TOXIC AND ALLERGIC COMPLICATIONS OF HAIR DYES 121 sensitization to compounds of quinone structure which are formed in the skin from agents which contain aromatic amines. Later Meltzer and Baer (40) reported a patient who presented many hypersensitivities to compounds not only having related structures, but apparently unrelated in their chemical makeup. It must be understood that very often the sensitizations are so specific to some particular side chain or chemical structure that the spectrum of cross-sensitivity is not wide. Baer and Leider (41) tested 20 subjects who were known to have allergic contact sensitivity or eczematous hypersensitivity to paraphenylenediamine by feeding them azo dyes which were certified for use in foods, drugs, and cosmetics. In seven of these subjects they were able to observe exacerbation of the skin lesions and in five additional cases an increase in itching was produced. The significance of such findings is extremely important in at- tempting to explain some of our persistent dermatoses. Here we have a definite known sensitization, but the dermatitis persists when known contacts were removed. Among such patients some of the persistence may be traced to azo dyes. However, unless the doctor were acquainted with the observations of these authors concerning certified food colors, he would never be able to explain and eliminate the recurrent derma- titis. Paratoluylenediamine may be used as a hair dye either in conjunction with or as a replacement for para. While it has been thought to be less toxic than para it is usually included with para and is considered nearly as irritating. The (United States) Food and Drug Administration has had definite evidence of injury from this dye and it is for this reason that it is banned along with para for use in the region of the eyes. Winter (42) has compiled the various aniline derivatives used in hair dyes. While many are known sensitizers there is very little published on their toxic or sensitizing properties as compared to para itself. The author would like to suggest that in view of what has been said concerning cross- sensitivity there is no doubt but that in many instances such relationships should exist between the compounds listed below and paraphenylene- diamine. Aniline derivatives used in hair dyes according to Winter: 1. Sulfo-paraphenylenediamine (also the sulfate and hydro- chloride). 2. Dimethyl paraphenylenediamine. 3. Metaphenylenediamine and meta-toluylenediamine. 4. Paratoluylenediamine. 5. Para-aminophenol (Rodinol) and ortho-aminophenol. 6. Sulfo-para-aminometacresol (Metol). 7. Sulfo-2,5-diaminophenol (Areidol). 8. Sulfo-orthoaminophenol.

122 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 9. Para-aminodiphenylamine. 10. Sulfo-para-aminodiphenylamine and its sulfate. 11. 1,4-Diaminodiphenylmethane. 12. Sulfo-diaminodiphenylamine. The United States Food and Drug Administration recommends the fol- lowing directions for making skin tests for hair dyes containing para: Directions for Making Skin Test 1. The hair dye in this package must never be used for dyeing the hair unless a preliminary skin test has been made. The skin test must be made each and every time before the hair is to be dyed, regardless of whether or not a skin test has been made at sometime previously. 2. The dye used for the preliminary test must be a portion of the article intended to be used for dyeing the hair. 3. The sample of dye to be used for the preliminary skin test should be mixed and prepared in exactly the same manner and according to the directions applicable to the actual use of the hair dye itself. 4. By means of a suitable applicator (clean camel's hair brush, cotton- tipped applicator, or other applicator) a streak of dye not less than a quarter of an inch wide and at least one-half inch long is made on the skin and scalp behind one ear. It is important that the streak of d•e extend into the hairy portions of the scalp as well as that portion of the skin that is hairless. 5. The streak of dye should be permitted to remain for at least 24 hours. The test should be read between 24 and 48 hours after applica- tion. Preferably the test area should not be covered with combs, hats, spectacles, or any other object. 6. Warning: If redness or burning, or itching, or small blisters, or any other type of eruption appear in the general area used for the skin test during the first 24 hours the individual is sensitive to the dye, and under no circumstances should it be used for dyeing the hair. Hair dyes should not be used when there is any disease or eruption present any- where on the skin or on the scalp. It has been my experience as well as that of others that too often the test is done just once by the average beauty parlor operator. Certainly, in questioning home users, there is often no attention paid to the test at all by most of the people I have interrogated. In 1952 the House of Representatives selected a committee to investigate the use of chemicals in foods and cosmetics with the thought in mind of a possible change in the Food, Drug and Cosmetics Act. A great many experts from all over the country were heard by this Com- mittee, which consisted of the following: James J. Delaney, New York, Chairman Thomas G. Abernethy, Mississippi E. H. Hedrick, West Vir- ginia Paul C. Jones, Missouri A. L. Miller, Nebraska Gordon L. Mc- Donough,, California Walt Horan, Washington Vincent A. Kleinfeld, Chief Counsel Alvin L. Gottlieb, Associate Counsel Franklin C. Bing, Ph.D., Consultant and Camille O'Reilly Agnew, Clerk.