A PBPK modeling assessment of the competitive metabolic interactions of JP-8 vapor with two constituents, m-xylene and ethylbenzene.
Jet Propellant 8 (JP-8) is a kerosene-based jet fuel used in the military and is composed of hundreds of hydrocarbons. A PBPK model was developed to assess the metabolic interactions of JP-8 vapor on two prominent constituents of JP-8 vapor, m-xylene (XYL) and ethylbenzene (EBZ). A limited number of rats were exposed to JP-8 vapor in a Leach chamber for 4 h to 380, 1100, or 2700 mg/m3 (total hydrocarbon). Several individual hydrocarbons were monitored in the chamber atmosphere, including XYL, EBZ, and the total hydrocarbon concentration. Blood and liver were harvested and analyzed by a novel headspace SPME/GC-MS method that allowed for identification of individual hydrocarbons and low limits of detection. The PBPK model was able to describe the metabolic interactions between XYL, EBZ, and a lumped aromatic fraction of JP-8 vapor estimated to be 18 to 25% of the fuel vapor. Competitive inhibition of XYL and EBZ metabolism was observed for JP-8 vapor inhalation exposures of 1100 and 2700 mg/m3. Future inhalation studies with jet fuel include aerosol exposures and expansion of the PBPK models to include other hydrocarbons such as n-alkanes and upper respiratory tract dosimetry of aerosol droplets.
Campbell
Jerry L
JL
Environmental Health Science Department, College of Public Health, University of Georgia, Athens, Georgia, USA.
Fisher
Jeffrey W
JW
D000336:Aerosols; D000818:Animals; D001555:Benzene Derivatives / Q000493:pharmacokinetics*; D006838:Hydrocarbons / Q000493:pharmacokinetics*; D019570:Inhalation Exposure; D008297:Male; D008954:Models, Biological; D051381:Rats; D011916:Rats, Inbred F344; D014835:Volatilization; D014992:Xylenes / Q000493:pharmacokinetics*
D000336:Aerosols; D001555:Benzene Derivatives; D006838:Hydrocarbons; C098607:JP8 aviation fuel; D014992:Xylenes; C004912:ethylbenzene; C031285:3-xylene