Pharmaceuticals and personal care products (PPCPs) as emerging contaminants are ubiquitously present in the aquatic environment. Using in vivo and in silico techniques, this study aims to elucidate tissue distribution and endocrine disruption effects of chronic exposure (120 days) to PPCP mixture at environmentally relevant concentrations (ERCs) in adult zebrafish. Results from UHPLC-MS/MS analyses showed elevated distribution of PPCPs in zebrafish tissues in the order of liver > gonad > brain. Upregulation of steroid hormone receptors, both gonadotropin, and steroidogenic genes perturb the HPG axis pathway in females, while male fish exhibited significantly downregulated expressions of vtg, cyp17, and 17βhsd genes with inhibited fecundity. The Spearman correlation indicated a significant positive relationship between PPCPs bioaccumulation and mRNA levels of HPG axis genes. In silico molecular docking (MD) revealed specific amino acid residues of PPCPs binding with zebrafish estrogen receptors. Furthermore, the strongest binding energies of sulfamethoxazole, carbamazepine, and triclosan were discovered in erα and erβ estrogen receptors, confirming PPCPs' xenoestrogenic behavior. To summarize, chronic exposure to ERCs resulted in a high accumulation of PPCPs in the liver and gonad tissues of adult zebrafish, as well as associated perturbed genetic responses. As a result, strict environmental regulations for the disposal of PPCPs should be ensured to protect ecological and public health.

药物和个人护理产品 (PPCP) 作为新兴污染物普遍存在于水生环境中。本研究使用体内和计算机技术，旨在阐明成年斑马鱼长期接触环境相关浓度 (ERC) PPCP 混合物（120 天）对组织分布和内分泌干扰的影响。UHPLC-MS/MS 分析结果显示斑马鱼组织中 PPCP 的分布升高，顺序为肝脏 > 性腺 > 脑。类固醇激素受体（促性腺激素和类固醇生成基因）的上调扰乱了雌性的 HPG 轴通路，而雄性鱼的vtg、cyp17和17βhsd 的表达显着下调生育力受抑制的基因。Spearman 相关性表明 PPCPs 生物积累与 HPG 轴基因的 mRNA 水平之间存在显着的正相关。计算机分子对接 (MD) 揭示了与斑马鱼雌激素受体结合的 PPCP 的特定氨基酸残基。此外，在erα和erβ中发现磺胺甲恶唑、卡马西平和三氯生的最强结合能雌激素受体，证实了 PPCPs 的异种雌激素行为。总而言之，长期暴露于 ERC 导致成年斑马鱼肝脏和性腺组织中 PPCP 的大量积累，以及相关的扰乱遗传反应。因此，应确保对 PPCP 的处置制定严格的环境法规，以保护生态和公众健康。