Resorcinol bis(diphenyl phosphate) (RDP), an emerging organophosphorus flame retardant and alternative to triphenyl phosphate (TPHP), is a widespread environmental pollutant. The neurotoxicity of RDP has attracted much attention, as RDP exhibits a similar structure to TPHP, a neurotoxin. In this study, the neurotoxicity of RDP was investigated by using a zebrafish (Danio rerio) model. Zebrafish embryos were exposed to RDP (0, 0.3, 3, 90, 300 and 900 nM) from 2 to 144 h postfertilization. After this exposure, the decreased heart rates and body lengths and the increased malformation rates were observed. RDP exposure significantly reduced the locomotor behavior under light-dark transition stimulation and the flash stimulus response of larvae. Molecular docking results showed that RDP could bind to the active site of zebrafish AChE and that RDP and AChE exhibit potent binding affinity. RDP exposure also significantly inhibited AChE activity in larvae. The content of neurotransmitters (γ-aminobutyric, glutamate, acetylcholine, choline and epinephrine) was altered after RDP exposure. Key genes (α1-tubulin, mbp, syn2a, gfap, shhα, manf, neurogenin, gap-43 and ache) as well as proteins (α1-tubulin and syn2a) related to the development of the central nervous system (CNS) were downregulated. Taken together, our results showed that RDP can affect different parameters related to CNS development, eventually leading to neurotoxicity. This study indicated that more attention should be paid to the toxicity and environmental risk of emerging organophosphorus flame retardants.

间苯二酚双（磷酸二苯酯）（RDP）是一种新兴的有机磷阻燃剂，是磷酸三苯酯（TPHP）的替代品，是一种广泛存在的环境污染物。RDP的神经毒性引起了广泛关注，因为RDP与神经毒素TPHP具有相似的结构。在本研究中，使用斑马鱼（Danio rerio）研究了 RDP 的神经毒性） 模型。受精后 2 至 144 小时，斑马鱼胚胎暴露于 RDP（0、0.3、3、90、300 和 900 nM）。暴露后，观察到心率和体长下降，畸形率增加。RDP暴露显着降低了幼虫在明暗转换刺激下的运动行为和闪光刺激反应。分子对接结果表明，RDP可以与斑马鱼AChE的活性位点结合，并且RDP和AChE表现出有效的结合亲和力。RDP 暴露还显着抑制幼虫中的 AChE 活性。接触 RDP 后，神经递质（γ-氨基丁酸、谷氨酸、乙酰胆碱、胆碱和肾上腺素）的含量发生变化。关键基因 ( α1-微管蛋白, mbp , syn2a , gfap、shhα、manf、神经生成素、gap - 43和ache）以及与中枢神经系统（CNS）发育相关的蛋白质（α1-微管蛋白和 syn2a）被下调。综上所述，我们的结果表明，RDP 可以影响与中枢神经系统发育相关的不同参数，最终导致神经毒性。这项研究表明，应更加关注新兴有机磷阻燃剂的毒性和环境风险。