120 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS causing secondary sensitization. The primary fi_llergen and the secondary allergen may be so closely related that the sensitized cell does not dif- ferentiate between them. The primary allergen can be converted in the body into an agent which is identical with or closely related to the secondary allergen. Furthermore, the secondary allergen can be converted in the body into an agent which is identical with or closely related to the pri- mary allergen. R. L. Mayer (32) pointed out in 1928 that the apparent occurrence and recurrence of dermatoses in workers who were once sensitized to para- phenylenediamine by further contact with apparently unrelated chemicals was really due to sensitization primarily to compounds of the quinone structure. Tzanck (33) and Sidi (34), as well as others, have demonstrated the ex- istence of cross-sensitization among paraphenylenediamine and local anes- thetics of a certain type. Apparently, here we have sensitization to a varying group in the para position. It is possible for a worker who has been sensitized to paraphenylenediamine to have a re-elicitation of his dermatitis upon receiving procaine as a local anesthetic. This also explains the development of dermatitis among patients who were sensitized to local anesthetics and showed spontaneous sensitivity to dyes of the paraphenyl- enediamine group. Such a case was recently reported by the author (35) where a physician who had been sensitized to the procaine part of the peni- cillin procaine also exhibited a four plus patch test to paraphenylene- diamine. This patient at the same time exhibited sensitivities among other local anesthetics as well as to picric acid solution. Cross-sensitization has been described between sulfonamide drugs and local anesthetics. Sulzberger, Kanof and Baer (36) observed cross-sensi- tization of para-aminobenzoic acid in a number of patients who had der- matiris due to sulfonamide drugs. Phillips (37) showed that in patients who had dermatoses from various sulfonamide drugs there was also a high incidence of hypersensitivity to procaine hydrochloride. In the patient reported by Peck and Feldman (35), there was sensitivity both to sul- fathiazole, benzocaine, para-aminobenzoic acid, pontocaine and butyn sulfate, but not to sulfanilamide. This is interesting in the light of Phillips' report that his patients showed a higher incidence of sensitivity to pro- caine hydrochloride than even to various members of some of the sulfon- amide group. Rogers (38) also reports a patient with sulfanilamide der- matiris who was sensitive to many of the local anesthetics. More recently, interest in the subject of cross-sensitization was further aroused by the work of Dobkevitch and Baer (39) who found cross-sensiti- zation between the azo dyes on nylon stockings and paraphenylenediamine. Cross-sensitization between azo dyes and paraphenylenediamine is ex- plained by the original studies of Mayer (32) as being primarily due to

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.