236 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Semi-stable ones are required, but even here coarse ones will leave the oil on the surfaces of the skin while extremely fine ones will penetrate too deeply and make the leather flaccid--a property not generally desired. Of course, mechanical squeezing by drumming is resorted to in order to speed the process. In a way, this simulates flexing, and everyone knows that to wet a chamois leather with water is a long job unless the leather is "worked." This particular feature is one of the essential processes of topical application to the living skin. The mere rubbing of oil on a wet surface helps considerably to bring about wetting of the substrate, probably because such ingredients as may be polar can reach the water interface and lead to spreading. There is significant evidence that proteins have oleophilic properties, and an orientated film of oil will be able to cling to a fibre surface if it can be forced into contact and may quite well de-wet the surface of collagen fibres, and even though a detergent be present, some of the oil may be bound. This certainly applies to wool, which cannot be absolutely freed of grease by the ordinary detergents of commerce.* The manufacturer of leather can employ many artifices which would be impossible with the living skin. He can bring the pelt to any pH value he chooses. He can open up the structure by treating the skin with a suspension of calcium hydroxide (pH 12.4) which also disperses and gets rid of most of the interfibrillary proteins. He can treat the limed pelt with tryptic enzymes to clean the collagenous fibrous tissue further. He can treat the skin with acids to bring the proteins to pH values of 4 to 5, where the packing together of the fibres is about minimum. He can subject the skin to some- what severe pressure and agitation to assist penetration. Nothing Like this is available to the cosmetician. On the other hand, it must not be overlooked that the living skin is continuously moving. Although this movement is small, it nevertheless has a profound effect. The fact that the tissues of the skin, except the outer layers of the epidermis, are bathed in a stream of fluid means that substances which do enter the cutis vera will be carried away, utilised or destroyed by the Living organism to its own ends. How far substances can penetrate into the living structure is prescribed by the effectiveness of the epidermis as a barrier. It is beyond argument that a damaged epidermis is a serious matter. The literature covering penetration of living tissues is vast. Even if one excludes such aspects as, for example, the permeability of the cell walls of bacteria or blood corpuscles, that relating to skin is still immense. It is almost impossible to find any hypothesis which can explain the mechanism by which all forms of penetration occur. There are a few facts, however, which are reasonably proven. Firstly, it is true that water-soluble substances, provided that they are

PENETRATION OF SKIN--DEAD AND ALIVE 237 uncharged, can penetrate the skin. This property is enhanced if the sub- stance is also soluble in oil. It would even seem that preferentially a sub- stance should be both hydro- and oleophilic. Secondly, oleophilic substances can also be absorbed through the skin, their efficiency depending on the presence of polar groupings and their viscosity at about blood temperature, together with' the manner in which they are applied. Consider the cases of sodium and potassium chlorides. The mobility of the sodium ion is significantly less than that of the chloride ion, so that this substance in solution at a semi-permeable membrane will diffuse unevenly and set up a membrane potential which will retard and eventually prevent further passage of the sodium chloride. The potassium salt will continue to diffuse insomuch as the mobilities of the two ions are sensibly equal. This property is, of course, fully utilised when saturated potassium chloride solution is used as a bridge in potentiometric determinations. Equality of mobility of its ions makes water the centrepin of life. Substances which are completely ionised are not those which can penetrate unless some means is employed for preventing the ionisation. Prevention of ionisation can be accomplished in many instances by the use of a substance like ethylene diamine tetra-acetic acid. Unfortunately, this material, although assisting magnesium, calcium and other metals to pass through a membrane, if it reaches the blood stream it can pick up other metals and assist their passage through the membranes of the excretory organs.' To this extent, E.D.T.A. is a noxious substance and is not permitted for use in foodstuffs. It should not be employed as a means of increasing the permeability of skin. One of the substances which is outstanding in its power to penetrate tissues is ammonia, and yet ammonium salts have little power to do so. This is because the ammonium ion NH4 + will set up a membrane potential. It has to be remembered that in a solution of ammonia in water there are present NH3 and NH•OH in the equilibrium, NH3 q- H•O • NH40H • NH+• q- OH- but there is always some un-ionised ammonia. Being a small molecule it can pass through the membranes and its loss from the solution will be automatically made up by the liberation of more NH3 from the ammonium hydroxide in order to maintain the equilibrium. Iodine can also function in a somewhat similar fashion provided that the base in which it is dissolved is suitable. One of the ways in which substances can be made to penetrate is by means of esterification. One of the earliest substances to be investigated was salicylic acid. By itself, its penetrating powers are low, but when esterified