XVATER AND THE SKIN 201 values of 1--10. Significant increases in water diffusion rates and decreases in water-binding capacity were observed with buffer solutions at)ove pH 10, and primarily at pH 12. These changes at high pH values can be attributed to ex- traction of water-binding substances and the solubility of keratin in the pH range 10-12. Diffusion of water through the stratum comeurn is a purely passive process affected only by physical factors as determined by ambient conditions, chiefly the water vapor pressure gradient across it (7, 8, 10, 72-77). The permeabil- ity constant of water in the skin at 25øC is approximately 0.5 x 10-acm/hr, corresponding to a flux of 0.2 mg/cm2/hr (5). The flux is approximately the same whether liquid water or saturated water vapor is applied in vitro. These data suggest that the surface concentration, which is not very different in these two instances, controls the diffusion rate and this is good evidence that water transport through skin is a passive process (10). There is little or no evidence to support specialized active transport for cells of the stratum comeurn. In order for water to move against a concentration gradient, an energy yielding "pump" is predicated in a viable epidermis. It certainly is un- likely that such a reaction would exist in a nonviable tissue like the stratum comeurn, and there is limited evidence for any transport across the stratum corneum against a concentration gradient. It appears that the major route of absorption of water during steady-state diffusion is transcellular through '%oundwater" regions in the hydrated stratum corneum (78, 79). The practi- cal and theoretical considerations involved in studying water transport through the stratum comeurn are analagous to those of studying transport through monomolecular layers (57). However, the mechanism of transport through hydrated stratum corneum may be quite different from that through normal stratum comeurn. The low diffusion constant and high activation energy obtained for water suggest that extensive hydration does not dras- tically affect the "barrier" function of the stratum comeurn (20). The more important point to consider is the thermodynamic activity of water in the barrier phase, not just the amount there. WATER BINDING The normal appearance of skin and its ability to resist environmental irri- tants, both physical and chemical, are attributable to a large degree to the capacity of the corneum layer to bind water (13). The stratum corneum has a natural ability to hold a certain amount of water against the diffusion gra- dient created by adverse ahnospheric conditions such as low dew points (7, 44). Most of our information on water-binding results from interpretation of solvent extraction of the skin. Little change occurs in either the water-bind- ing capacity in a humid atmosphere or in the weight of human callus when it is extracted with water or with polar lipid solvents such as pyridine. How-

g0g JOUBNAL OF THE SOCIETY OF COSMETIC CHEMISTS ever, there is a significant decrease in both .the weight and the water-binding capacity when callus is extracted with water after the solvent treatment al- though the callus can still hold considerable quantities of water (1). The loss in weight is due to the extraction of a water-soluble fraction which markedly enhances the ability of the stratum corneum to hold water. The corncure con- tains about 25% of its dry weight of these water-soluble substances (11, 80, 81). It seems well established that much of the water-binding capacity of corncure is due to the presence of these hygroscopic water-soluble substances and that they are in some way protected by a lipid material which must be removed with solvents before they can be extracted by water (13, 24, 44, 49, 80-87). There is no apparent correlation between the loss of water barrier capacity ooe the skin and the total amount ooe lipid extracted from the skin by the varied solvents (88). Lipid solvents appear to have very little effect on the structural elements of the stratum eorneum. Neither the mechanical strength is changed nor is any change detectable in the birefringence after lipid extraction. On the other hand, large amounts of lipid material are removed and open mem- brane interstices are apparently formed which act as low energy diffusion pathways. The lower activation energy for diffusion and nonselective higher permeability for all solutes indicates liquid-like transport through these sol- vent-filled interstices. The capacity of the tissue to bind large amounts of water is also destroyed by treatment with delipidizing solvents. This suggests that the lipid material does not simply plug the interstices in the membrane but rather aids in stabilizing the water structure in concert with the other tis- sue components (28). The degree of alteration of water barrier capacity varies greatly among different specimens of skin extracted by the same lipid solvent for the same period of time (15). Water transmission was measured through isolated hu- man, rabbit, fish, and frog skins (89). The rate of transmission was much greater for fish and frog skin. Human and rabbit skins contain a hexane-solu- ble lipid which appears to be the maior regulator of passive water holding. This hexane-extractable lipid was not detected in the fish or frog skin. Burned mammalian skin contained 30% or less of the normal water-holding lipid and transmitted up to 4 times more water than intact skin. Water transmission by the skin surfaces was inversely proportional to the water-holding lipid content of the surface. The effect of relative humidity on water binding and extensibility indicates a close relationship between the two. It is interesting to note, however, that it is that fraction of the water which is held by the water-soluble substances which is responsible for most of the extensibility. Removal of the water-sol- uble substances with ether followed by water extraction results in a very large reduction in extensibility while there is only a comparatively small reduction in the water-binding capacity. The residual water which is bound by the sol-