of hydrocarbons and their metabolites in exhaled air, blood, or urine does not necessarily mean the absence of systemic exposure. With regard to metabolism, cytochrome P450 (CYP450) enzymes metabolize most hydrocarbons by such reactions as aliphatic hydroxylation, aromatic hydroxylation, and epoxidation. For many hydrocarbons, alcohol and aldehyde dehydrogenases play an important role in metabolizing alcohols to their corresponding keto acids. Phase II reactions, including conjugation with glutathione, glucuronic acid, sulfate, and glycine, are important in formation of water-soluble metabolites. The following discussion of toxicokinetics will be limited to a brief summary of disposition of only toxicologically relevant components of JP-8.
Benzene is a minor component of JP-8 (<1%), but its high volatility, its flammability, and its moderate water solubility make it an important component of JP-8 exposure (ACGIH 1996; Paustenbach 2000). Benzene is a potent genotoxicant and a recognized human carcinogen. Dose-dependent bone-marrow suppression, pancytopenia (e.g., aplastic anemia), and neurologic toxicities can occur after high-dose benzene exposure (Evans et al. 1981; McConnell 1993). The metabolism of benzene has been discussed in a previous NRC report (NRC 1996) and by ACGIH (1996). Benzene is metabolized primarily via the hepatic CYP450 system to benzene oxide, which is biotransformed to 1,2-dihydrodiol, which leads to catechol formation. Benzene oxide can also rearrange nonenzymatically to phenol, which is biotransformed to hydroquinone and benzoquinone. The water-soluble metabolites of benzene (phase II conjugative metabolism) are readily excreted (Paustenbach et al. 1993). Combined exposure to catechol and hydroquinone metabolites has been implicated in benzene’s genotoxicity (Robertson et al. 1991). Benzene and its metabolites have been shown to accumulate in humans (e.g., they appear in exhaled air and urine) after repeated exposure to benzene.
The alkylbenzenes (single-ring aromatic compounds with single or multiple aliphatic side chains) are constituents of JP-8. Toluene (methylbenzene) and mixed xylenes (o-, m-, and p-) are present in JP-8 and have been identified as potential neurotoxic chemicals after sufficiently high intentional, accidental, or occupational exposures (Gamberale and Hultengren 1972; Boor and Hurtig 1977; Klaucke et al. 1982; Hipolito 1980).