【摘要】 目的 分析六价铬化合物职业接触人群周围全血铬水平与肺功能、遗传损伤指标间的接触-反应关系，提出可溶性六价铬化合物职业接触人群的全血铬生物接触限值。方法 采用回顾性队列研究方法，以六价铬化合物职业接触人群动态队列中某企业2010—2017年515名铬作业工人为研究对象。在文献计量学分析的基础上，对研究对象918次观察结果和队列中的基线数据进行分析，包括肺功能检查、电感耦合等离子体-质谱法测定的全血铬水平、高效液相色谱-质谱联用法测定的尿8-羟基-脱氧鸟苷（8-OHdG）、胞质分裂阻滞微核试验测定的周围血双核淋巴细胞微核率（MNF）和实时荧光定量聚合酶链式反应法测定的线粒体DNA拷贝数（mtCN）。结果 文献计量分析结果显示，近30年国内外六价铬化合物生物监测相关研究逐年增加；其中，全血铬水平可较好地反映六价铬化合物的职业接触情况。六价铬化合物接触人群动态队列中，男性、女性人群总体全血铬水平几何均数分别为2.77和1.79μg/L。当全血铬水平为6.00μg/L时，全血铬水平与肺功能指标、遗传损伤指标的接触-反应曲线均出现转折节点；其中，自然对数转换的全血铬水平每升高1个单位，第1秒用力呼气容积降低0.05 L、1秒率降低0.67%，呼气峰值流量降低0.15 L/s，最大呼气中期流量降低0.09 L/s,MNF增加0.149‰，尿8-OHdG增加0.090μg/g,mtCN增加0.013。当全血铬水平>6.00μg/L时，尿8-OHdG、MNF和mtCN均出现了较大幅度的升高（P值均<0.01）。结论 全血铬水平可作为可溶性六价铬化合物职业接触的生物标志物；初步提出可溶性六价铬化合物职业接触人群全血铬的生物接触限值为6.00μg/L。更多还原

【Abstract】 Objective To analyze the exposure-response relationship of peripheral whole blood chromium level and lung function as well as genetic toxicity indicators in workers exposed to hexavalent chromium [Cr(Ⅵ)] compounds, and to propose a biological exposure limit of whole blood chromium for soluble Cr(Ⅵ) compounds-exposed workers. Methods A total of 515workers from a dynamic occupational Cr(Ⅵ) compounds-exposed cohort in an enterprise from 2010 to 2017 were selected as the research subjects using a retrospective cohort study. A total of 918 followed-up results of research subjects and baseline data of a cohort were analyzed based on bibliometric analysis. The results include lung function tests, whole blood chromium level detected by inductively coupled plasma-mass spectrometry, urinary 8-hydroxy-2′-deoxyguanosine(8-OHdG) detected by high performance liquid chromatography-tandem mass spectrometry, peripheral micronuclei frequency(MNF) detected by cytokinesisblock micronucleus assay, and mitochondrial DNA copy number(mtCN) detected by real-time fluorescence quantitative polymerase chain reaction. Results The results of bibliometric analysis showed that domestic and foreign studies on biological monitoring of Cr( Ⅵ) compounds increased year by year in the past 30 years, and whole blood chromium levels had a good correlation with the occupational Cr(Ⅵ) compounds exposure. The geometric mean of whole blood chromium levels in males and females among the occupational Cr( Ⅵ) compounds exposure cohort was 2.77 and 1.79 μg/L, respectively. A turning point appeared in 6.00 μg/L chromium in whole blood of the exposure-response curve of whole blood chromium levels with lung function indicators and genetic toxicity indicators. For each unit increase in the natural logarithm-transformed whole blood chromium level, the forced expiratory volume in one second(FEV1) decreased by 0.05 L, the FEV1/forced-vital-capacity decreased by 0.67%, the peak expiratory flow decreased by 0.15 L/s, the maximal mid-expiratory flow decreased by 0.09 L/s, the MNF increased by 0.149‰, the urinary 8-OHdG increased by 0.090 μg/g, and the mtCN increased by 0.013. When the whole blood chromium level was >6.00 μg/L, there was a significant increase in urinary 8-OHdG, MNF, and mtCN(all P<0.01).Conclusion The level of whole blood chromium can be used as a biomarker for occupational exposure to soluble Cr( Ⅵ)compounds. The preliminary biological exposure limit is set at 6.00 μg/L for whole blood chromium in workers exposed to soluble Cr(Ⅵ) compounds.更多还原