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.
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