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Merck

Methylisothiazolinone contact allergy and dose-response relationships.

Contact dermatitis (2011-04-21)
Michael D Lundov, Claus Zachariae, Jeanne D Johansen
ABSTRACT

Methylisothiazolinone (MI) used alone is a new preservative causing a high prevalence of contact allergy. The eliciting threshold of MI is unknown. The combination of MI and phenoxyethanol enhances the antimicrobial efficacy of MI. The eliciting doses of MI contact allergy in a patch test and a repeated open application test (ROAT) were investigated. In the patch test, it was determined whether phenoxyethanol influenced the reactivity to MI. Eleven MI-allergic individuals were patch tested with two dilution series of 12 doses of MI and the same 12 doses with phenoxyethanol. The ROAT mimicked the use of a cream preserved with 100, 50 and 5 ppm MI (corresponding to 0.21, 0.105 and 0.0105 µg MI/cm(2)). Phenoxyethanol had no influence on the reactions to MI. The lowest eliciting dose in the patch test was 1.47 µg MI/cm(2). In the ROAT, 7 patients (64%) reacted to 0.21 and 0.105 µg MI/cm(2) and 2 patients (18%) reacted to 0.0105 µg MI/cm(2), corresponding to a cream preserved with 5 ppm MI. A maximum of 100 ppm MI is permitted in cosmetic products. Eighteen per cent of MI-allergic patients reacted to a concentration 20 times lower in a ROAT. The amounts used in cosmetics should be reduced, and the development of MI contact allergy should be monitored closely.

MATERIALS
Product Number
Brand
Product Description

Supelco
2-Phenoxyethanol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
2-Phenoxyethanol, ≥99%
Supelco
2-Phenoxyethanol, analytical standard
Sigma-Aldrich
2-Methyl-4-isothiazolin-3-one hydrochloride, ≥99%
Sigma-Aldrich
2-Methyl-4-isothiazolin-3-one, 95%
Sigma-Aldrich
Ethylene glycol monophenyl ether, ≥90%
Supelco
2-Methyl-4-isothiazolin-3-one, analytical standard