Säkkinen Kirsi, Tornaeus Jarkko, Hesso Antti, Hirvonen Ari, Vainio Harri, Norppa Hannu, Rosenberg Christina
Work Environment Development, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FI-00250 Helsinki, Finland.
J Environ Monit. 2011 Apr;13(4):957-65. doi: 10.1039/c0em00595a. Epub 2011 Feb 23.
This work was undertaken to investigate the usefulness of diisocyanate-related protein adducts in blood samples as biomarkers of occupational exposure to toluene diisocyanate (TDI; 2,4- and 2,6-isomers) and 4,4'-methylenediphenyl diisocyanate (MDI). Quantification of adducts as toluene diamines (TDAs) and methylenedianiline (MDA) was performed on perfluoroacylated derivatives by gas chromatography-mass spectrometry (GC-MS/MS) in negative chemical ionisation mode. TDI-derived adducts were found in 77% of plasma and in 59% of globin samples from exposed workers manufacturing flexible polyurethane foam. The plasma levels ranged from 0.003 to 0.58 nmol mL(-1) and those in globin from 0.012 to 0.33 nmol g(-1). The 2,6-isomer amounted to about two-thirds of the sum concentration of TDA isomers. MDI-derived adducts were detected in 3.5% of plasma and in 7% of globin samples from exposed workers manufacturing rigid polyurethane foam. A good correlation was found between the sum of TDA isomers in urine and that in plasma. The relationship between globin adducts and urinary metabolites was ambiguous. Monitoring TDI-derived TDA in plasma thus appears to be an appropriate method for assessing occupational exposure. Contrary to TDI exposure, adducts in plasma or globin were not useful in assessing workers' exposure to MDI. An important outcome of the study was that no amine-related adducts were detected in globin samples from TDI- or MDI-exposed workers, alleviating concerns that TDI or MDI might pose a carcinogenic hazard. Further studies are nevertheless required to judge whether diisocyanates per se could be such a hazard.
开展本研究是为了调查血样中与二异氰酸酯相关的蛋白质加合物作为职业接触甲苯二异氰酸酯（TDI；2,4 - 异构体和2,6 - 异构体）及4,4'-亚甲基二苯基二异氰酸酯（MDI）生物标志物的效用。通过气相色谱 - 质谱联用仪（GC - MS/MS）在负化学电离模式下对全氟酰化衍生物中的加合物进行定量分析，以甲苯二胺（TDAs）和亚甲基二苯胺（MDA）的形式进行测定。在生产软质聚氨酯泡沫的暴露工人的血浆样本中，77%检测到了TDI衍生的加合物，在球蛋白样本中这一比例为59%。血浆中加合物水平范围为0.003至0.58 nmol mL⁻¹，球蛋白中为0.012至0.33 nmol g⁻¹。2,6 - 异构体约占TDA异构体总浓度的三分之二。在生产硬质聚氨酯泡沫的暴露工人的血浆样本中，3.5%检测到了MDI衍生的加合物，在球蛋白样本中这一比例为7%。尿液中TDA异构体总和与血浆中TDA异构体总和之间存在良好的相关性。球蛋白加合物与尿代谢物之间的关系不明确。因此，监测血浆中TDI衍生的TDA似乎是评估职业接触的一种合适方法。与TDI暴露情况相反，血浆或球蛋白中的加合物对于评估工人接触MDI并无用处。该研究的一个重要结果是，在TDI或MDI暴露工人的球蛋白样本中未检测到与胺相关的加合物，这减轻了人们对于TDI或MDI可能构成致癌风险的担忧。然而，仍需要进一步研究来判断二异氰酸酯本身是否可能构成此类风险。
