| Dermal exposure to Jet-Propulsion Fuel 8 (JP-8) is prevalent in the United States Air Force. Although a large amount of exposure data was generated from previous occupational studies, dermal exposure to JP-8 was poorly characterized and quantitative estimates of the contribution of dermal exposure to the internal dose of JP-8 were unavailable. To fill this data and knowledge gap, a controlled dermal exposure study was designed to quantify the toxicokinetic behavior of naphthalene, 1-methyl naphthalene, 2-methyl naphthalene, decane, undecane, and dodecane. Further, a toxicokinetic model was constructed; this model provided the basis for the development of a physiologically-based toxicokinetic (PBTK) model of dermal and inhalation exposure to JP-8. The PBTK model was used to quantify the contribution of dermal exposure to the internal dose of naphthalene. Results of this research suggest that the apparent human permeability coefficient is 10-fold lower than estimates made in vitro. Further, simulations of dermal exposure to JP-8 suggested that the tape-strip method can be used to differentiate exposure groups in epidemiology studies. The median relative contribution of dermal exposure to the internal dose of naphthalene was 1.7% (10th percentile = 0.3% and 90th percentile = 6.9%). The overall implication of these findings is that protection from dermal exposure to JP-8 can reduce the internal dose of naphthalene. However, for most of the US Air Force personnel, the major contribution to the internal dose was from inhalation exposure. The two most significant contributions to the scientific understanding of JP-8 exposures were (1) improved characterization of dermal exposures, and (2) quantitation of the toxicokinetic behavior of aromatic and aliphatic hydrocarbons. Overall, this research has presented a new direction for toxicokinetic modeling human exposures to complex chemical mixtures. This modeling strategy may be used to better assess the risks associated with JP-8 exposures in human populations. |
