نبذة مختصرة : The single largest source of chemical exposure on military bases of the North Atlantic Treaty Organization (NATO) is jet propulsion fuel 8 (JP-8), which is the preferred fuel for both aircraft and military vehicles in NATO countries. JP-8 comprises many aromatic hydrocarbons, including benzene and naphthalene, and aliphatic hydrocarbons such as nonane and decane (McDougal et al. 2000). Exposures to JP-8 can occur during spills, transportation and storage of the fuel, as well as during fueling, general maintenance and operation of aircraft and military vehicles, fueling of military tent heaters, and cleaning and degreasing of parts with the fuel. Since JP-8 can enter the body via both inhalation and dermal contact, the assessment of occupational exposures to fuel constituents can be difficult. Personal sampling of JP-8 vapors provides information about inhalable levels but not about dermal exposure levels. Similarly, sampling the exposed skin provides information about dermal but not about inhalable levels. Conversely, the collection of end-exhaled breath concentrations provides an integrated estimate of uptake via both inhalation and dermal contact (Egeghy et al. 2003; Pleil et al. 2000) but cannot determine the relative contributions of the two exposure routes to the internal dose. Through statistical evaluation of levels of naphthalene in air, breath, and skin, measured in the U.S. Air Force personnel during fuel maintenance procedures, both inhalation and dermal exposures to JP-8 were demonstrated to contribute to the internal dose (Chao et al. 2006). However, because of the respiratory protection used in that population, it was difficult to determine the relative contributions of dermal and inhalation exposures to the systemic levels of JP-8 components. Physiologically based toxicokinetic (PBTK) modeling is an effective tool for quantifying the absorption, distribution, metabolism, and elimination of chemicals. PBTK models have been developed for various components of JP-8, notably naphthalene and decane (Perleberg et al. 2004; Quick and Shuler 1999; Willems et al. 2001). The model developed by Quick and Shuler (1999) focused on the disposition of naphthalene in five compartments representing the lungs, liver, fat, rapidly perfused tissues, and slowly perfused tissues and relied on in vitro data to calibrate kinetic constants. Willems et al. (2001) refined the Quick and Shuler (1999) model by using kinetic constants derived from in vivo data from laboratory animal experiments performed by the National Toxicology Program. They observed that a diffusion-limited PBTK model was necessary to characterize the toxicokinetic behavior of naphthalene in rats and mice. Perleberg et al. (2004) developed a PBTK model using decane as a chemical marker of JP-8. Data for calibration and validation of this model were derived from an animal study in which rats were exposed for 4 hr to decane vapor at three different concentrations (1,200, 781, or 273 ppm). Their final model consisted of flow-limited compartments for liver and lung, and diffusion-limited compartments for brain, bone marrow, fat, skin, and spleen. The model predicted the time course of decane in tissue and blood from low-level exposures to decane vapor. Because the PBTK models mentioned above did not examine the uptake via skin, we developed a PBTK model that included both inhalation and dermal routes of exposure. Naphthalene was chosen as the surrogate for JP-8 exposure because it is abundant in JP-8, is readily absorbed into blood, and is only a minor component in confounding sources of exposure such as cigarette smoke and gasoline exhaust (Rustemeier et al. 2002; Serdar et al. 2003). We expanded on the structure of a data-based compartmental model that was used to quantify the absorption, distribution, and elimination of jet fuel components (Kim et al. 2006b). Data from a study of controlled dermal exposure in humans were used to optimize the parameters in the PBTK model (Kim et al. 2006a). The optimal PBTK model, combined with exposure and biomarker data from field studies (Chao et al. 2005; Egeghy et al. 2003), was used to quantify the relative contributions of dermal and inhalation exposures to end-exhaled breath concentrations of naphthalene among U.S. Air Force personnel.
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