Computational Approaches for Predicting Nonlinear Interactions of Chemical Mixtures in Biological Systems
Abstract
The overarching goal of this work was to develop a computational modeling approach for predicting uptake of inhaled hydrocarbon (HC) aerosols and vapors from petroleum-based and synthetic hydrocarbon mixtures. Using a novel approach for measurement of aerosolized HC uptake and distribution that was developed for n-tetradecane, and data collected from exposure to HC mixtures and jet fuels, physiologically-based pharmacokinetic (PBPK) models were developed for aliphatic and aromatic jet fuel constituents, or "markers." Published vapor exposure models were also modified to describe deposition and uptake of aerosols. The remaining fuel mass was divided into "lumps" of unspeciated constituents. Three lump models were constructed; an aromatic constituent lump, a mid-range aliphatic lump, and a high molecular weight aliphatic lump. Competitive inhibition of metabolism was assumed to occur with 2 of three lumps and most of the marker hydrocarbons. The PBPK fuel model can account for exposure to vapor-only and aerosol+vapor fuel atmospheres. This model is the first jet fuel model that can be used for dose response analyses and in risk assessment. Additionally, partition coefficients were determined in vitro for a series of C9 isomers found in HC mixtures, and for additional aromatics in neat or aerosolized jet fuel for use in future HC models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2009
- Accession Number
- ADA513593
Entities
People
- Jeffrey W. Fisher
- Raphael T. Tremblay
- Sheppard A. Martin
Organizations
- University of Georgia