Physiologically Based Pharmacokinetic Models for the Transport of Trichloroethylene in Adipose Tissue
AIR FORCE RESEARCH LAB BROOKS AFB TX
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In this paper we present three physiologically based pharmacokinetic PBPK models for the systemic transport of trichloroethylene TCE, with a focus on the adipose, or fat tissue. TCE is a widespread environmental contaminant, and has been shown to produce toxic effects in both animals and humans. A key characteristic of TCE is its tendency to accumulate in fat tissue, which has a major impact on the overall systemic disposition of TCE. Here we use PBPK models to predict the kinetics of TCE through the various tissues and organs, including the adipose tissue. The first model utilizes the standard perfusion-limited compartmental model for the fat tissue, while the second model uses a diffusion-limited model to describe the transport through the adipose tissue. Both of these ODE models are based on well-mixed and rapid equilibrium assumptions, and do not take into account the specific and largely heterogeneous physiology of adipose tissue. The third model we discuss is a PBPK hybrid model with an axial-dispersion type model for the adipose tissue. This PDE-based model is designed to capture key physiological heterogeneities of fat tissue, including widely varying fat cell sizes, lipid distribution, and blood flow properties. Model simulations demonstrate that this model may be well-suited to predict the experimental behavior of TCE in adipose tissue using parameter estimation techniques.
- Organic Chemistry
- Statistics and Probability
- Anatomy and Physiology