Environmental occurrence and human exposure of emerging organophosphate esters (eOPEs) have increased significantly in recent years. Resorcinol bis(diphenyl) phosphate (RDP) is one of the major eOPEs detected in indoor dust, but the knowledge on its toxicities and health risks is rather limited. In this study, we investigated the in vitro estrogenic effects and underlying mechanism of RDP in comparison with a legacy OPE triphenyl phosphate (TPHP). Our results showed that RDP promoted MCF-7 cell proliferation with the lowest effect concentration of 2.5 μM, and the maximum enhancement of 1.6 folds is greater than that of TPHP (1.3 folds). The effect was inhibited completely by an estrogen receptor (ER) antagonist, suggesting that ER activation was responsible for the enhancement. In luciferase reporter gene assays both RDP and TPHP activated ER transcriptional activity at 2.5 μM, but RDP activity was higher than TPHP. Competitive fluorescence binding assays showed that RDP bound to ER with an IC₁₀ of 0.26 μM, which is 20 folds lower than TPHP (5.6 μM). Molecular docking simulation revealed that both RDP and TPHP interacted with ER at the binding pocket of estradiol, although the hydrogen bonds were different. Taken together, RDP exerted stronger estrogenic effects than TPHP through ER-mediated pathways and may pose more health risks.

近年来，新兴有机磷酸酯（eOPE）的环境发生率和人类暴露量显着增加。间苯二酚双（二苯基）磷酸酯（RDP）是室内灰尘中检测到的主要 eOPE 之一，但对其毒性和健康风险的了解相当有限。在这项研究中，我们研究了 RDP 与传统 OPE 磷酸三苯酯 (TPHP) 的体外雌激素作用和潜在机制。结果显示，RDP促进MCF-7细胞增殖的最低作用浓度为2.5 μM，最大增强1.6倍，大于TPHP（1.3倍）。该作用被雌激素受体（ER）拮抗剂完全抑制，表明ER 激活是增强作用的原因。在荧光素酶报告基因检测中，RDP 和 TPHP 在 2.5 μM 时均激活 ER 转录活性，但 RDP 活性高于 TPHP。竞争性荧光结合测定表明，RDP 与 ER 结合的 IC ₁₀为 0.26 μM，比 TPHP (5.6 μM) 低 20 倍。分子对接模拟表明，RDP 和 TPHP 均在雌二醇的结合口袋处与 ER 相互作用，尽管氢键不同。总而言之，RDP 通过 ER 介导的途径发挥比 TPHP 更强的雌激素作用，并可能带来更多的健康风险。