US EPA

3698764 

Book/Book Chapter 

Distributed Parameter Estimation of Dermal Absorption of Chemicals using a Physiologically Inspired Boundary Conditions 

Simon, L 

2009 

Human Anatomy and Physiology 

171-192 

WOS:000276093000009 

A spatial-temporal framework representing dermal absorption of chemicals is important for toxicological risk assessment. Failure to adequately estimate the amount of chemicals entering the body through the skin may compromise the ability of physiologically-based pharmacokinetic (PBPK) models to predict concentration-time profiles in individual tissue compartments. This contribution considers the conventional PBPK model equations as a boundary condition to a diffusive mass transport problem. The partial differential equation (PDE), representing the uptake of dibromomethane (500 to 10000 ppm) in the skin, is discretized into ordinary differential equations (ODEs) by orthogonal collocation techniques. The resulting system is solved in the Mathematica (R) environment to evaluate the fate of dibromomethane in the liver, fat, rapidly and slowly perfused compartments and to monitor its evolution in the different layers of the skin. This approach, which uses published physicochemical properties, predicts laboratory data very well. Cumulative amounts of dibromomethane into and out of the skin are also computed and compared to those obtained by applying a perfect sink boundary condition at the skin-capillary interface. Discrepancies between the two model predictions become more pronounced with increased exposure time. The steady-state dibromomethane concentration and the time to reach equilibrium values increased with the exposure level and stratum corneum depth. The proposed methodology may help to explore and elucidate potential links among exposure-time, concentration, skin depth and the onset of skin irritation.