Parallel Dermal Subcompartments for Modeling Chemical Absorption

Abstract

Understanding the absorption of chemicals through the skin is of importance to many fields of study. Biologically-based models can be used to simulate the absorption process and predict the rate of absorption and the amount of the chemical in various parts of the body and skin. When these models consist of physiological and biochemical parameters that can be measured, they can be extremely useful. When a model is appropriately validated, the results can be extrapolated across species to predict the effect of human exposure. In this paper we develop two new physiologically-based pharmacokinetic (PBPK) models which predict the concentration of Dibromomethane in the blood of rats after dermal vapor exposure. These two new models expand a previously developed homogeneous skin model by adding parallel skin subcompartments to represent skin appendages and layered subcompartments to represent the distinct layers of the skin. The predictions of these new models match the experimental data better than the original homogeneous model, as well as being more physiologically descriptive. Sensitivity analysis showed us which parameters were the most sensitive to change and thus revealing the parameters we should be most concerned with measuring. After being properly validated, these models could be a great improvement over previous models in the ability to extrapolate results for different species, doses, and durations.

Key Words:

• Pharmacokinetic modeling
• percutaneous absorption
• dermal subcompartments
• sensitivity analysis
• permeability constants