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.

ANIMAL AND HUMAN TESTING IN SKIN CARE 201 an absolute clearance. Furthermore, the role of toxicologists or derma- tologists who investigate a material is not just to say how bad that material is but to do his level best to show how much good it may do. What is needed is not just the eliciting of toxic potential of each and every chemical ingredient, but rather some standard by which newly developed products can be compared with those of similar purpose that have been in use for some time. It is our opinion that during studies aimed at determining chemical toxicity, irritation and sensitization potentials, emphasis should be placed upon recording what the product does to the skin. We feel that to fully justify the expense involved in modernization of a product, the manufacturer is entitled to data which will establish that the new product is at least as effective as the old. For this reason and also because the irritation-sensitization tests become more meaningful, we constantly em- phasize the need for incorporating actual use conditions into basic toxicity studies. STATEMENT OF PROBLEMS In their most elemental form, the unfavorable reactions obtained from topically applied chemicals, are the classic primary irritation and second- ary sensitization phenomena. By definition (3), a primary cutaneous irritant is an agent which will cause dermatitis in the normal skin by direct action at the site of contact, if it is permitted to act in suflScient intensity or quantity for a suflScient length of time. A cutaneous sensitizer is an agent which does not necessarily cause demonstrable cutaneous changes on initial contact, but which may effect such specific changes in the skin that after a time interval of 5 to 7 days or longer, further contact at the same or at another part of the body will cause a dermatitis. Unfortunately, the division between irritants and sensitizers is not as sharp as one would like, and there is a great deal of chemical-immunological cross reaction. Recent work has shown that repeated exposure of an in- dividual to even a very weak irritant may so change the ability of the skin to resist damage that re-exposure to the same irritant at a later date may elicit a reaction similar in all respects to one due to an allergic sensitization (4). Such re-exposure primary irritation is often spoken of now as a "fatigue reaction" or the irritation reaction of repeated insult. The best way to look on these reactions is to consider that the irritant produces local damage to either the epithelium or to some physiological protective mech- anism of that epithelium, while the sensitizer produces a cellular antigenic change which permits that cell or even another cell in the body similarly changed to respond to an abnormal degree when next exposed to the stimulus. Practically, the accepted reaction may be divided into the following five groups: