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Trisaminohexyl Isocyanurate, a Biomarker for HDI Isocyanurate Exposure

机译:三氨基己基异氰脲酸盐,一种用于HDI异氰脲酸酯暴露的生物标志物

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Exposures to monomeric and polymeric 1,6-hexamethylene diisocyanate (HDI) in the automotive refinishing industry have been well characterized. However, biological monitoring is limited to a hydrolysis product of HDI monomer, 1,6-hexamethylene diamine (HDA). Further, inhalation and skin exposures to HDI monomer during painting operations are low compared to its oligomers. HDI isocyanurate constitutes the largest fraction of inhalation and skin exposures in automotive spray paints and has been shown to possess a greater sensitizing capacity than HDI monomer. Additionally, HDI isocyanurate penetrates the skin at a faster rate than HDI monomer, emphasizing the need to shift research focus towards the fate of HDI isocyanurate after exposure. We have developed a sensitive and specific method to quantify trisaminohexyl isocyanurate (TAHI), a hydrolysis product of HDI isocyanurate, in urine. Two end of day urine samples were collected from two spray painters exposed to HDI isocyanurate during automotive spray-painting operations. Urine samples were hydrolyzed with sulfuric acid, made basic with sodium hydroxide, and extracted with dichloromethane. The extracts were derivatized with acetic anhydride and excess reagent was removed with phosphate buffer and sodium sulfate before sample was dried and reconstituted with water for analysis. A calibration curve was created by spiking urine from non-exposed persons with the synthesized standard TAHI with a concentration range of 0.04-5.00 μg/L and a synthesized internal standard trisaminoheptyl isocyanurate (TAHpl; 2.5 μg/L). Samples were analyzed with nanoUPLC-ESI-MS/MS for the precursor ions m/z 553.3 (trisacetamidohexyl isocyanurate, TAAHI) and m/z 595.3 (trisacetamidoheptyl isocyanurate, TAAHpl) using selected reaction monitoring. Urine samples collected from two workers with significant breathing-zone and skin exposure to HDI monomer (breathing zone: 216 and 79.5 ug/m3; skin: 8.3 and 1.3 ug/mm3) and HDI isocyanurate (breathing zone: 65432.3 and 20926.6 μg/m3; skin: 3949.1 and 366.0 ug/mm3) had TAHI levels of 0.43 and 2.29 μg/L, respectively, while HDA concentrations in the same samples were 0.21 and 0.37 μg/L, respectively. The results indicate that this method can be used to quantitate HDI isocyanurate biomarker TAHI in urine of exposed workers. Quantitation of HDI isocyanurate biomarker in urine in conjunction with HDI monomer biomarker from workers exposed to HDI-containing spray paints will aid in the investigation of the adverse effects of inhalation and skin exposure and individual susceptibility in exposed workers.
机译:暴露在汽车修补行业单体和聚合的1,6-己二异氰酸酯(HDI)已经被很好地表征。然而,生物监测被限制为HDI单体,1,6-六亚甲基二胺(HDA)的水解产物。此外,涂装操作期间吸入和皮肤暴露于HDI单体低相比,它的低聚物。 HDI异氰脲酸酯构成在汽车喷漆吸入和皮肤接触的最大部分,并已被证明具有比HDI单体更大的敏化能力。此外,HDI异氰脲酸酯穿透皮肤以更快的速度比HDI单体,强调对HDI异氰脲酸酯曝光以后的命运需要转移的研究重点。我们已经发展到Quantify的trisaminohexyl异氰脲敏感和特异的方法(TAHI),HDI异氰脲酸酯的水解产物,尿液中。当天尿样的两端从在汽车喷漆操作暴露于HDI异氰脲酸酯两名画家收集。尿液样品用硫酸进行水解,用氢氧化钠,并用二氯甲烷萃取。的萃取液用乙酸酐衍生,并用磷酸盐缓冲液和硫酸钠除去过量的试剂样品干燥后,用水重构分析前。 (2.5微克/升TAHpl)的校准曲线是由尖峰的尿从非曝光者与合成标准TAHI具有0.04-5.00微克/升的浓度范围和合成内标trisaminoheptyl异氰脲酸酯创建。样品使用选择反应监测与nanoUPLC-ESI-MS /对前体离子的MS M / Z 553.3(trisacetamidohexyl异氰脲酸酯,TAAHI)和m / z 595.3(trisacetamidoheptyl异氰脲酸酯,TAAHpl)进行分析。从两个工人显著呼吸区和皮肤暴露于HDI单体收集尿液样品(呼吸区:216和79.5微克/立方米;皮肤:8.3和1.3微克/立方毫米)和HDI异氰脲酸酯(呼吸区:65432.3和20926.6微克/立方米;皮肤:3949.1和366.0微克/立方毫米)具有分别为0.43 TAHI水平和2.29微克/升,而同一样品在HDA浓度分别为0.21和0.37微克/升,分别。实验结果表明,该方法可在尿液中暴露的工人被用于定量HDI异氰脲酸酯生物标志物TAHI。从暴露于含HDI-喷漆工人尿中与HDI单体的生物标记结合HDI异氰脲酸酯生物标志物的定量将在吸入和皮肤接触和暴露的工人个体易感性的不利影响调查协助。

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