Assessment of dermal exposure to benzene & napthalene

皮肤暴露于可能直接或间接（通过亲电代谢物）与皮肤相互作用的致敏性和致癌性物质中，人们对其了解和研究甚少。我们对这一研究领域的理解和发展的一个主要限制是缺乏非侵入性设备和/或相关方法来确定化学特异性皮肤暴露。需要新的方法来确定在环境和职业暴露条件下诱发不良反应的阈值剂量。我们建议测试的假设，非常低水平的皮肤暴露于苯和萘可以直接检测使用胶带剥离去除角质表皮样品。随后取出取出的上皮，然后用分析化学试剂分析最近暴露的苯或萘。酶联免疫吸附测定（ELISA）方法可用于定量蛋白质加合物作为低水平慢性暴露的生物标志物以及皮肤和全身暴露的相关性。首先，我们将开发并使用一种非侵入性胶带剥离技术，结合分析化学方法来测量两个选定的工人群体的皮肤暴露于苯和萘。其次，我们将调查这些暴露人群中接触苯和萘系统的皮肤暴露之间的潜在关系。最后，我们将开发一种ELISA方法，利用苯代谢产物蛋白加合物产生的多克隆抗体来定量皮肤对苯的暴露。苯被细胞色素P450 CYP2E1代谢为苯氧化物和其他亲电物质，可用于测量角蛋白内聚（皮肤暴露）和人血清白蛋白（全身暴露）。这些拟议的研究获得的结果将增加我们对皮肤暴露的重要性和作用以及皮肤和内部组织所接受的内剂量的认识。此外，可以检查皮肤暴露可能导致的潜在健康影响（过敏性接触性皮炎、癌症等）和相关暴露。最终，本研究中开发的程序和方法可作为非侵入性皮肤采样程序的模型，可靠且可重复地确定皮肤暴露于环境毒物。通过可靠的接触评估，可以制定和执行尽量减少接触、从而防止不良健康影响的战略。

Dermal exposure to allergenic and carcinogenic agents that may interact directly or indirectly (via electrophilic metabolites) with the skin is poorly understood and investigated. A major limitation to our understanding and development of this area of research has been the absence of non-invasive device and/or associated methodology to determine chemical specific skin exposure. New methods to determine the threshold dose to induce adverse effects under environmental and occupational exposure conditions are needed. We propose to test the hypothesis that very low levels of dermal exposure to benzene and naphthalene can be directly detected using samples of the keratinized epidermis removed by tape stripping. Subsequent extraction of the epithelium removed may then be analyzed for benzene or naphthalene by analytical chemical for recent exposures. Enzyme-linked immunosorbent assay (ELISA) methods may be used for quantification for protein adducts as biomarkers for low level chronic exposures and for correlation of dermal and systemic exposure. First, we will develop and use a non-invasive tape-stripping technique coupled with analytical chemistry methods to measure dermal exposure to benzene and naphthalene in two selected populations of workers. Secondly, we will investigate the potential relationship between dermal exposure in systems exposure to benzene and naphtalene in these exposed populations. Finally, we will develop an ELISA method for quantification of dermal exposure to benzene using polyclonal antibodies produced to protein adducts of benzene metabolites. Benzene is metabolized by cytochrome P450 CYP2E1 to benzene oxide and other electrophilic species, which may be used for measuring adduction to keratin (dermal exposure) to human serum albumin (systemic exposure). The results obtained by these proposed studies will increase our knowledge of the significance and the role of dermal exposure and the internal dose received to both the skin and internal tissues. In addition, the potential health effects (allergic contact dermatitis, cancer, etc.) that may result due to dermal exposure can be examined and correlated exposures. Ultimately, the procedures and methods developed in this study may be used as a as a model non-invasive skin-sampling procedure that reliably and reproducibly determines dermal exposure to environmental toxicants. Through reliable exposure assessment, strategies for minimizing exposure and, thus, preventing adverse health effects, can be developed and implemented.