302 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS o o o x z o -- 200- 100: s MOUSE 100: 1 1 0 i ,b o 100: 100: 10' ._•'•RRY RAT 10' •MOUS 100: 1500- 1000: J i lOO ,,// SILASTIC MEMBRA 80 urn ,ol , 0 5 10 0 5 1•3 ALKYL CHAIN LENGTH Figure 2. In vitro permeability profile of n-alkanols through various animal skins, human skin and Si- lastic © membrane.

NUDE RAT SKIN PERMEABILITY 303 Table II The Alkyl Chain Length Sensitivity (w-Value) for the In Vitro Permeation of n-Alkanols Through Human Skin, Skins of Various Animals, and Silastic © Membrane Membrane w-Values Reference Human 0.30 1 Hairless Mouse 0.32 2 Nude Rat 0.26 Present Study Fuzzy Rat 0.26 4, 5 Swiss Mouse 0.15 6 Furry Rat 0.15 7 Silastic © Membrane 0.26 8 gence of the second plateau. Usually all three permeability mechanisms are operative for all permeants however, only one mechanism will predominate. In vitro skin permeation studies can be done using either synthetic or biological mem- branes. Synthetic membranes such as Silastic © do not exhibit the three pathways dis- cussed above. In Figure 2 (Silastic © membrane) there is no lower plateau, indicating an absence of the pore-type transport pathway. This can be explained by the fact that Silastic © membrane does not contain the anatomical pore-type pathways which are present in the skin. The upper plateau seen in this figure represents a different mecha- nism from that discussed for biological membranes. Permeation in this region of the curve is "aqueous boundary layer controlled." This means that the transport of highly non-polar molecules is mainly limited by the stagnant layer of water (the unstirred layer) which is present adjacent to the Silastic © membrane in the diffusion cell. Thus, any further increase in permeant lipophilicity does not result in increased P-values. In fact, the P-values should decrease slightly because diffusivity is inversely proportional to the molar volume of the permeant and the transport of increasingly more lipophilic compounds through an aqueous layer would gradually decrease. From these discussions, it appears that only the lipophilic pathway is common to both skin and Silastic ©. Therefore, Silastic © membrane would not appear to be a good substitute for skin in permeation studies. However, it serves a useful purpose in providing mechanistic in- sight into permeation processes by differentiating the biological effects from the ther- modynamic influences. Evaluation of the acceptability of an animal model is based primarily on the alkyl chain-length profile (i.e., shape of the curve) and the partitioning dependency of per- meation (q'r-value). The curves for the animal models (Figures 1 and 2) are generally sigmoidal and appear comparable to the curve for human skin. No data are available for alkanols higher than hexanol for the furry rat however, with additional data this curve should also plateau. Differences begin to appear among the animal models when the q'r-values are compared (Table II). The furry species (Swiss mouse and furry rat) have q'r-values which are significantly lower than the other animal models, indicating that lipoidal transport is significantly different in furry species than in hairless or fuzzy species (nude and fuzzy rats). Since human skin has very little hair (certain hairy regions excluded), it might be expected that hairless animals would provide permeation data which are better correlat-