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
|February 28, 2023
Summary
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.
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.
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