title: Methylisothiazolinone in rinse-off products causes allergic contact dermatitis: a repeated open-application study.
abstract: BACKGROUND
  In recent years, the prevalence of contact allergy to the preservative methylisothiazolinone (MI) has increased dramatically. Cosmetic products are one of the major sources of exposure.
  
  
  OBJECTIVE
  To examine whether allowed concentrations of MI in cosmetic rinse-off products have the potential to cause allergic contact dermatitis.
  
  
  METHODS
  Nineteen MI-allergic subjects and 19 controls without MI allergy applied two liquid hand soaps five times per day on areas of 5 × 10 cm(2) on the ventral side of their forearms. One soap contained 100 ppm MI, the maximum allowed concentration in cosmetics, and was used by 10 allergic subjects and all controls. Another liquid soap with 50 ppm MI was used by nine allergic subjects. As the negative control, all subjects used a similar soap that did not contain MI. The repeated open applications proceeded until a positive reaction occurred or up to 21 days. The study was conducted in a randomized and blinded fashion.
  
  
  RESULTS
  Ten out of 10 MI-allergic subjects developed positive reactions to the soap with 100 ppm and seven out of nine reacted to the 50 ppm soap, while none of the 19 controls had a positive reaction during 21 days of application. No reactivity was seen to the soap without MI. The difference in reactivity to MI between MI-allergic subjects and controls was statistically significant (Fisher's exact test, P ˂ 0.0001).
  
  
  CONCLUSIONS
  Rinse-off products preserved with 50 ppm MI or more are not safe for consumers. No safe level has yet been identified.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-17177, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Yazar
authors.affiliation: Department of Dermato-Allergology, National Allergy Research Centre, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
authors.forename: M D
authors.initials: MD
authors.lastname: Lundov
authors.affiliation: Department of Dermato-Allergology, National Allergy Research Centre, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Faurschou
authors.affiliation: Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Matura
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-17177, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Boman
authors.affiliation: Department of Dermato-Allergology, National Allergy Research Centre, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
authors.forename: J D
authors.initials: JD
authors.lastname: Johansen
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-17177, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Lidén
mesh_terms: D000328:Adult; D003358:Cosmetics / Q000009:adverse effects*; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D006801:Humans; D008452:Maximum Allowable Concentration; D008875:Middle Aged; D010328:Patch Tests; D012915:Soaps / Q000009:adverse effects*; D013844:Thiazoles / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D003358:Cosmetics; D012915:Soaps; D013844:Thiazoles; C011506:2-methyl-4-isothiazolin-3-one