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:

202 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS (a) Primary irritation reactions, which are direct damage by the chem- ical to the epithelium. This is essentially a contact injury and it is well illustrated by the reaction which follows exposure to mustard oil or any similar vesicant used as a counterirritant. (b) Fatigue reactions which are those primary irritant reactions which require more than one exposure to be elicited. The irritation seen follow- ing prolonged use of a soap is an example of the fatigue reaction. It should not be confused with the milder primary irritation common to most soaps which we shall mention later as "soap reaction." (c) Delayed irritant reactions which although not present immediately after contact with the chemical, can become apparent several days to several weeks later and present skin damage at the site of application. This type of reaction is somewhat characteristic of the newer plastic materials used in cosmetics. It is also frequently seen when one tests the various impreg- nation materials used for weatherproofing cloth. (d) The true sensitization reactions, which are those due to allergic change of some receptor in the host tissue. A dramatic example of a re- action of this type is that very frequently given by perfumes. (e) Systemic toxic reactions, which may occur after absorption of a toxic chemical from the skin surface. In this latter category it is apparent that the physical state of the product and its manner of usage may de- cidedly influence its potential systemic toxicity. One of the most notori- ous examples of this type in the dermatological field was the product "Koremlu." This thalium acetate preparation was marketed as a depil- atory.* The material actually had no local action, but when absorbed did cause loss of hair, particularly that of the scalp. The action was that of a systemic toxicant the fatalities which were caused by the drug should have been anticipated. The product should never have been sold. (f) Another type of reaction we would like to call attention to is that referred to commonly as "hardening." This reaction is probably the con- verse of the fatigue reaction and represents that condition wherein the skin once irritated by a chemical becomes toughened to that chemical so that subsequent exposures cause little appreciable damage. We have in mind a dentifrice which we tested and which will be mentioned in this connectio• in more detail later. RESTATEMENT OF SUBJECT OF DtSCUSS•ON Correlation Between dnimal and Human Testing of Materials in Skin Care In general there is a direct interdependence between animal and human testing so that rather than a correlation of the two, one should attempt to * Prior to 1930. Ed.