NATURAL COLOR PIGMENTS OF THE HAIR 13l should be producing melanin. This appears to represent repression of hair growth with greater repression of pigment formation. Monobenzylether of hydroquinone and guanofuracin are two compounds which can produce depigmentation. Guanofuracin produced depigmentation of the eye- lashes when used in the eyes (17). Histologic studies of skin following application of these compounds suggest that they interfere with basic granule formation. The Vogt-Koyanagi syndrome and some reactions of monobenzylether of hydroquinone and guanofuracin involve an allergic mechanism. The antigen is presumed to be melanin. These reactions may lead to widespread depigmentation of skin and hair. Phenylthiourea and alphanaphthylthiourea are excellent inhibitors of tyrosinase. They probably produce depigmentation by enzyme inhibition. Molybdenum interferes with copper. Depigmentation occurs because tyrosinase is a copper protein. The mechanism of vitiligo is unknown. From the facts that are known it appears to differ from the above mechanisms. Other examples could be cited. It seems obvious that normal variations, dis- eases and chemicals resulting in depigmentation do not function by the same mechanism. Increase in hair color appears to involve a single mechanism, increase of tyrosinase activity. This is frequently coupled with hair growth so that the metabolism of the entire hair follicle may also respond. Chronic irritation of the skin, rubbing or biting, leads to the increased formation and darkening of hair. The use of psoralens, photosensitizers, and sunlight will result in increased length and darkening of the hair. It is possible to repigment some gray hair in this way. Inflammation of the scalp, such as a boil, in a person with gray hair may lead to the production of a small patch of dark hair (18). Simple inflammation of the scalp from any cause will tend to increase growth and darkness of hair. This response provides a limiting factor of sorts to strong bleaching agents. When a bleach irritates the skin the dark roots appear more rapidly. How likely is a chemical to interfere with normal hair color? Mono- benzylether of hydroquinone is used as a depigmenting agent. The pso- talens are photosensitizers and their darkening effect was predicted. Chloro- quine diphosphate, hydroxychloroquine diphosphate, guanofuracin, me- phenesin carbamate and diodoquin are therapeutic compounds whose depigmenting effect on the hair was unexpected. There are other poisonous materials which cause alepigmentation of the hair. None of these prepara- tions has been completely investigated in human hair. A practicing physician cannot be expected to continue a therapeutic agent producing a marked cosmetic defect. I am aware, however, of dark blond to brown haired patients in whom chloroquine diphosphate has produced platinum blond bleaching of the scalp hair, eyebrows, eyelashes and pubic hair. Chloroquine diphosphate in adequate dosage for an adequate time would

132 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS very likely convert all red, blond and brown haired individuals to complete platinum blonds. It might ultimately convert them all to brunettes. Since the melanocytes of the skin do not contain a pheomelanin system, there would be no effect on skin color. Bleaching of dark hair would involve blocking the tyrosinase system. The melanocytes of the skin contain the same enzyme and there would be an excellent chance of altering skin color. In two patients with guanofuracin depigmentation the eye- lashes became white but not the eyelids (17). In only twenty-seven per cent of the cases did depigmentation of the eyelids and eyelashes appear at the same time (19). There is a differential in the sensitivity, not well defined, between the hair melanocyte and the skin melanocyte. These reactions are so far beyond our basic knowledge that the only way to find out what will happen is to try it. In light of past experience future chem- icals will probably produce more surprises. SUMMA RY The hair pigment is more complex than has been assumed. Dark hair contains melanin it is a good assumption that blond, red and light brown hair contains pheomelanin and there is a slight possibility that red hair also contains trichosiderin. The control of hair pigment is extremely complex and mostly a mystery. The theoretically perfect bleach, i.e. cessa- tion of pigment formation in all hair is scientifically possible. Practicality of this reaction awaits evaluation. REFEKENCES (1) Zimmerman, A. A., and Becker, S. W., Jr., "Illinois Monographs in Medical Sciences," Vol. 6, No. 3, Urbana, Univ. of Illinois Press (1959). (2) Chase, H. B., "Biology of Hair Growth," Montagna, W., and Ellis, R. A., editors, New York, Academic Press, Inc. (1958), p. 229. (3) Barnicot, N. A., and Bitbeck, M. S. C.,Ibid., p. 329. (4) "Pigment Cell Biology," Gordon, editor, New York, Academic Press, Inc., (1959), p. 549. (5) Lerner, A. B., and Fitzpatrick, T. B., Physiol. Revs., 30, 91 (1950). (6) Fitzpatrick, T. B., and Kukita, A., "Pigment Cell Biology," Gordon, editor, New York, Academic Press, Inc. (1959), p. 489. (7) Commoner, B., Townsend, J., and Pake, G. E., Nature, 174, 689 (1954). (8) White, L. P., Ibid., 182, 1427 (1958). (9) Alving, A. S., Eichelberger, L., Craige, B., Jones, R., Whorton, C. M., and Pullman, T. N., 5 t. Clin. Invest., 27, 60 (1948). (10) Saunders, T. S., Fitzpatrick, T. B., Seiji, M., Brunet, P., and Rosenbaum, E. E., 5 t. In- vest. Dermatol., 33, 87 (1959). (11) Butenandt, A., Biekert, E., and Linzen, B., Z. physiol. Chem., 305, 284 (1956). (12) Butenandt, A., Keck, J., and Neubert, G., Ann., 602, 61 (1957). (13) Butenandt, A., Biekert, E., and Neubert, G., Ann. 602, 72 (1957). (14) Rothman. S., and Flesch, P., Proc. Soc. Exptl. Biol. Med., 53, 134 (1943). (15) Fitzpatrick, T. B., Brunet, P., and Kukita, A., "Biology of Hair Growth," Montagna, W., and Ellis, R. A., editors, New York, Academic Press, Inc. (1958), p. 255. (16) Van Scott, E.,Ibid., p. 441. (17) Yamada, M., 5tapan. 5 t. Dermatol., 66, 435 (1956). (18) Pinkus, H., A.M.A. Arch. Dermatol., 82, 263 (1960). (19) Kobori, T., and Yamada, M., personal communication.