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Updated: Aug 8, 2025

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Complex Mixtures: Array PBPK Modeling of Jet Fuel Components.

Teresa R Sterner1,2, Tammie R Covington1,2, David R Mattie2

  • 1Henry M. Jackson Foundation for the Advancement of Military Medicine, Wright-Patterson Air Force Base, Dayton, OH 45433, USA.

Toxics
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PubMed
Summary
This summary is machine-generated.

A new physiologically-based pharmacokinetic (PBPK) model quantifies jet fuel component dosimetry. This array PBPK model accurately predicts internal tissue concentrations for complex mixture exposures, aiding in risk assessment.

Keywords:
PBPKjet fuelmixture

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Area of Science:

  • Toxicology
  • Pharmacokinetics
  • Computational Modeling

Background:

  • Jet fuels contain multiple chemical compounds.
  • Understanding the internal dosimetry of these compounds is crucial for assessing health risks, particularly ototoxicity.
  • Existing models often focus on single chemicals, limiting simultaneous assessment of mixtures.

Purpose of the Study:

  • To develop and validate an array physiologically-based pharmacokinetic (PBPK) model for simultaneous dosimetry of jet fuel components.
  • To predict internal tissue concentrations in rats following inhalation exposure to jet fuel components.
  • To compare tissue kinetics between different jet fuel formulations.

Main Methods:

  • An array PBPK model was developed to simulate inhalation exposures to toluene, ethylbenzene, xylenes, n-nonane, n-decane, and naphthalene.
  • The model incorporates lung and liver metabolism and tissue kinetics, including the cochlea and auditory brain regions.
  • Model predictions were validated against published rat studies and applied to predict kinetics for specific jet fuel exposures.

Main Results:

  • The array PBPK model successfully simulated blood and tissue dosimetry data from single-chemical rat studies.
  • The model predicted tissue kinetics for a jet fuel hearing loss study.
  • Simulations compared rat tissue kinetics for JP-8 and a Virent Synthesized Aromatic Kerosene (SAK):JP-8 blend.

Conclusions:

  • The array PBPK model is a valuable tool for simultaneously quantifying the dosimetry of multiple jet fuel components.
  • This approach aids in comparing potential tissue burdens from complex mixture exposures.
  • The model supports risk assessment for occupational exposures to jet fuels.