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ToxSci Advance Access published online on June 26, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl048
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received February 27, 2006
Accepted June 16, 2006

Biotransformation and Toxicokinetics

A Dermatotoxicokinetic Model of Human Exposures to Jet Fuel

David Kim 1, Melvin E. Andersen 2, and Leena A. Nylander-French 1 *

1 Department of Environmental Sciences and Engineering, School of Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7431
2 CIIT Centers for Health Research, 6 Davis Drive P.O. Box 12137, Research Triangle Park, NC 27709-2137

* To whom correspondence should be addressed.
Leena A. Nylander-French, E-mail: leena_french{at}unc.edu


  Abstract

Workers, both in the military and the commercial airline industry, are exposed to jet fuel by inhalation and dermal contact. We present a dermatotoxicokinetic (DTK) model that quantifies the absorption, distribution, and elimination of aromatic and aliphatic components of jet fuel following dermal exposures in humans. Kinetic data were obtained from 10 healthy volunteers following a single dose of JP-8 to the forearm over a surface area of 20 cm2. Blood samples were taken before exposure (t = 0 h), after exposure (t = 0.5 h), and every 0.5 h for up to 3.5 h post-exposure. The DTK model that best fit the data included five compartments: (1) surface, (2) stratum corneum, (3) viable epidermis, (4) blood, and (5) storage. The DTK model was used to predict blood concentrations of the components of JP-8 based on dermal exposure measurements made in occupational exposure settings in order to better understand the toxicokinetic behavior of these compounds. Monte Carlo simulations of dermal exposure and cumulative internal dose demonstrated no overlap among the low-, medium-, and high-exposure groups. The DTK model provides a quantitative understanding of the relationship between the mass of JP-8 components in the stratum corneum and the concentrations of each component in the systemic circulation. The model may be used for the development of a toxicokinetic modeling strategy for multi-route exposure to jet fuel.

Keywords: toxicokinetics; skin; exposure assessment; jet fuel.

The authors certify that all research involving human subjects was done under full compliance with all government policies and the Helsinki Declaration.


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