ABSTRACT
Cutaneous penetration studies in human volunteers are hampered due to the complexity of xenobiotic toxicokinetics and metabolism in vivo and due to the ethical problems associated with possible undesirable effects of the chemical under investigation. The use of animal species, such as hairless mice, 1 human skin grafted nude mice, 2 hairless rats, 3 or dogs, 4 is equally cumbersome and also has the disadvantage that species differences in metabolism, elimination, etc. prevent extrapolation of the results to humans. 5 6
In vitro, the diffusion cell technique using human skin is most widely used to measure skin
penetration. However, this method has some major disadvantages: (a) Only the epidermis and the upper part of the dermis are used; effects of the investigated chemicals on the dermal vascular system are ignored; 7 (b) the rate of penetration is grossly affected by the composition of the recipient medium, usually a buffer containing organic solvents, such as ethanol; 8 and (c) the flow at which the medium moves along the inner surface of the skin piece is usually arbitrarily chosen. Different flow rates have substantial effect on the amount of substance that is measured in the medium.
