PHOTOSENSITIVITY 89 MECHANISM OI* PHOTOSENSITIZERS Photosensitizers act by virtue of photodynamic action--a term used to describe the interaction of light and a photosensitizer in the presence of oxygen, causil•g a destructive photochemical reaction. Four criteria must be met. First, the compound must be present in the living epidermal cell and must have gotten there by virtue of ab- sorption either parenterally or by topical application. Secondly, the compound must be of specific nature. In a study of contact dermatitis the authors showed that, in a subject previously sensitized to a phe•.othiazine derivative co1•taining a chlorine atom in the ring, positive skin reactio•..s were elicited by patch testing only with compounds having a chlorine in the 2-position. Other atoms or radicals gave negative reactions. The structure of the side chain did not seem to be a critical factor in causing contact (allergic) sensitization. In this case exposure to strong mid-day sunlight did not bring out any latent reactions and did not seem to affect the severity of the skin reaction (17). The experimental data suggest a possible structure-activity rela- tionship, which may be a factor in the development of allergic skin reactions following contact with certain phenothiazine derivatives. Furthermore, sensitization of this type may be related to other side reactions the manifestations of which strongly suggest an allergic basis for this reaction. Other investigators found no reactions with other phenothiazine derivatives lacking the chlorine atom (Diparcol and Parsidol) in patients who had positive patch tests to chlorpromazine It has recently been shown that subjects could be cross-photosensi- tized to all of the halogenated salicylanilides tested except tribromo- salicylanilide. It appears, therefore, that TBS is not a cross-photo- sensitizer, although with the chlorine analog cross-photosensitization does occur (19). Demethylchlortetracycline induces photosensitivity of the phototoxic type in approximately 20% of ambulatory patients receiving ordinary therapeutic doses (6). It is of considerable interest why demethylchlor- tetracycline possesses such a marked capacity to photosensitize while the other three congeners are much less capable of inducing such a reaction (20). The frequent association of light sensitivity reactions with drugs containing a free chlorine radical has been pointed out (21) however, chlortetracycline also possesses such a radical, and photo- sensitization rea. ctions to it have been distinctly unc. 9,,m,,•,,.on. Thus

9O JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS attention is focused on the substitution of a hydrogen for a methyl group at the R• position. This alters one of the central rings at the meso position and suggests a possible analogy with compounds which have an anthracene-like structure and whose photosensitizing capacity can be increased by change of one or more of the meso or para atoms of the central ring (22). The precise molecular specificity is shown by the effect that structural alteration has on the erythemal activity of furocoumarins and makes the difference between an inert and active compound (5). Thirdly, light of an effective (proper) wavelength, and in adequate quantity, must reach the skin. Hence source, exposure time, atmos- pheric conditions, thickness of stratum corneum, and melanin content all may cause differences in quantity of light reaching the epidermal cell. The specific band of light which elicits the photosensitivity reaction is the action spectrum. Each photosensitizer has its own specific absorption spectrum, which usually matches the action spectrum but not always. The only radiant energy capable of producing photodynamic action is the ultraviolet or visible. Some examples are: Fluorescent dyes (3900- 7900 A) sulfonamides, chlorpromazine, demethylchlortetracycline (2900-3100 A) 8 methoxypsoralen (2700-3200 A). Finally, oxygen is necessary (2, ,5). Diagnosis is complicated because one has to decide whether a partic- ular reaction is photoxic or photoallergic. As Baer and Harber point out, the morphological characteristics of the eruption and a knowledge of the incidence of the adverse reaction and the concentration of the drug necessary to evoke it are often crucially important in arriving at a decision. Also, tests used in making a diagnosis of drug-induced photo- sensitivity are usually based on reproducing the lesions under controlled conditions with known types and amounts of artificial light (23). Treatment for acute phases of photodermatitis is similar to that used in treating other dermatoses (24) usually rapid improvement occurs if the photosensitizing agent and sunlight in the responsible wavelength spectrum are avoided. (Received November 18, 1965) REFERENCES (1) Epstein, S., J. Invest. Dermatol., 2, 43 (1939). (2) Blum, H. F., Photodynamic Action and Diseases Caused by Light, Reinhold, New York, 1941. (3) Lamb, J. H., et al., Arch. Dermatol. and Syptz., 62, 1 (1950).