320 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS A major purpose of this paper, therefore, is to present irritation test data showing specific anti-irritant activity, or lack thereof, for a number of agents which have been claimed to possess this property. The use of such adjuncts is becoming ever more important in formu- lating cosmetics and toiletries. Many countries are now adopting laws which will circumscribe the ability to formulate freely. Since these laws result primarily from increased governmental concern over the safety of cosmetic products, it is evident that we need to know whether certain agents can serve as anti-irritants, so that they can be used with assurance when the need arises. DEFINITIONS AND MECHANISM OF ACTION For purposes of this discussion, an anti-irritant is not merely a material which is soothing to the skin or which helps heal already existing skin irritation. Neither is it simply a lubricant film or coating of powder or cream which reduces frictional (chafing) skin irritations. Broadly defined, an anti-irritant is an agent which, when used in conjunction with skin or eye irritants, reduces their irritation potential suj•ciently so that they can be tolerated when applied to the body. Does this include all anti-inflammatory agents? No. Even though such activity is evidently beneficial and often may be desirable, anti- inflammatory activity per se cannot reduce opacification of the cornea nor prevent degradation of other tissue by corrosive agents. The fact that certain agents act as topical anesthetics is sometimes a "fringe benefit" if they are also anti-irritants. This quality alone however, does not make them anti-irritants. In one classic case (4), the inadvertent use of a mildly anesthetic wetting agent (in a per- manent wave neutralizer) resulted in increased eye irritation for the simple reason that, feeling no pain, users who accidentally introduced the product into their eyes made no effort to rinse it out. Occlusion of the skin by lipophilic materials can prevent irritation caused by aqueous irritants if they are thereby prevented from contact- ing it. Combining the two is not always beneficial, however. A lipophilic film-former can increase irritation if it forms an oc½lusive layer over the irritant and holds it in better contact with the skin. These exceptions merely point up the fact that anti-irritant activity is usually quite specific. The agent which works well in conjunction with one irritant may work poorly or not at all with another. Formation of physical or chemical barriers to prevent the irritant from contact- ing the skin is only one way by which anti-irritants can confer protection.

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