Abstract for Short Course 1.3

 

 

Modelling percutaneous penetration

Annette Bunge
Colorado School of Mines, USA

Skin contact with even extremely toxic compounds is only a problem when chemical permeation across the skin is sufficient to produce an adverse health effect, either acute or chronic. As a result, the total amount and the rate of percutaneous penetration are key determinants of health risk from skin exposure to toxic chemicals. Mathematical models for predicting percutaneous penetration are needed because it is possible to experimentally study only a small fraction of the chemicals of concern. Although skin's effectiveness as a barrier arises from its unique physical and chemical structures (i.e., layers of thin, broad, almost impermeable flat plates surrounded by lipid bilayers), mass transfer models that treat skin as a pseudo-homogeneous membrane can provide useful estimates of percutaneous penetration. These models predict chemical absorption into and penetration through the skin based on chemical specific dermal absorption parameters (e.g., partition coefficients, diffusion coefficients or permeability coefficients). In turn, these dermal absorption parameters are estimated using structure-activity algorithms derived by various investigators using databases of dermal absorption measurements, almost all from aqueous solutions. Various investigators have proposed alternative mass transfer models. Significantly, these different models can produce appreciably different estimates of percutaneous penetration, even when the same dermal absorption parameters are used in the calculations. In this lecture, the causes of these differences will be described and guidelines provided for choosing mass transfer models. In addition, the use and limitations of algorithms for estimating the dermal absorption parameters will be discussed, especially with respect to predicting percutaneous penetration of chemicals that are not in aqueous solutions.

Content last modified: 14 May 2005

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