Toxicokinetics

Given that gasoline, kerosene, diesel, JP-4, JP-5, and JP-8 are composed of hundreds of hydrocarbon compounds, it is impractical to describe here the toxicokinetics of each component. Because fuels contain many different components, they will exhibit a wide range of variability regarding absorption, metabolism, and excretion. General aspects of the toxicokinetics of JP-8 were presented in the recent National Research Council report Toxicologic Assessment of Jet-Propulsion Fuel 8 (NRC 2003). The principles are applicable to gasoline, kerosene, diesel, JP-4, and JP-5, and they are repeated here. The major determinants of hydrocarbon toxicokinetics after systemic uptake are disposition-related physiologic properties of the organism—such as alveolar ventilation, cardiac output and blood flow to the organs, and organ volume—and partition coefficients of the fuel components. Hydrocarbons with high blood:air partition coefficients are absorbed to a greater extent than compounds with poor blood solubility. Given that most hydrocarbons have fairly high fat:air and fat:blood partition coefficients, it is not surprising that fat or adipose tissue is a major storage depot for many of the fuel components. For hydrocarbons with high fat:blood partition coefficients, metabolic clearance after cessation of exposure is especially important. Hydrocarbons and their metabolites accumulate in lipid-rich tissues, so the absence of hydrocarbons and their metabolites in exhaled air, blood, or urine does not necessarily mean the absence of systemic exposure. Cytochrome P450 enzymes metabolize most hydrocarbons by such reactions as aliphatic hydroxylation, aromatic hydroxylation, and epoxidation. Alcohol and aldehyde dehydrogenases play an important role in metabolizing alcohols into their corresponding keto acids. Phase II reactions—including conjugation with glutathione, glucuronic acid, sulfate, and glycine—are important in formation of water-soluble metabolites.

Data on absorption, distribution, metabolism, and elimination of gasoline, kerosene, diesel, JP-4, JP-5, and JP-8 are sparse. The components of each of these fuels are processed primarily according to their own physicochemical properties. When Tsujino et al. (2002) applied 1ml of kerosene dermally to the abdomen of rats for 1, 3, or 6 hr, it was absorbed and distributed via blood circulation, but the aromatic compound trimethylbenzene was absorbed by the skin to a greater degree than the aliphatic hydrocarbons. Kimura et al. (1988) had similar results with inhaled gasoline and kerosene. Local and systemic effects observed after exposure to those fuels indicated that they are absorbed by the respiratory tract, the gastrointestinal tract, and the skin. Toxicokinetic information on several fuel components is available (in particular, benzene, toluene, and xylenes); but their interactions with each other and with other hydrocarbon components may affect their toxicokinetic properties (ATSDR 1989, 1990, 1991, 1995e; NRC 1996a).

Experimental Studies

Controlled studies of the toxicity of gasoline, kerosene, diesel, JP-4, JP-5, and JP-8 in humans and laboratory animals are summarized here, with emphasis on studies that addressed whether effects persist after cessation of exposure. Epidemiologic studies of the adverse health effects of the fuels will be discussed in later chapters.



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