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

GUINEA PIG ASSAY OF PHOTOSENSITIZING POTENTIAL 125 more than 1 in 10,000 is not acceptable from a safety or business point of view. An incidence of 1 in 100,000 or less is the desirable goal for such products. This report will be limited to a discussion of topical germicides for use in soaps and cosmetic products and to a description of a new lab- oratory procedure for assessing photosensitizing potential of topical agents on guinea pigs. TOPICAL CJERMICIDES Topical germicides to be fully acceptable for use in soaps and cosmetics must have the following properties: 2. 3. 4. 5. 6. The following attep. tion: Effectiveness against skin bacteria at low concentrations. Substantivity to skin. Compatibility with vehicles. Stability to light and heat. Activity in presence of soil. Safety--not a primary irritant, sensitizer, or photosensitizer. topical germicides have received the greatest 1. 2,2'-methylenehis (3,4,6-trichlorophenol) (Hexachlorophene) 2. 3,4',$-Tribromosalieylanilide (TBS) 3. 3,4,4'-trichlorocarbanilide (TCC) 4. 2,2'-thiohis (4,6-diehlorophenol) (Bithionol) 5. 3,3',4',$-tetrachlorosalicylanilide (TCSA) Tetrachlorosalicylanilide (TCSA), a germicide used in soaps, has been reported both in England and the United States to be a photo- sensitizer and has been promptly withdrawn from the market. This is an example of a biological agent that has passed conventional toxicolog- ical screening tests but was found to cause adverse skin reactions in some consumers after market introduction of soap containing TCSA. Bi- thionol has experienced similar difficulties but to a lesser degree and affecting a much smaller segment of the population. Jillson and Baughman (9, 10) reported on the photosensitizing action of bithionol on subjects characterized as persistent light reactors (PLR). Both TCSA- and bithionol-sensitized subjects were reported to be cross photosensi- tized, in some instances, to germicides like hexachlorophene and certain polybrominated salicylanilides.