Dermal Exposure to 1,6-Hexamethylene Diisocyanate

描述（由申请人提供）：我们建议开发和应用1,6-六亚甲基二异氰酸酯（HDI）暴露的测量方法，这些方法适用于具有致敏性和职业性哮喘发展风险的喷漆工。该问题的重要性和明确定义的“高危”研究人群的可用性保证了这项拟议研究的全面性。为了实现这一目标，我们将从一个美国海军基地招募50名喷漆工。使用Iso-Check TM采样器测量个人呼吸区暴露。将分析血液和尿液样本的代谢物1,6-六亚乙二胺（HDA）作为全身暴露和全身吸收的标志。皮肤沉积和进入角质层的渗透将使用非侵入性胶带剥离方法进行测量。将开发一种用于检测HDI内合角蛋白的酶联免疫吸附试验（ELISA）方法，以测量HDI通过皮肤的吸收和潜在的全身生物利用度。发展测量皮肤中HDI加合物的能力将使我们能够确定暴露的动力学和剂量学。我们将通过开发的方法（ELISA和/或从角质化皮肤中提取HDI）将测量的真皮浓度与其他前哨介质（尿液或血浆中的HDA）的浓度联系起来。总之，这些数据将使我们能够将皮肤暴露与全身暴露联系起来，并确定通过皮肤暴露的重要性。生物有效剂量与生物标本中测量到的剂量之间的相关性对于了解通过皮肤暴露的HDI的作用至关重要。最后，我们将能够使用混合效应线性回归模型确定与工作分类和工作任务相关的因素如何影响职业暴露工人近期皮肤暴露于HDI，并开发喷涂暴露模型来预测皮肤沉积率，并在实验室和现场环境中评估这些预测。通过将工业卫生调查与所有潜在途径的暴露测量、生物有效剂量测量和复杂的暴露建模相结合，本研究开发的方法和获得的结果将有助于理解皮肤暴露作为全身暴露载体的作用，以及制定测量和减少皮肤暴露的策略。

DESCRIPTION (provided by applicant): We propose to develop and apply methods for measurement of 1,6-hexamethylene diisocyanate (HDI) exposure of spray painters who are at risk for sensitization and development of occupational asthma. The importance of the problem and the availability of a well-defined "at-risk" study population warrant the comprehensive nature of this proposed research. To achieve this goal, we will recruit 50 spray painters from one U.S. Marine/Navy base. Personal breathing-zone exposure will be measured with the Iso-Check TM sampler. Blood and urine samples will be analyzed for the metabolite 1,6-hexamethylene diamine (HDA) as a marker for whole body exposure and systemic absorption. Dermal deposition and penetration into the stratum corneum will be measured using a non-invasive tape-stripping method. An enzyme-linked immunosorbent assay (ELISA) method for detection of HDI-adducted keratin will be developed in order to measure HDI absorption and the potential systemic bioavailability via the skin. Development of the capacity to measure adducts of HDI in the skin will allow us to define the kinetics and dosimetry of exposure(s). We will correlate the measured dermal concentration by the developed methods (ELISA and/or HDI extracted from the keratinized skin) with concentrations in other sentinel media (HDA in urine or plasma). Together, these data will allow us to correlate dermal exposure to systemic exposure and to determine the significance of exposure through the skin. Correlation between the biologically available dose and the dose measured in the biological specimens is critical to developing an understanding of the role of HDI exposure through the skin. Finally, we will be able to determine how factors related to job classification and work tasks affect recent dermal exposure to HDI in occupationally exposed workers using mixed-effects linear-regression models and to develop a model for spray painting exposure to predict dermal deposition rates and to evaluate these predictions in laboratory and field settings. By combining a industrial hygiene survey with measurements of exposure through all potential routes, with measurements of biologically available dose and sophisticated exposure modeling, the methods developed and results obtained by this study will be valuable for understanding of the role of dermal exposure as a vehicle for systemic exposure and for developing strategies to measure and minimize dermal exposure.