title: Methylisothiazolinone contact allergy and dose-response relationships.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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)).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermato-Allergology, National Allergy Research Centre, Copenhagen University Hospital Gentofte, DK-2820 Gentofte, Denmark. midylu01@geh.regionh.dk
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lundov
authors.forename: Claus
authors.initials: C
authors.lastname: Zachariae
authors.forename: Jeanne D
authors.initials: JD
authors.lastname: Johansen
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D003358:Cosmetics / Q000009:adverse effects* / Q000592:standards; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005026:Ethylene Glycols / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D010328:Patch Tests; D011310:Preservatives, Pharmaceutical / Q000009:adverse effects*; D015203:Reproducibility of Results; D012882:Skin Tests; D013844:Thiazoles / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D003358:Cosmetics; D004338:Drug Combinations; D005026:Ethylene Glycols; D011310:Preservatives, Pharmaceutical; D013844:Thiazoles; C011506:2-methyl-4-isothiazolin-3-one; C005398:phenoxyethanol