USE OF ANTI-IRRITANTS IN COSMETIC FORMULATING 321 The specific protective mechanism depends on the nature of both the irritant and the anti-irritant used. Since very little reliable data on the subject are currently available, the following is necessarily speculative. At this writing, there seem to be three routes of action by which anti-irritants can confer protection. None of these three routes fits the "intuitive" picture of an anti-ir- ritant as "a soothing ingredient which heals the skin and thus repairs or reduces the damage concurrently being caused by the irritant." The three mechanisms postulated are: (i) By "Complexing" the Irritant This is the never-never land of chemistry. Molecular adducts (complexes) are known to form between many materials. The bonding is often quite loose complexes sometimes seem to exist and then not. Their properties are equally bewildering. The PVP (polyvinyl pyr- rolidone) iodine complex is a classic case: Adding PVP to elemental iodine results in a product which does not produce normal iodine stains, has no detectable vapor pressure, is completely nonirritating to mucous membrane and skin, and whose acute toxicity is only one-tenth that of elemental iodine yet its germicidal activity is higher than that of iodine alone. For all practical purposes, therefore, it is detoxified iodine (1). Similar complexes of iodine can be formed with nonionic (5) and cationic (6) surfactants. It has also been shown that urushiol, the irritant material in the poison ivy leaf, can be detoxified by com- plexing with zirconia (7), silver salts and certain ion exchange resins (S). (ii) By Preventing Complete Contact with the Skin Many thickening agents seem to reduce irritation, especially eye irritation caused by products such as shampoos. It has even been reported (9) that methyl cellulose allows the eye to tolerate dilute solu- tions of sodium hydroxide, The reason postulated was that the thick- ening agent did not allow the irritant to spread easily thus the solution was not in actual contact with all of the cornea. There is perhaps a more subtle reason why gums and thickeners sometimes act as anti-irritants: If a rigid chunk of irritant is put on the skin, only that portion in direct contact can cause irritation and the concentration of irritant at that point soon drops, due to reaction with the skin. The softer the irritant mass, however, the better is the initial contact with the skin and the greater is the likelihood that the

322 JOURNAL OF THE SOCIETV OF COSMETIC CHEMISTS irritant can diffuse throughout the mass. As the local concentration is depleted by reaction with the skin, more irritant continually diffuses to the point of skin contact. Any material which retards diffusion thus reduces skin irritation simply by reducing the total amount of irritant making contact with the skin. Irritant motility can be reduced by thickening or even by complexing in such a way as to reduce solu- bility in the vehicle. Another way of reducing contact between the skin and irritants is the use of emulsions with the irritant present only in the discontinuous phase. For example, use of W//O emulsions as vehicles for water- soluble irritants generally results in the skin being "wet out" first by the oil phase. This oily layer on the skin can then act as a physical barrier against contact with the hydrophilic irritant. (iii) By Blocking he Reaction Si es on the Skin There are various ways of doing this. One is the use of a phe- nomenon which is primarily physical, i.e., adsorption of oils onto keratin (see ii). Many highly nonpolar fatty materials (such as mineral oil) adsorb very strongly onto keratin (10, 11). Small amounts of these oils in shampoos adsorb on the hair and leave a sheen, even though the active ingredients of the shampoo are excellent emulsifiers for just such oils. In antiperspirant emulsions, inclusion of mineral oils and waxes may reduce irritation by oil-insoluble astringent alu- minum salts via this type of selective adsorption. Keratin is also highly reactive chemically. It is amphoterie, react- ing with both acids and bases. The eysteine portion of the softer keratins reacts readily with heavy metals, forming mercaptides. Keratin is also fairly susceptible to oxidation and reduction, and to materials such as phenols or urea which affect its hydrogen bonding. All of these are routes by which irritants may attack the skin chemically, and by which anti-irritants may also react with it in such a way as to block further reaction with irritants. When anti-irritants exhibit very specific protective activity, it is probably due to chemical reaction with the irritant. When the protection is of a broader nature, the probable mechanism is via some sort of reaction with the body keratin. PRACTICAL APPLICATION The foregoing theoretical discussion will now be illustrated with the aid of some practical examples.