A physiologically based mathematical model of dermal absorption in man.
A sound understanding of the mechanisms determining percutaneous absorption is necessary for toxicological risk assessment of chemicals contacting the skin. As part of a programme investigating these mechanisms we have developed a physiologically based mathematical model. The structure of the model parallels the multi-layer structure of the skin, with separate surface, stratum corneum and viable tissue layers. It simulates the effects of partitioning and diffusive transport between the sub-layers, and metabolism in the viable epidermis. In addition the model describes removal processes on the surface of the skin, including the effects of washing and desquamation, and rubbing off onto clothing. This model is applied to data on the penetration of the herbicide fluazifop-butyl through human skin in vivo and in vitro. Part of this dataset is used to estimate unknown model parameter values and the remainder is used to provide a partial validation of the model. Only a small fraction of the applied dose was absorbed through the skin; most of it was removed by washing or onto clothing. The model provides a quantitative description of these loss processes on the skin surface.
Auton
T R
TR
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Westhead
D R
DR
Woollen
B H
BH
Scott
R C
RC
Wilks
M F
MF
D000279:Administration, Cutaneous; D004817:Epidermis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008962:Models, Theoretical; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics; D012869:Skin Absorption / Q000502:physiology*
D011725:Pyridines; C050585:fluazifop-butyl