MECHANISM OF PERCUTANEOUS PENETRATION AND ABSORPTION 199 Of course, the principle of topical dermatotherapy as a whole rests on the creation of a locally high concentration of drugs in the skin without appreciable systemic effects. However, in dealing with lipid-soluble mate- rials which penetrate with ease through the epidermis, one should always be aware of the possibility of massive absorption and consequent undesir- able systemic effects. A particularly dangerous feature of topical applica- tions is that in most cases the absolute amount of the drug placed on the skin is not being measured. ABSORPTION FROM DERMATOLOGICAL AND COSMETIC PREPARATIONS An important feature of transepidermal absorption is that it apparently makes very little difference in what kind of vehicle, base or carrier the sub- stance to be absorbed is incorporated in when it is applied to the skin. It depends exclusively on the nature of the substance, whether it will become absorbed or not. Salicylic acid, for instance, will be easily absorbed from water, from alcohol, from greasy ointments, from oil-in-water emulsions and from water-in-oil emulsions. Sodium salicylate will not be absorbed from any of these bases. In this respect transepidermal absorption differs greatly frcm trans- follicular absorption. In the latter much depends on how the material is brought to the follicular pore. First, an increase in wetting will bring the material closer to the pore funnel. Using wetting agents the surface tension between liquid and air and between liquid and pore is diminished, droplet formation is prevented and a continuous surface layer can be main- tained at the liquid/solid boundary. Second, simply mechanically, i.e., by rubbing, the material can be pressed into the follicular canal. There- fore, ointments which are supple and can be easily spread and smoothly rubbed have a mechanical advantage over tough, tenacious, stiff or sticky ointments or aqueous and alcoholic solutions. Only in this mechanical sense is a "vehicle" a true carrier but never in the sense that it carries mate- rial into living cells. Data are available showing that vehicle and incor- porated drugs separate in the follicular canal. It is by no means clear what happens to the vehicle once the substance gets through transepidermally or transfollicularly. I mentioned that higher hydrocarbons are absorbed poorly if at all. Some data in the litera- ture indicate that follicular penetration is slower, the more hydrophobic the fat is, or at least that penetration of petrolatum is always poor as com- pared with that of triglycerides. The only instance I know of in which radioisotopes were used to clarify absorption of fatty substances used in ointment bases was the work of Barail and Pescatore who reported that if the U.S.P. cold cream is made up with spermaced which is labeled with C TM no permeation of this spermaceti can be demonstrated through human skin.

200 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS PROSPECTS FOR THE FUTURE In the field of percutaneous absorption through human skin, some frag- ments of knowledge have been put together in painstaking experiment during the last fifty years. But no matter how carefully the work was done it was always fraught with pitfalls, and the interpretation was difficu]t. I believe that with the advent of radioisotopes and radioautograph tech- niques a much more rapid progress can be expected. These new methods secure safer grounds than hitherto available. Possibly in the next few years all major problems in this field will be resolved. REYERENCES (1) Rothman, S., "Physiology and Biochemistry ooe the Skin," Chicago, University ooe Chicago Press (1954). (2) Szakall, A., Fette u. Seifen, 53, 399 (1951). (3) Szakall, A., •lrch. Dermatol. u. Syphilis, 194, 376 (1952), (4) Wolf, J., Z.f. mikroskop.-anat. Forsch., 47, 351 (1940). (5) Pinkus, H., 7. Investig. Dermatol., 16, 383 (1951). (6) Montagna, W., ?roc. Soc. Exp. Biol. Med., 86, 668 (1954). CORRELATION BETWEEN ANIMAL AND HUMAN TESTING OF MATERIALS USED IN SKIN CARE* By EUGENE F. TRAUB, M.D., HERBERT J. SPOOR, PH.D., M.D. New York Medical College, New York City IN RECENT years there has been an increasing demand for more effec- tive methods of pretesting cosmetic and pharmaceutical products. This demand has been brought about not only because of the increased use of newer untried ingredients but also because there have been some instances of definite damage occasioned through use of presumably adequately tested products (1). It is becoming very clear that the methods which have been used in the past on either animal or human skins are in themselves not suf- ficient to give an absolutely clean bill of health to a cosmetic preparation. Our discussion will be an attempt to re-evaluate the testing methods that have been used in the past and, in the light of more current developments, we will propose certain modifications in procedure which may make pre- testing methods more ideal. There is one basic chemical point which should be made at this time, and that is that all materials applied to the skin in either cosmetics or pharmaceuticals are foreign to the skin and as such they are a definite hazard whenever they are applied (2). Obviously then, everything used on the skin must be pretested for this toxicity on either animal or man. It is apparent that nothing can be given * Presented at the September 23, 1954, Seminar, New York City.