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Permissible Exposure Levels for Selected Military Fuel Vapors
GENERAL DETERMINANTS OF HYDROCARBON TOXICOKINETICS
Because of the great diversity in the biochemical and physical properties of the numerous volatile organic chemicals (VOCs) found in JP-5, JP-8, and DFM, it is useful to examine, in a general way, the factors important for uptake, distribution, metabolism, and elimination of hydrocarbons. Dispositional determinants include, but are not limited to, those of a physiological nature, such as alveolar ventilation, cardiac output, blood flow to organs, and organ volumes. Chemical determinants of disposition include partition coefficients, which describe the distribution of the VOC between blood and air or between blood and tissue at equilibrium. Metabolic determinants, including the capacity for metabolism and the enzyme affinity for the hydrocarbon, are critical in regulating the disposition of VOCs. Binding of the hydrocarbon or metabolite to tissue macromolecules might also be important because, in some cases, binding to a critical macromolecule determines toxicity. Determinants for metabolism or binding can be modified by the exposure history of an individual, resulting in either inhibition or induction of metabolism or binding. Alternatively, toxicoldnetic determinants can be modified by simultaneous exposure to other hydrocarbons. Because JP-5, JP-8, and DFM are complex mixtures of VOCs, it is most likely that this final factor, simultaneous exposure to other VOCs, is the most important determinant in understanding hydrocarbon disposition following inhalation of these mixtures.
Partitioning of VOCs between biological media is a key chemical factor in describing and predicting disposition and tissue dosimetry of hydrocarbons. Partition coefficients are a measure of the affinity of the VOC for one medium compared with another at equilibrium. Partition coefficients for VOCs are often measured in vitro by using methods such as the vial-equilibration method (Gargas et al., 1989). Partition coefficients for some of