title: PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene.
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 x 10(-5) cm/hr, b) permeability coefficient for the viable epidermis 3.0 x 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.
authors.affiliation: Department of Environmental Sciences and Engineering, School of Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7431, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kim
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Andersen
authors.forename: Yi-Chun E
authors.initials: YC
authors.lastname: Chao
authors.forename: Peter P
authors.initials: PP
authors.lastname: Egeghy
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Rappaport
authors.forename: Leena A
authors.initials: LA
authors.lastname: Nylander-French
mesh_terms: D000395:Air Pollutants, Occupational / Q000032:analysis* / Q000378:metabolism; D001944:Breath Tests; D005260:Female; D006801:Humans; D006838:Hydrocarbons / Q000737:chemistry*; D019570:Inhalation Exposure; D008297:Male; D008889:Military Personnel; D008954:Models, Biological; D009281:Naphthalenes / Q000032:analysis / Q000493:pharmacokinetics*; D016273:Occupational Exposure; D010539:Permeability; D012869:Skin Absorption / Q000502:physiology*; D013997:Time Factors; D014481:United States
chemical_list: D000395:Air Pollutants, Occupational; D006838:Hydrocarbons; C098607:JP8 aviation fuel; D009281:Naphthalenes; C031721:naphthalene