Sennbro Carl Johan, Littorin Margareta, Tinnerberg Håkan, Jönsson Bo A G
Department of Occupational and Environmental Medicine, University Hospital, 221 85 Lund, Sweden.
Int Arch Occup Environ Health. 2005 Aug;78(7):541-6. doi: 10.1007/s00420-005-0619-5. Epub 2005 Jul 2.
The objectives of this study were to determine the levels of 2,4-toluenediamine, 2,6-toluenediamine, 1,5-naphthtalenediamine and 4,4'-methylenediphenyldianiline in hydrolyzed urine and plasma for occupationally unexposed workers and to calculate upper reference limits (URLs). These analytes are biomarkers of exposure to 2,4-toluene diisocyanate and 2,6-toluene diisocyanate (2,4-TDI and 2,6-TDI), 1,5-naphtalene diisocyanate (NDI) and 4,4'-methylenediphenyl diisocyanate (MDI), respectively.
The biomarker levels were determined in urinary and plasma samples obtained from 121 occupationally unexposed workers. Based on these biomarkers levels and the biomarker levels in an occupationally exposed group of workers, URLs were calculated. The method used for these calculations was based on the receiver operator characteristic (ROC) curve method technique, and the URLs were set at the optimum of sum of sensitivity and specificity.
The URLs for the different diisocyanates were calculated to be in the range of 0.1-0.5 microg/L. Occupationally unexposed workers had detectable biomarker levels of the diisocyanates investigated. Especially abundant was the biomarkers of MDI which were found in 97% of both urinary and plasma samples. For the other biomarkers, 0-15% of the unexposed workers had detectable levels. The detected levels were mostly close to the limit of detection (LOD), but urinary levels of biomarkers of MDI up to 60 times the LOD were found. The sensitivities and specificities for classification of the workers as occupationally exposed or not, were in the range of 88-100% and 97-100%, respectively.
The URLs were calculated that may be applicable when screening for occupational exposure. A worker with a biomarker level above the URL will be classified as occupationally exposed. Biomarkers of aromatic diisocyanates, especially biomarkers of MDI, were present among occupationally unexposed workers, but the source and nature of the exposure is unknown.
本研究的目的是测定职业未暴露工人水解尿液和血浆中2,4 - 甲苯二胺、2,6 - 甲苯二胺、1,5 - 萘二胺和4,4'- 亚甲基二苯基二胺的水平，并计算参考上限（URLs）。这些分析物分别是接触2,4 - 甲苯二异氰酸酯和2,6 - 甲苯二异氰酸酯（2,4 - TDI和2,6 - TDI）、1,5 - 萘二异氰酸酯（NDI）和4,4'- 亚甲基二苯基二异氰酸酯（MDI）的生物标志物。
测定了从121名职业未暴露工人采集的尿液和血浆样本中的生物标志物水平。基于这些生物标志物水平以及一组职业暴露工人的生物标志物水平，计算了URLs。用于这些计算的方法基于受试者工作特征（ROC）曲线法技术，URLs设定在敏感性和特异性之和的最佳值处。
不同二异氰酸酯的URLs计算值在0.1 - 0.5微克/升范围内。职业未暴露工人中可检测到所研究二异氰酸酯的生物标志物水平。MDI的生物标志物尤其丰富，在尿液和血浆样本中均有97%的样本检测到。对于其他生物标志物，0 - 15%的未暴露工人有可检测水平。检测到的水平大多接近检测限（LOD），但发现尿液中MDI生物标志物水平高达LOD的60倍。将工人分类为职业暴露或未暴露的敏感性和特异性分别在88 - 100%和97 - 100%范围内。
计算出的URLs可能适用于职业暴露筛查。生物标志物水平高于URL的工人将被分类为职业暴露。职业未暴露工人中存在芳香族二异氰酸酯的生物标志物，尤其是MDI的生物标志物，但暴露的来源和性质尚不清楚。
