Photocontact dermatitis to halogenated salicylanilides and related compounds. Our experience between 1967 and 1975

Smith, S. Z.

doi:10.1001/archderm.113.10.1372

Cited by 9 publications

(2 citation statements)

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“…Interestingly, these agents belong to the family of halogenated salicylanilides and related compounds, which were widely used between 1960 and 1970 as antimicrobial agents by various manufacturers in soaps and cosmetics (10–12). It is remarkable to note that these molecules have been prohibited in Europe since the 1970s because of their responsibility for an epidemic‐like outbreak of contact photodermatitis and the development of chronic actinic dermatitis or persistent photosensitive states (13–18). In addition, the personal histories of our patients did not support the relevance of these positive photopatch tests, except for chlorhexidine.…”

Section: Discussionmentioning

confidence: 99%

Spectrum of cross‐photosensitization in 18 consecutive patients with contact photoallergy to ketoprofen: associated photoallergies to non‐benzophenone‐containing molecules

et al. 2003

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Contact photoallergy to ketoprofen gels has been widely reported, and cross-sensitivity reactions with other compounds, such as tiaprofenic acid, fenofibrate and benzophenones, are well known. However, positive photopatch tests to other different non-benzophenone-related compounds have recently been observed. We report the results of photopatch testing in patients with contact photoallergy to ketoprofen and discuss the spectrum of cross-sensitization to ketoprofen. 18 consecutive patients with a history of photocontact dermatitis from ketoprofen were investigated. Patch and photopatch tests were performed. As expected, we observed positive photopatch tests to Ketum* gel and ketoprofen 2.5% in petrolatum in all patients (100%). However, it was remarkable to note positive photopatch tests to other unexpected and non-relevant allergens, including fentichlor (67%), tetrachlorosalicylanilide (28%), triclosan (17%), tribromsalan (11%) and bithionol (11%), with no clinical relevance. Interestingly, these agents belong to the family of halogenated salicylanilides and related compounds, which have been forbidden in Europe since the 1970s. Our results raise the question of hyper-photosusceptibility to non-relevant allergens induced by photosensitivity to ketoprofen. The mechanism may involve the high photoreactivity induced by the association of a benzene ring with an oxygen group.

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Section: Discussionmentioning

confidence: 99%

Spectrum of cross‐photosensitization in 18 consecutive patients with contact photoallergy to ketoprofen: associated photoallergies to non‐benzophenone‐containing molecules

et al. 2003

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“…Smith and Epstein (1977) photopatch tested 352 subjects because they had a history suggestive of photosensitivity or an eruption involving sun-exposed areas. Most of the subjects with a positive photopatch test were in their fifth to sixth decade of life and none were children.…”

Section: Phototoxicitymentioning

confidence: 99%

Safety Assessment of Dichlorophene and Chlorophene1

Yamarik¹

2004

Int J Toxicol

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Dichlorophene is a halogenated phenolic compound that functions as a bacteriocide and fungicide in cosmetics. Chlorophene is a halogenated phenolic compound that functions as a biocide and preservative in cosmetics. Dichlorophene was reported to be used in a total of five cosmetic formulations at concentrations of 0% to 1.0%, but Chlorophene was not reported to be used. Dichlorophene is prohibited for use in cosmetic ingredients in Japan. In Europe, the maximum authorized concentration allowed for Dichlorophene is 0.5% and for Chlorophene is 0.2%. The major impurity of Dichlorophene is the trimer 4-chloro-2,6-bis(5-chloro-2-hydroxy-benzyl)phenol. In rats, Dichlorophene sulfate, Dichlorophene monoglucuronide, and Dichlorophene diglucuronide were the major metabolites of Dichlorophene and were excreted, mainly in the urine. The glucuronic acid conjugate, the sulfate ester conjugate, and two minor metabolites of Chlorophene were the metabolites found in rat urine. Chlorophene was incompletely absorbed through the rat skin. These chemicals exhibited low toxicity in acute oral toxicity studies in several animal species. Some evidence of toxicity with both chemicals was found in short-term oral toxicity studies in mice and rats; nephropathy was the principal finding. Chronic toxicity data were not available for Dichlorophene. Rats and mice dosed with Chlorophene for 2 years had a dose-related and sex-related increase in the severity of nephropathy. In animal tests, Dichlorophene and Chlorophene were ocular irritants. No inhalation toxicity data were available for these ingredients. Dichlorophene up to 10% concentration resulted in no to minimal irritation when applied to the intact and abraded skin of rabbits. Chlorophene was severely irritating to rabbits in most dermal irritation studies. Studies on guinea pigs gave positive and negative results in sensitization tests of Dichlorophene. A dose-related contact hypersensitivity response to Chlorophene was reported in mice. No reproductive or developmental toxicity data were available for Dichlorophene, but there was some evidence of non-dose-dependent developmental toxicity with Chlorophene in rabbits. Dichlorophene was positive in the Ames mutagenicity assay, but not in mammalian or fruit fly test systems. Chlorophene was mutagenic in four in vitro mammalian test systems. Carcinogenicity studies for Dichlorophene were not found. Neoplasms were not observed in rats treated with Chlorophene for 2 years; however a significant incidence of neoplasms was observed in mice so treated. A 1-year National Toxicology Program (NTP) study concluded that Chlorophene was a cutaneous irritant and a weak skin tumor promoter but had no activity as an initiator or complete carcinogen. Dichlorophene was not a sensitizer in clinical dermal sensitization tests. Some reactions to Chlorophene occurred in some, but not all, clinical dermal sensitization tests. Positive photopatch tests to Dichlorophene were found in 13/469 patients. Although these ingredients were ocular irritants at high concentrations, the risk at concentrations which are actually used in cosmetic formulations was uncertain. Overall, the available data were insufficient to support safety of Dichlorophene or Chlorophene. Additional data needed include (1) method of manufacture and impurities data (especially the trimer in Dichlorophene); (2) photosensitization and photo-carcinogenicity data for Dichlorophene; (3) dermal reproductive and developmental toxicity data for Dichlorophene (as a function of dose); and (4) ocular irritation at concentration of use, if available.

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