J. Soc. Uosmetic Chemists, 17, 123-130 (1966) A Guinea Pig Assay of the Photosensitizing Potential of Topical Germicides LEONARD J. VINSON, Ph.D., and VINCENT F. BORSELLI, B.S.* Presented September 8, 1965, New York Chapter Synopsis--In recent years there has been increasing use of germicides in soaps, detergents, and cosmetic products to provide significant benefits in the control of odor and minor second- ary infections. Even though these agents are carefully screened for safety and effectiveness, an occasional one which reaches the mass market is found to be a marginal sensitizer that escaped detection in animal tests and limited human panel studies. A guinea pig assay procedure is described which measures the photosensitizing potential of topical germicides. Data are presented relating the photosensitizing and cross photo- sensitizing activities of commercial germicides, viz., bisphenolics, halogenated salicylanilides, and halogenated carbanilides. Tetrachlorosalicylanilide and, to a lesser degree, bithionol are observed to be photosensitizers. The significance of these findings and results on other germicides in predicting the acceptability of a topical agent in soaps and cosmetics is dis- cussed. INTRODUCTION Photodermatitis is a phenomenon that has been known for many years. As far back as 1897, Stowers (1) described a case of skin eruption due to exposure to sunlight after contact with wild parsnips. Derma- titis in some individuals following use of eau de Cologne and exposure to sunlight was found to be due to certain essential oils oil of bergamot being chiefly responsible. Klaber (2) coined the name phytophoto- dermatitis for the skin condition resulting from contact with certain * Lever Brothers Co., Research Center, Edgewater, N.J. 123

124 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS plants or their extracts followed by sun exposure. Some of the plants implicated in addition to wild parsnips are carrots, pink rot celery, persian lime, fig, buttercup, lady slippers, and many others. More recently, certain drugs and cosmetic ingredients have been reported to have photosensitizing effects on som_e individuals. Included are the sulfonamides, coal tar and derivatives, psoralens, and the phenothiazine drugs. Among the cosmetic ingredients implicated are lipstick dyes and sun-screening agents. Price gave an excellent review of photocon- tact dermatitis (3). Certain germicides have been reported to be photo- sensitizers, and one in particular, tetrachlorosalicylanilide, has received considerable notoriety (4-7). Unlike therapeutic agents, where a certain amount of risk may be justified to achieve cure, agents such as germicides for use in cosmetic and soap products must be carefully and thoroughly screened so as to avoid undesirable skin reactions. However, to find useful agents that provide effectiveness with safety for 100 per cent of the population is quite impossible when one considers the wide range in the biologic response of man. Many factors are involved in trying to predict how skin will react to a topical agent. Some of the principal ones are: 1. Toxicity of the material. 2. Its allergic potency. 3. Concentration of the active ingredient. 4. Frequency and duration of use. 5. Nature of vehicle employed. 6. Environmental factors--temperature, relative humidity, and sun- light. 7. Sensitivity of the individual--genetic factor. The problem of ascertaining the irritation potential of most agents, both primary irritants and sensitizers, is not a formidable one. Stand- ard toxicological procedures which have proved useful are described in the FDA sponsored book on methods for safety evaluation of chemicals (8). Agents capable of inducing skin reactions in 1 in 100 or even 1 in 1000 subjects are readily detected in such tests, but it becomes increas- ingly difficult to predict the irritation or sensitization potential of a preparation causing skin reaction in 1 in 10,000 or even 1 in 100,000. This is particularly true for topical agents having weak photosensitizing properties. It is this particular type of agent that concerns those who are responsible for passing on the safety of soaps and cosmetics that are used by millions of people. A photosensitizing response occurring in