目的:探讨苯、甲苯、二甲苯联合职业接触相关的生物标志物，探索苯、甲苯、二甲苯联合职业接触致机体早期健康效应的机制。方法:于2018年5月，选择某制鞋厂的40名女性职工，其中从事苯、甲苯、二甲苯联合接触岗位职工作为接触组，共20人；该企业后勤行政人员作为对照组，共20人。用自制调查问卷进行基本信息收集，并收集研究对象的尿液。利用液相色谱飞行时间质谱联用仪采集样品的代谢轮廓，采用专业代谢组学和多变量统计分析软件建立无监督主成分分析（PCA）和有监督正交偏最小二乘法-判别分析（OPLS-DA）模型筛选潜在的生物标志物并对潜在生物标志物进行鉴定。结果:与对照组比较，接触组的年龄、BMI、吸烟和饮酒情况的差异无统计学意义（n P>0.05）。尿液代谢组学分析结果显示，对照组和接触组的代谢轮廓存在明显的差异，筛选并鉴定出与苯、甲苯、二甲苯联合接触密切相关的潜在生物标志物27个。这些潜在生物标志物在16条代谢通路中富集，其中3条通路明显富集（n P<0.05），分别为赖氨酸代谢、氨基糖代谢和核苷酸糖代谢。n 结论:代谢组学方法较好的反映职业人群受苯、甲苯、二甲苯联合接触后尿样代谢组改变的状况。“,”Objective:To study the effects of combined occupational exposure of benzene, toluene, and xylene on human metabolism at an overall level, and to screen biomarkers related to the combined occupational exposure of benzene, toluene, and xylene, and to explore the mechanism of early health effects preliminarily caused by combined occupational exposure of benzene, toluene, and xylene by identification of biomarkers and retrieval of metabolic pathways.Methods:A shoe-making company was selected as the research site. Twenty subjects for the exposed group and the control group were selected separately, and urine of the subjects was collected. The metabolic profiles of the samples were collected by liquid chromatography time-of-flight mass spectrometry, and professional metabolomics and multivariate statistical analysis software were used to establish PCA and OPLS-DA analysis models to screen potential biomarkers and identify biomarkers. Finally, based on the dynamic changes and trends of potential biomarkers between groups, the mechanism of body damage caused by benzene, toluene, and xylene was initially explored.Results:Urine metabolomics analysis showed that the metabolic profile of urine samples of the benzene, toluene, and xylene combined exposure group was different from that of the control group. 27 potential biomarkers that were closely related to the combined exposure of benzene, toluene, and xylene were screened and identified. These potential biomarkers were enriched in 16 metabolic pathways, of which 3 pathways were significantly enriched (n P<0.05) , respectively, lysine metabolism, amino sugar metabolism, and nucleotide sugar metabolism.n Conclusion:The metabonomics method can well reflect the changes in the metabolome of urine samples in the occupational population after the combined exposure of benzene, toluene, and xylene, which will help us better evaluate the risk of combined exposure of benzene, toluene, and xylene and prevent and control their health risks.