Synthetic musks (SMs) are odor additives commonly used in the personal care products. Their wide existence in the environment and the recently reported adverse impact on the production and activity of progesterone and estrogen have raised pregnancy red flags and even lead to a pregnancy loss. Apart from the suggestion of limiting SM contact and exposure, effective abortion risk control measures for SMs remain to be blank. Facing the above challenges, this study tried to establish a new theoretical circumvention strategy to reduce the abortion risk of SMs to pregnant women by designing the supplementary diet plan and environmentally friendly SMs derivatives using molecular docking and three-dimensional quantitative structure–activity relationship (3D-QSAR) models. According to the supplementary diet plan, the diet combination of vitamin E, vitamin B₂, niacin, vitamin A, and vitamin B₆ were confirmed to not only provide essential nutrients for human health, but also reduce the abortion risk in pregnant women in daily life. The multi-activity (binding ability of SMs with progesterone-estrogen) 3D-QSAR model was constructed to screen SMs derivatives. The LibDock score, a parameter reflecting the binding ability between SMs’ Derivative-24 with progesterone-estrogen, decreased as much as 137.67% compared with its precursor galaxolide (HHCB). The 3D-QSAR models assisted screening indicated that Derivative-24 had lower environmental impacts (i.e., bioconcentration and mobility) and improved functional properties (odor stability, musky scent, and odor intensity). The integration of the optimum candidate, Derivative-24, with optimum three supplementary diet plans exhibited a much lower abortion risk than HHCB, demonstrating the effectiveness of the proposed theoretical circumvention strategy as a comprehensive abortion risk control measure. It also shed light on the design of new pharmaceutical and personal care products using advanced computing tools.

合成麝香 (SM) 是个人护理产品中常用的气味添加剂。它们在环境中的广泛存在以及最近报道的对黄体酮和雌激素的产生和活性的不利影响已经引发了怀孕危险信号，甚至导致流产。除了限制SM接触和暴露的建议外，针对SM的有效流产风险控制措施仍是空白。面对上述挑战，本研究试图通过分子对接和三维定量构效关系（3D -QSAR) 模型。根据补充饮食计划，维生素E、维生素B的饮食组合₂、烟酸、维生素A、维生素B ₆经证实，不仅可以为人体健康提供必需的营养素，还可以降低孕妇在日常生活中的流产风险。构建了多活性（SMs与孕激素-雌激素的结合能力）3D-QSAR模型来筛选SMs衍生物。LibDock 评分是反映 SM 的 Derivative-24 与孕激素 - 雌激素之间结合能力的参数，与其前体佳乐内酯 (HHCB) 相比下降了 137.67%。3D-QSAR 模型辅助筛选表明，Derivative-24 具有较低的环境影响（即生物浓度和流动性）和改进的功能特性（气味稳定性、麝香气味和气味强度）。最佳候选者 Derivative-24 与最佳三种补充饮食计划的整合显示出比 HHCB 低得多的流产风险，证明所提出的理论规避策略作为综合堕胎风险控制措施的有效性。它还阐明了使用先进计算工具设计新的药品和个人护理产品。