J. Soc. Cosmet. Chem. 26 29-46 (1975) ¸ 1975 Society of Cosmetic Chemists of Great Britain Factors which determine the skin irritation potential of soaps and detergents COLIN PROTTEY and TERRY FERGUSON* Presented on 28th August 1974 in London at the IFSCC VIIIth International Congress on 'CosmeticsmQuality and Safety' organized by the Society of Cosmetic Chemists of Great Britain. Synopsis---Skin-surfactant interactions have been examined using specific laboratory tesis with a series of pure SURFACTANTS. Effects of these compounds upon the STRATUM CORNEUM have been studied by means of KERATIN denaturation and the extraction of PROTEINS and AMINO ACIDS. It was found that strongly ANIONIC SURFACTANTS, such as sodium LAURYL SULPHATE, sodium LAURYL ETHER SULPHATE and sodium LAUROYL ISETHIONATE (Igepon A) had considerable activity, by virtue of their polar head groups, whereas sodium laurate and non-ionic ethoxylates had minimal effect upon the stratum corneum. The effect of lipophilic chain length of the surfactants was important in their overall activity, in particular, the lauryl moiety. PERCUTANEOUS ABSORPTION of RADIOACTIVELY-LABELLED surfactants by guinea-pigs in vivo has been studied sodium laurate and lauryl triethoxylate penetrated to a far greater extent than other compounds: lauryl hexaethoxylate, sodium lauroyl isethionate and sodium lauryl triethoxy sulphate, had lower penetrabilities and sodium lauryl sulphate and sodium LAURYL SULPHONATE were lower still. The effect of pure surfactants upon living cells was studied by means of measuring HISTAMINE release from rat peritoneal MAST CELLS in vitro. ALKYL SULPHATES, ALKYL ETHER SULPHATES and alkyl tri- and hexaethoxylates were potent mast cell lysins, whereas monoethoxylate and sodium laurate and sodium lauroyl isethionate were less effective. Chain-length studies showed that the capryl, lauryl- and myristyl moieties were the most potent lipophilic groups for releasing histamine. Some of these surfactants were applied directly to the skin of RATS and the overall skin response determined by visual examination. Sodium laurate caused erythema after 24 h applica- * Environmental Safety Division, Unilever Research Laboratory, Colworth House, Sharnbrook, Bedford. 29

30 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS tion, when other surfactants (sodium lauryl sulphate, ether sulphate, isethionate and non-ionic lauryl triethoxylate) had no effect. After 3 days of application, sodium lauryl sulphate had the greatest effect upon the skin in terms of dryness, scaling and cracking of the stratum corneum erythema and oedema. Correlation of these results are discussed. INTRODUCTION The skin irritation potential of soaps and detergents (hereafter termed surfactants) is an expression of the complex interactions occurring in the various regions of the skin following its exposure to solutions of these compounds. Often, in the skin of surfactant-treated laboratory animals (generally after exaggerated application) one may observe signs of primary cutaneous irritation, a response manifested by drying, scaling or even cracking of the stratum corneum, and oedema and erythema in the dermis. In this paper the complex response of skin has been defined in terms of the various types of skin-surfactant interactions which may occur and may contribute to the overall skin response. Specific laboratory test methods have been devised to study some of these interactions. In particular, the effects upon the stratum corneum have been examined by studying the way in which a series of highly pure model surfactants may denature keratin, a phenomenon which may contribute to the observed superficial skin rough- ness. Also, the extraction of soluble compounds from the stratum corneum by washing with surfactant solutions has been measured and related to the removal of natural moisturizer from the horny layer, an effect which may give rise to a lower water-binding capacity (1) and consequently a lower flexibility (2). The rates of percutaneous absorption (skin penetration) of highly pure radioactively-labelled surfactants have been measured using guinea-pigs in vivo. Skin penetration of surfactants is a prerequisite of their causing a response in the living cells of the epidermis and underlying dermis (3). The interaction of surfactants with the living cells of the epidermis and dermis has been studied indirectly by measuring the ability of highly pure sur- factants to release histamine from rat peritoneal mast cells in vitro. Histamine release from mast cells is an initial reaction in the development of erythema (4). In each of these experimental methods on aspects of skin-surfactant interactions we have obtained evidence that the observed experimental result is related to the chemical structure of the surfactant used.