（300、500、750、1500、3000和4500 nM）。结果揭示了BHPF对调节HPT轴可能产生的抑制作用，其中低剂量的BHPF对HPT轴有积极影响，而随着剂量的增加，这种调节受到抑制。潜在的机制研究表明，BHPF通过影响HPT轴（包括相关基因表达和TH水平）破坏了髓鞘形成，从而引起了神经毒性。总的来说，这项研究提供了对BHPF的环境影响及其对活生物体的毒性的全面理解，强调了一个广泛的，持续的剂量反应关系，对BHPF的使用和风险评估具有重要意义。从而引起神经毒性。总的来说，这项研究提供了对BHPF的环境影响及其对活生物体的毒性的全面理解，强调了一个广泛的，持续的剂量反应关系，对BHPF的使用和风险评估具有重要意义。从而引起神经毒性。总的来说，这项研究提供了对BHPF的环境影响及其对活生物体的毒性的全面理解，强调了一个广泛的，持续的剂量反应关系，对BHPF的使用和风险评估具有重要意义。