PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene.
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.
Kim
David
D
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.
Andersen
Melvin E
ME
Chao
Yi-Chun E
YC
Egeghy
Peter P
PP
Rappaport
Stephen M
SM
Nylander-French
Leena A
LA
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
D000395:Air Pollutants, Occupational; D006838:Hydrocarbons; C098607:JP8 aviation fuel; D009281:Naphthalenes; C031721:naphthalene