| PBTK Modeling Demonstrates Contribution of Dermal and Inhalation Exposure Components to End-Exhaled Breath Concentrations of Naphthalene David Kim,1 Melvin E. Andersen,2 Yi-Chun E. Chao,1 Peter P. Egeghy,1* Stephen M. Rappaport,1 and Leena A. Nylander-French1 1Department of Environmental Sciences and Engineering, School of Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 2CIIT Centers for Health Research, Research Triangle Park, North Carolina, USA Abstract
Background: Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Objective: Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. Methods: The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. Results: The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8  10–5 cm/hr, b) permeability coefficient for the viable epidermis 3.0 10–3 cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers' exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%) . Conclusions: PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures. Key words: dermal, exposure assessment, inhalation, jet fuel, naphthalene, physiologically based toxicokinetic model. Environ Health Perspect 115:894–901 (2007) . doi:10.1289/ehp.9778 available via http://dx.doi.org/ [Online 14 February 2007]
Address correspondence to L.A. Nylander-French, Department of Environmental Sciences and Engineering, School of Public Health, The University of North Carolina at Chapel Hill, CB #7431, Rosenau Hall, Chapel Hill, NC 27599-7431 USA. Telephone: (919) 966-3826. Fax: (919) 966-4711. E-mail: leena_french@unc.edu *Current affiliation: National Exposure Research Laboratory, Human Exposure and Atmospheric Sciences Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA. We express special thanks to D. Leith and J. Pleil for constructive comments and to L. Ball for allowing the use of her laboratory for the dermal exposure study. We also acknowledge S. Waidyanatha for her assistance with the chemical analysis. This study was supported by National Institute of Environmental Health Sciences grants P42-ES05948 and T32-ES07018, by the U.S. Air Force through subcontract 1331/0489-01 with Texas Tech University, and by National Institute for Occupational Safety and Health grant T42/CCT410423-09. The authors declare they have no competing financial interests. Received 2 October 2006 ; accepted 14 February 2007.
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