Halogenated salicylanilide

The answer is d. (Hardman, p 1019J Niclosamide is a halogenated salicylanilide derivative. It exerts its effect against cestodes by inhibition of mitochondrial oxidative phosphorylation in the parasites. The mechanism of action is also related to its inhibition of glucose and oxyrgen uptake in the parasite. 

Halogenated salicylanilide photoproducts are believed to be formed in this fashion. 

Chignell, C.F. and Sik, R.H (1989) Spectroscopic studies of cutaneous photosensitizing agents. XIV. The spin trapping of free radicals formed during the photolysis of halogenated salicylanilide antibacterial agents, Photochem. Photobiol., 50, 287-295. 

Niclosamide. This drug (6) is a halogenated salicylanilide derivative, C13H8Q2N204. 

Other cosmetic ingredients, cited in the literature for phototoxic reactions, are 6-methyl coumarin (formerly used as a fragrance component of sun protection and facial products) and halogenated salicylanilides (previously used in antibacterial products such as deodorant soap bars) [188]. 

The halogenated salicylanilides (tetrachlorosalicylanilide, brominated salicylanilides) and related compounds caused an epidemic of adverse reactions to sunlight between 1960 and 1970, when they were incorporated as antibacterials in soaps and cosmetics (Wilkinson 1961 Calnan et al. 1961 Epstein et al. 1968). After 1968 a striking reduction in numbers of patients with positive photopatch tests to these compounds has been noted (Smith and Epstein 1977), and explained partly by removal from the market of the more potent photosensitizing chemicals, partly by increased awareness by physicians. 

Osmundsen (1970 b) showed a varying cross-photoreaction pattern between halogenated salicylanilides and related compounds (salicylanilide, hexachloro-phene, trichlorocarbanilide, fenticlor, Jadit, 2,4-dichlorbenzylalcohol, and zinc omadine). 

Bithionol (2,2-thio-bis-[4,6-dichlorophenol]) is a bacteriostatic agent related to hexachlorophene. It produces both contact allergy and photocontact allergy and cross-reacts with hexachlorophene and the halogenated salicylanilides. The use of bithionol is now restricted in the United States but reactions still occur occasionally from old stock preparations (O Quinn et al. 1967). 

Freeman RG, Knox JM (1968) The action spectrum of photocontact dermatitis Caused by halogenated salicylanilides and related compounds. Arch Dermatol 97 130-136 Fregert S (1968) Cross sensitization among nitrofurylaminothiadazoles. Acta Derm Vene-reol (Stockh) 48 106-109... 

Smith SZ, Epstein JH (1977) Photocontact dermatitis to halogenated salicylanilides and related compounds. Arch Dermatol 113 1372-1374 Sneddon IB, Glew RC (1973) Contact dermatitis due to propanidid in an anaesthetist. Practitioner 211 321-323... 

Wilkinson DS (1962) Patch test reactions to certain halogenated salicylanilides. Br J Dermatol 74 302-306... 

Dichlorophene (Anthiphen, Dicestal, Didroxane, Di-phenthane-70, G-4, Hyosan, Parabis, Plath-lyse, Preventol G-D, Teniathane, Teniatol, Wespuril, CAS no. 97-23-4). This is a biocide in many soaps, shampoos, hair tonics, liquid make-up products, etc. As a preservative in many dentifrices, it has caused dermatitis of the mouth, mostly allergic, with cheilitis and stomatitis (Andersen and Ham-ann 1984). The patch-test concentration is 1% pet. Irritant patch tests are common. Photoallergic reactions are reported (Menz et al. 1982). Crossreactions with bithionol, hexachlorophene and halogenated salicylanilides are possible. 

Tribromsalan (TBS, halogenated salicylanilide, Temasept IV, Tuasol Hostynek 1989, CAS no. 87-10-5). This is an antiseptic that is now prohibited in the EC. Photoallergic and phototoxic reactions were reported (Miyauchi and Horio 1992). Cross reaction occurs with other halogenated salicylanilides. The patch-test concentration is 1% pet (Osmundsen 1970). 

Cross (photo) bithionol and other halogenated salicylanilides, triclocarban, hexachlorophene, fentichlor. PA, PT A... 

As in the case of membrane-active phenol derivatives (see Section 5), the halo-genation of salicylanilides or carbanilides increases the antimicrobial efficacy. The best results are obtained by means of di- to penta-chlorination or bromi-nation, the halogen atoms being more or less evenly distributed on the two phenyl rings. On the other hand halogenated salicylanilides have photosensitizing properties, which has reduced their practical importance. 

Fasciolicidal action was also reported for another series of salicylanilides in which an electronegative substituent was introduced in the 3-position. The choice of substituents in the aniline ring was restricted to halogens, methyl groups and tri-halogenated methyls (which improve lipid solubility). The most effective compounds were 3-nitro-2,6-dihydroxybenzoic acid anilides. 

Cosmetic manufacturers may use essentially any raw material as a cosmetic ingredient insofar as it is not considered as only a drug active ingredient, and market the product without approval. The law regulates only colour additives specifically approved for cosmetics and a few prohibited and restricted ingredients (e.g. bithionol, mercury compounds, vinyl chloride, halogenated salicylanilides). Cosmetics should not be contaminated with nitrosamines, 1,4-dioxane and pesticide residues, whose potential presence is regularly checked by the FDA (see Section 2.1). 

Finally, in Japanese legislation there is also a positive list of preservatives, similarly to the EU, but where the permissible substances and authorized contents are quite different. Moreover, there is a list showing different substances whose use is banned in cosmetics, including hexachlorophene, bithionol and halogenated salicylanilides among others, like in the aforementioned two legislations. 

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