118 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS the application of water, whereas the pharmaceutical chemist is concerned with persorption which indicates passage of material into the deeper sections of the dermis and possibly into the lymph or blood systems. In fact the cosmetic chemist may not desire to have the lower layers of the skin affected. Penetration of the stratum corneum by detergents to the area of living cells may be a major factor in the severity of some eczemas. Protective creams have been devised to prevent such penetration (6). Penetration of the skin may be by solid matter causing trauma, or by energy such as heat and x-radiation. With the administration of heat the temperature of the skin rises, the rapidity of this rise depending on the thickness of the tissue it is less rapid when the superficial tissue is thinner allowing deeper penetration and faster dissipation of the heat by the blood (7). The study of the passage of chemicals through the skin, persorption, offers a great challenge to research workers in the field of dermatology. Much information has been gained in the past few years but much more is needed to treat the various skin disorders prevalent today (8). It would be out of place here to present all published data on skin struc- ture and physiology (9) and the literature on percutaneous absorption (10). These subjects have been reviewed before as listed in the bibli- ography. In general it has been found that a substance with water and lipoid solubility has a much better chance of passing through the skin than other types. The rate of penetration is related to the ether-water partition coeflqcient, and the barrier to be passed appears to be an aqueous phase separating two lipoidal layers. There are many exceptions to this so that each individual compound should be tested for persorption. Water itself ' has been studied for its persorption properties, but it has been found that the most important property of this substance is to keep the stratum corneum hydrated with resultant improvement in dry skin (11). The surface layer of epidermis usually contains only 10 per cent of moisture in the keratin as compared with 40 per cent in the deeper layers and 70 per cent below the stratum granulosum (12). The skin as a whole becomes a depot of water for the rest of the body in certain cases of electrolyte imbalance (13). It is possible that a trace of water may go through the membrane at the stratum lucidurn boundary but the eccrine sweat glands and hair follicles are probably the main pathways for any slight passage of moisture through the skin. It is interesting to observe that the diameter of the eccrine sweat gland opening is only about 30 microns or less. This small opening will undoubtedly prevent particles having a large diameter from entering this gland. The much narrower tube spirals down into the skin with only a double layer of cells along its lining this would facilitate persorption (14). The much larger hair follicle has a lining whose cells become more and more undifferentiated as it penetrates into the skin allowing easier passage of material. The sebaceous gland openings into the

PERSORPTION 119 hair follicle likewise are points of entry especially for fat soluble substances. In certain regions such as in the armpits the apocrine glands also open into the hair follicles and offer additional pathways (15). It is essential for good persorption to assure prolonged contact with the substance in an easily spread ointment base or lotion (16). Rubbing and pressure would certainly force more material into the skin openings. Washing the skin to remove sebum and other matter, including the "acid mantle" (17) that might interfere with the application, usually affords more rapid persorption. For deep fungal infection it is useful at times to remove the upper layers by abrasion (18) or with scotch tape (19) before administering the topical drug or it may be necessary to soften the keratin layer with alkaline solutions, or with organic solvents. Breaking the sulfide linkages in the keratin layer with reducing agents may also prove useful (8). Low concentration of salicylic acid softens the outer structures while higher strengths damage the tissue (20). Damaged epidermal tissue increases passage by permitting material to enter the blood and lymph vessels of the dermis directly (21). During persorption tests on intact skin, therefore, the investigator must exercise utmost care in preventing skin damage during cleaning or shaving the skin. Damage also changes the negative charge on the outside of the skin which usually repels anions. The methods of determining persorption merit consideration for by these means it is possible to compare drugs and drug vehicles, and obtain other pertinent data necessary to establish good therapeutic action. It is well to remember that experiments on laboratory animals do not always give the same results as are obtained with humans (22). Known amounts of ointments or solutions in enclosed containers or compresses (23) have been applied to the skin for various periods of time the difference between the original and final amounts represents the amount going into the skin. However, this quantity may remain in the epidermis without exhibiting persorption, or a part will go into the skin orifices with immediate persorp- tion, or produce a depot effect by liberating material gradually into the dermis. This difference may also be determined by extraction, but again this need not indicate persorption. Excretion of inuncted material or its derivatives in feces, urine, or breath or identification in tissues or organs proves persorption. The depth of percutaneous penetration has recently been investigated by means of radioactive (24) and fluorescent (25) ma- terials. By the former method autoradiograms give pictures of the tissues containing the test material at different depths, at various time intervals. Hydrocortisone appears to pass generally through the epidermis, and not preferentially through the hair follicles. However, radioactive chemicals with short wave emission may indicate a deeper penetration than actually obtained. The fluorescent method shows that oleic acid is very easily petsorbed it indicates that linoleates and oleates may be especially valu-