Bio-monitoring Methylene Diphenyl Diisocyanate (MDI) exposure and body burden

生物监测亚甲基二苯基二异氰酸酯 (MDI) 暴露和身体负担

• 批准号: 7804011
• 负责人: ADAM WISNEWSKI
• 金额: $ 21.15万
• 依托单位: L2 DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7804011
• 关键词: Affinity; Albumins; Amino Acids; Antibodies; Antigens; Asthma; Binding; Biological Assay; Biological Markers; Body Burden; Cell Line; Characteristics; Chemicals; Consumption; Data; Development; Elastomers; Ensure; Enzymes; Epitopes; Exposure to; Health; Heating; Human; Hybridomas; Immunoassay; Immunoglobulin G; Isocyanates; Laboratories; Link; Liquid substance; Marketing; Measures; Methods; Monitor; Monoclonal Antibodies; Mus; Occupational Asthma; Oryctolagus cuniculus; Phase; Plasma; Polyurethanes; Production; Property; Proteins; Reagent; Relative (related person); Research Personnel; Respiratory System; Respiratory tract structure; Risk Factors; Safety; Serum; Site; Solid; Specificity; Surveillance Program; Temperature; Time; Toluene Diisocyanate; Vision; Work; Workplace; aerosolized; base; carbene; cross reactivity; diphenyl; disorder prevention; experience; flexibility; improved; novel strategies; peripheral blood; pressure; programs; public health relevance; vapor

DESCRIPTION (provided by applicant): Exposure to isocyanate, the essential cross-linker for making polyurethane, is a leading cause of occupational asthma world-wide. Three major types of isocyanate are used commercially, methylene-diphenyl diisocyanate (MDI) and toluene diisocyanate (TDI), or aliphatic, hexamethylene diisocyanate (HDI). Despite being the newest of the three, MDI has overtaken the isocyanate market in production and consumption, for many reasons, including its unique applications and properties. Importantly, at room temperature, MDI has a much lower vapor pressure than HDI or TDI, and exists as a solid, rather than a (volatile) liquid. Thus, MDI is presumed to be "safer", because the potential for respiratory tract exposure is thought to be restricted to times when the chemical is heated or aerosolized (sprayed), i.e. during application. MDI is widely used in making flexible and rigid foams, coatings, elastomers and numerous other polyurethane-based products. Exposure to MDI is the best-recognized risk factor for the development of MDI asthma and exposure reduction is the primary strategy of disease prevention. Contemporary methods of monitoring MDI exposure are severely limited, and new approaches are needed to help protect millions of people exposed at work. Our laboratory is currently investigating new approaches to MDI exposure surveillance based upon serum biomarkers, which offer distinct advantages over (workplace) environmental surveillance. Our new approach uses immunoassays to quantitate two biomarkers we hypothesize provide important MDI exposure information and, which can greatly improve current surveillance programs. One biomarker is MDI-specific IgG, which should serve as an effective exposure surrogate, according to principles we outline in the Background (Section B), and can be measured through an indirect enzyme-linked immunosorbant assays (ELISA). A second biomarker is MDI itself, circulating in the peripheral blood attached to self proteins, which we propose to "capture" in a "sandwich"-type ELISA. Our vision is for these serum biomarkers, and immunoassays for their quantitation, to become part of integrated multi-disciplinary MDI exposure monitoring programs, which help protect the health of millions of workers throughout the world. Development of the proposed immunoassays will be facilitated by previous experience of the research personnel, and preliminary data acquired to date. The Specific Aims of the project are the following: Aim 1) Generate and characterize candidate MDI (conjugated albumin) antigens. Aim 2) Develop methods to measure MDI-specific antibodies (biomarker 1). Aim 3) Generate and characterize (rabbit) polyclonal and (mouse) monoclonal MDI-specific antibodies. Aim 4) Develop immunoassays that detect and quantitate MDI in human serum (biomarker 2). PUBLIC HEALTH RELEVANCE: This application will develop two new immunoassays to bio-monitor MDI exposure in the workplace, thus, ensuring adequate safety in polyurethane manufacture, and protecting the health of the US workforce.

描述（由申请人提供）：暴露于异氰酸酯（制造聚氨酯的基本交联剂）是全球职业性哮喘的主要原因。三种主要类型的异氰酸酯在商业上使用，亚甲基二苯基二异氰酸酯（MDI）和甲苯二异氰酸酯（TDI），或脂肪族二异氰酸酯（HDI）。尽管MDI是三种产品中最新的一种，但由于其独特的应用和性能等原因，MDI在生产和消费方面已经超过了异氰酸酯市场。重要的是，在室温下，MDI的蒸气压比HDI或TDI低得多，并且以固体而不是（挥发性）液体存在。因此，计量吸入器被认为是“更安全的”，因为呼吸道接触的可能性被认为仅限于化学品加热或雾化（喷雾）的时间，即在使用过程中。MDI广泛用于制造软质和硬质泡沫、涂料、弹性体和许多其他基于聚氨酯的产品。暴露于MDI是MDI哮喘发展的最佳公认风险因素，减少暴露是疾病预防的主要策略。监测计量吸入器接触的现代方法受到严重限制，需要新的方法来帮助保护数百万在工作中接触的人。 我们的实验室目前正在研究基于血清生物标志物的MDI暴露监测的新方法，该方法比（工作场所）环境监测具有明显的优势。我们的新方法使用免疫测定来定量两种生物标志物，我们假设这两种生物标志物提供了重要的MDI暴露信息，这可以大大改善目前的监测计划。一种生物标志物是MDI特异性IgG，根据我们在背景（第B节）中概述的原则，它应该作为有效的暴露替代品，并且可以通过间接酶联免疫吸附试验（ELISA）进行测量。第二种生物标志物是MDI本身，在外周血中循环，附着在自身蛋白上，我们建议在“三明治”型ELISA中“捕获”。我们的愿景是让这些血清生物标志物及其定量免疫测定成为综合多学科MDI暴露监测计划的一部分，帮助保护全球数百万工人的健康。研究人员先前的经验和迄今为止获得的初步数据将促进拟定免疫测定的开发。该项目的具体目的如下：目的1）生成和表征候选MDI（结合白蛋白）抗原。目的2）开发测量MDI特异性抗体（生物标志物1）的方法。目的3）制备和表征（兔）多克隆和（小鼠）单克隆MDI特异性抗体。目的4）开发检测和定量人血清中MDI（生物标志物2）的免疫测定法。 公共卫生关系：该申请将开发两种新的免疫测定法，以生物监测工作场所的MDI暴露，从而确保聚氨酯生产的充分安全，并保护美国劳动力的健康。