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Final Progress Reports: University of North Carolina-Chapel Hill: Comparative Toxicogenomics and Individual Differences in the Human Response to Dermal Exposure to Polycyclic Aromatic Hydrocarbons

Superfund Research Program

Comparative Toxicogenomics and Individual Differences in the Human Response to Dermal Exposure to Polycyclic Aromatic Hydrocarbons

Project Leader: Leena A. Nylander-French
Grant Number: P42ES005948
Funding Period: 2000 - 2011

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Final Progress Reports

Year:   2005 

This project focuses on the contribution of dermal exposure to naphthalene and benzene at potential exposed sites to total individual exposure. By determining the correlation between measured dermal exposure from tape-strip samples of the epidermis with breathing zone, measured breath, and urine concentrations in populations exposed to jet fuel (JP-8), Dr. Nylander-French and her team of researchers tested the hypothesis that dermal exposure is a significant source of total body exposure. Their results show that dermal exposure to naphthalene (as a marker for JP-8 exposure) was significantly different between the job tasks (P < 0.0001), thus reflecting the actual exposure scenarios. Furthermore, dermal exposure to JP-8 was observed to be significantly correlated with naphthalene concentration in breath and naphthalene-based metabolites (1- and 2-naphthol) in urine. Using multiple linear regression models, the team also investigated the contribution of dermal and inhalation exposure to the levels of urinary naphthols. End-exhaled breath naphthalene measured immediately after the end of work was investigated as a potential inhalation marker. For urinary 1-naphthol, breath naphthalene and smoking were the only significant predictors, explaining 87.2% and 12.8% of total variance, respectively. For urinary 2-naphthol, dermal and breath naphthalene, as well as smoking, were significant predictors, explaining 32.3%, 52.9%, and 14.8% of total variance, respectively. These results indicates that the skin provides an important route for JP-8 exposure and that dermal exposure contributes significantly to the urinary naphthalene metabolite levels and total body burden in this exposed population. Furthermore, this study clearly demonstrated, in an occupational exposure setting, the efficiency and suitability of the tape-strip technique for the assessment of dermal exposure to JP-8 and that naphthalene can serve as a useful marker of exposure and uptake of JP-8. The unexpected and intriguing finding indicating an increased contribution of dermal exposure to urinary 2-naphthol level compared to 1-naphthol level warrants further investigation for a potential role of the epidermis in naphthalene metabolism.

The project investigators are expanding their investigation to understand the toxicokinetics of human dermal exposure to naphthalene. A physiologically based pharmacokinetic (PBPK) model of exposure to JP-8 that incorporates inhalation and dermal uptake has been developed. Experimental human data have been collected to validate the model. The PBPK model will be (1) re-examined and parameters reset in an iterative process to best fit the experimental data and (2) further validated using exposure data collected on an occupationally exposed population, i.e., the U.S. Air Force personnel.

The researchers are also developing an enzyme-linked immunosorbent assay (ELISA) for quantification of benzene and naphthalene exposure in the skin. The assay uses the affinity-purified IgG fraction of the raw polyclonal antisera for identification and quantification of aryl cysteinyl keratin-1 and keratin-10 protein adducts of benzene oxide and naphthalene-1,2-oxide (antigens) isolated from the top cell layers of the non-viable squamous epithelium (stratum corneum). These antibodies are currently used to develop an ELISA to measure adducts extracted from dermal tape-strip samples collected from persons occupationally exposed to naphthalene and benzene.

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