206 JOUBNAL OF THE SOCIETY OF COSMETIC CHEMISTS but there was no correlation between the type or amount of lipid extracted and the degree of alteration of the water barrier function. There are a number of agents that increase the permeability of the skin by reducing the epidermal barrier to water transpiration. All of these agents must have one common property, the ability to damage or alter the nature of the stratum eorneum in such a way that its diffusiona] resistance is reduced (6). For example, the activation energies for water through epidermal mem- branes, pretreated with a mixture of chloroform-methanol (2:1) to delipidize the membrane, range from 6.08-6.5 keal/mole (29). These values are much lower than the activation energy of approximately 15 keal/mole (20) for water penetrating normal epidermis and undoubtedly reflect substantial mem- brane damage. Solvents with both polar and lipophilie properties apparently have the feet not only of removing skin lipids but also of breaking down the complex structure of the barrier, thus making it defective and possibly subject to entry by other chemical agents which do not penetrate intact skin. Substances such as dimethylsulfoxide (DMSO), dimethylformamide (DMF), and dimethyl- aeetamide (DMA) all have the ability to produce a striking but reversible suppression ooe barrier resistance. They are all strongly hygroseopie and it is likely that the presence of these substances in the stratum eorneum increases the hydration of the tissue and therefore its permeability. DMSO has a per- meability constant of 300 /zem/min (110) as compared to a value of 45 /zero/rain for water through excised human skin (73). DMSO appears to alter the complex interrelationship of water, lipids, pro- tein, and mueopolysaeeharides regulating epidermal water barrier function (111). This may explain, in part, the sometimes observed variable role of DMSO. Swelling may induce the formation of channels within the matrix of the stratum eorneum which either favor the passage of varied compounds (112) or lower the diffusional resistance of the stratum eorneum. DMSO can extract soluble components from the stratum eorneum, suggesting ultrastruc- tural modifleations consistent with an increase in permeability. There are possible reversible eonflguration changes in skin protein structure brought about by substitution of integral water molecules by DMSO, with resultant swelling (113). A sharp increase was found in the flow rate of tritiated water through hairless mouse skin if the DMSO solutions used to pretreat the skin contained in excess of 70% DMSO. Low concentrations appear to produce little change in the skin barrier, whercas marked effects are observed in solu- tions containing 50% DMSO, or more (114). Polar, hydrogen-bonding solvents like water and DMSO are capable of re- acting with the bulk of the tissue (the protein) and not just the minor lipid component. When applied in large concentration, they become incorporated into the tissue and constitute a large percentage of the membrane substance. The membrane expansion is determined by the extent of their incorporation

WATER AND THE SKIN 207 and the accompanying reaction of the structural elements of the tissue. The membrane diffusivity appears to be determined by the stability of the re- suiting hydrogen-bonded solvent structure, for it is largely the solvent in the membrane through which difi'usion occurs. The membrane-water association is apparently much tighter than the membrane-DMSO structure and the dif- [usivity of the membranc-water mcdia is accordingly much lower (28). Soaps and detergents are perhaps the most damaging of all substances rou- tinely applied to the skin (10, 115). Treatment of isolated human or animal callus with soap or detergent solutions can reduce its ability to hold water in a hmnid atmosphere (13, 43). Dilute aqueous solutions of anionic detergents were found to increase the permeability of water through human epidermis (99, 116, 117). The capacity to damage the skin appears to be a general property of charged surfactants (9,8, 108). The presence of anionic surfactants within the skin tissues greatly reduces the amount of "bound water" as measured by de- sorption experiments (43, 59,). The differences between anionic surfactants in their effects on water binding may be explained in terms of the damage they do to the corneum cell membranes, different degrees of damage resulting in the extraction of different quantities of water-soluble substances (108). The influence of anionic surfactants may be related to their ability to in- crease the permeability of the skin to water by altering the physical state of water in the skin in such a way as to permit greater freedom to the passage of charged hydrophilic substances (89). Anionic surfactants apparently bind strongly with the protein and cause a reversible denaturation and an uncoil- ing of the filaments. This is accompanied by a gross expansion of the tissue. Water diffusion in the presence of the soap is much easier through the ex- panded and unbound water regions than in the original membrane (9,8). In actuality, the mechanism of the loss of capacity of corneum to bind water in the presence of surfactants is still not understood (10). (Received July 31, 1972) •R. EFERENCES (l) Blank, I. H., Further observations on factors which influence the water content of the stratum corneum, J. Invest. Dermatol., 9.1, 9.59 (1953). ('2) Blank, I. H., Factors which influence the water content of the stratum corneum, Ibid., 18, 433 (1959.). (3) Laden, K., Natural moisturizing factors in skin, Amer. Per/urn. Cosmet., 89., 77 (1967). (4) Gaul, L. E., Relation of dew point and barometric pressure to horny layer hydration, Proc. Sci. Sec. Toilet Goods Ass., 40, 1 (1963). (5) Gaul, L. E., and Underwood, G. B., Relation of dew point and barometric pressure to chapping of normal skin, J. Invest. Dermatol., 17, 9 ( 1951 ). (6) Katz, M., and Paulsen, B. J., Absorption of drugs through the skin, in Brodie, B. B., and Gillette, J., Handbook of Experimental Pharmacology, Springer-Verlag, Berlin, ] 971, Vol. 28.