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和致癌物质的了解和调查很少。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定皮肤暴露。需要新的方法来确定在环境和职业暴露条件下引起不良反应的阈值剂量。我们建议使用胶带剥离去除角化的表皮样本来检验这一假设，即可以直接检测到非常低水平的苯和萘的皮肤暴露。随后提取的上皮细胞可以用分析化学方法分析是否有苯或萘，以确定最近的暴露情况。酶联免疫吸附试验(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，并用于皮肤和全身暴露的相关性。首先，我们将开发和使用一种非侵入性的胶带剥离技术，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，我们将调查在这些暴露人群中，暴露在苯和萘系统中的皮肤暴露之间的潜在关系。最后，我们将开发一种使用对苯代谢产物蛋白加合物产生的多克隆抗体来定量皮肤苯暴露的ELISA法。苯被细胞色素P450代谢为苯氧化物和其他亲电物种，可用于测量角蛋白(皮肤暴露)与人血清白蛋白(全身暴露)的加合作用。这些拟议研究的结果将增加我们对皮肤暴露的意义和作用的认识，以及皮肤和内部组织接受的内部剂量。此外，潜在的健康影响(过敏性接触性皮炎、癌症等)这可能是由于皮肤暴露造成的，可以进行检查并与暴露相关。最终，这项研究中开发的程序和方法可能被用作一种模型非侵入性皮肤采样程序，可靠且可重复性地确定皮肤暴露于环境毒物。通过可靠的暴露评估，可以制定和实施最大限度地减少暴露的战略，从而防止对健康的不利影响。

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.