Gogoleva, T., J. Ademola, R. Wester, and P. Magee, and H. Maibach. Relative Contribution of Human Skin Layers on Partitioning of Chemicals with Varying Lipophilicity. In Vitro Molec. Toxicol. 1998. 11(1): 15-22.

propanolol - 00525-66-6; atrazine - 01912-24-9; 8-methoxalene; salicylic acid - 00069-72-7; indoleacetic acid - 00087-51-4; 4-acetamidophenol - 00103-90-2; theophylline - 05967-84-0

The contribution of three skin layers on the partitioning of model compounds with different physicochemical properties (propranolol, atrazine, 8-methoxalene, salicylic acid, indoleacetic acid, 4-acetamidophenol, and theophylline) was investigated. Attention was given to the influence of equilibration time course, chemical concentration, and vehicle hydrophilicity/lipophilicity. Water and isopropyl myristate (IPM) were chosen as the model vehicles. The data demonstrate that lipophilic and hydrophilic compounds behave differently in the skin layers. However, the physicochemical values of the lipophilic compounds were signficantly higher in stratum corneum (SC) and epidermis (SCE) than in dermis (D). Concentration of the drug in the vehicle dictates the level of partitioning in skin layers. As the concentration of the chemicals increases, the PC values inversely decrease. The partitioning behavior of the model compounds in both vehicles was in reverse relationship with octanol/water PCs and was compatible with the physicochemical properties of the chemicals. The data assume that, while stratum corneum is considered to be the major barrier to the penetration of chemicals through human skin, epidermis and dermis also contribute to the overall partitioning of model compounds. The observations presented here may aid prediction of in vivo and in vitro transport of drugs and environmental agents through human skin.