This study explored the combined disruption mechanism of polychlorinated naphthalenes (PCNs) on the three key receptors (estrogen receptor, thyroid receptor, and adrenoceptor) of the human endocrine system. The intensity of PCN endocrine disruption on these receptors was first determined using a molecular docking method. A comprehensive index of PCN endocrine disruption to human was quantified by analytic hierarchy process and fuzzy analysis. The mode of action between PCNs and the receptors was further identified to screen the molecular characteristics influencing PCN endocrine disruption through molecular docking and fractional factorial design. Quantitative structure–activity relationship (QSAR) models were established to investigate the toxic mechanism due to PCN endocrine disruption. The results showed that the lowest occupied orbital energy (E_LUMO) was the most important factor contributing to the toxicity of PCNs on the endocrine receptors, followed by the orbital energy difference (ΔE) and positive Millikan charge (q⁺). Furthermore, the strategies were formulated through adjusting the nutritious diet to reduce health risk for the workers in PCN contaminated sites and the effectiveness and feasibility were assessed by molecular dynamic simulation. The simulation results indicated that the human health risk caused by PCN endocrine disruption could be effectively decreased by nutritional supplementation. The binding ability between PCNs and endocrine receptors significantly declined (up to −16.45%) with the supplementation of vitamins (A, B₂, B₁₂, C, and E) and carotene. This study provided the new insights to reveal the toxic mechanism of PCNs on human endocrine systems and the recommendations on nutritional supplements for health risk reduction. The methodology and findings could serve as valuable references for screening of potential endocrine disruptors and developing appropriate strategies for PCN or other persistent organic pollution control and health risk management.

本研究探讨了多氯萘 (PCNs) 对人内分泌系统的三个关键受体（雌激素受体、甲状腺受体和肾上腺素受体）的联合破坏机制。PCN 对这些受体的内分泌干扰强度首先使用分子对接方法确定。采用层次分析法和模糊分析法量化PCN对人体内分泌干扰的综合指标。通过分子对接和部分析因设计，进一步确定 PCN 与受体之间的作用模式，以筛选影响 PCN 内分泌干扰的分子特征。建立了定量构效关系 (QSAR) 模型来研究 PCN 内分泌干扰引起的毒性机制。_LUMO ) 是导致 PCNs 对内分泌受体产生毒性的最重要因素，其次是轨道能量差 (ΔE) 和密立根正电荷 (q ⁺ )。此外，通过调整营养膳食来降低PCN污染场地工人的健康风险，并通过分子动力学模拟评估了有效性和可行性。模拟结果表明，通过营养补充可以有效降低PCN内分泌紊乱引起的人体健康风险。PCNs 与内分泌受体的结合能力在补充维生素 (A, B ₂ , B ₁₂、C 和 E) 和胡萝卜素。本研究为揭示 PCNs 对人体内分泌系统的毒性机制以及降低健康风险的营养补充剂建议提供了新的见解。该方法和研究结果可以作为有价值的参考，用于筛选潜在的内分泌干扰物和制定适当的 PCN 或其他持久性有机污染控制和健康风险管理策略。