Pharmacokinetic Modeling of JP-8 Jet Fuel Components: I. Nonane and C9- C12 Aliphatic Components

摘要

Exposures to JP-8 can occur from vapor, liquid or aerosol. Inhalation and dermal are the most prevalent routes of exposure, and acute effects include neurobehavioral deficits. Occupational exposures of interest include aircraft fuel tank workers and exhaust workers. JP-8 is a complex mixture of hundreds of components including straight chain alkanes, branched chain alkanes, cycloalkanes, diaromatics and napthalenes. A first step to developing a physiologically-based pharmacokinetic (PBPK) model for JP-8 is to develop models for representative components. Nonane is a good biomarker in breath for JP-8 aliphatic exposure (fingerprint compound). Nonane is a highly lipophilic compound (log Kow = 5.65), and has been observed to distribute preferentially in brain tissue. Its behavior in the body can he described in terms of a physiologically-based pharmacokinetic (PBPK) model that includes the blood, lungs, liver, muscle, and fat. Such a model is developed on the basis of in-house rat inhalation data (with measured blood levels), and validated by applying it to published rat inhalation data (blood and brain levels). The model is used to predict body burdens of nonane under occupational exposure conditions (ambient air concentrations for fuel tank workers and aircraft attendants) and is consistent with limited occupational body burden data (exhaled breath levels).