title: In situ chemical behaviour of methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI) in reconstructed human epidermis: a new approach to the cross-reactivity issue.
abstract: BACKGROUND
  Methylisothiazolinone (MI) [with methylchloroisothiazolinone (MCI) in a ratio of 1:3, a well-recognized allergenic preservative] was released as an individual preservative in the 2000s for industrial products and in 2005 for cosmetics. The high level of exposure to MI since then has provoked an epidemic of contact allergy to MI, and an increase in MI/MCI allergy. There are questions concerning the MI/MCI cross-reaction pattern.
  
  
  OBJECTIVE
  To bring a new perspective on the MI/MCI cross-reactivity issue by studying their in situ chemical behaviour in 3D reconstructed human epidermis (RHE).
  
  
  METHODS
  MI and MCI were synthesized with (13) C substitution at positions C-4/C-5 and C-5, respectively. Their in situ chemical behaviours in an RHE model were followed by use of the high-resolution magic angle spinning nuclear magnetic resonance technique.
  
  
  RESULTS
  MI was found to react exclusively with cysteine thiol residues, whereas MCI reacted with histidines and lysines. The reaction mechanisms were found to be different for MI and MCI, and the adducts formed had different molecular structures.
  
  
  CONCLUSIONS
  In RHE, different MI/MCI reactions towards different nucleophilic amino acids were observed, making it difficult to explain cross-reactivity between MI and MCI.
authors.affiliation: Dermatochemistry Laboratory, Institut de Chimie de Strasbourg, UMR 7177/Université de Strasbourg - CNRS, 67081, Strasbourg, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Debeuckelaere
authors.affiliation: Dermatochemistry Laboratory, Institut de Chimie de Strasbourg, UMR 7177/Université de Strasbourg - CNRS, 67081, Strasbourg, France.|Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), UMR 7357/Université de Strasbourg - CNRS, 674012, Illkirch, France.
authors.forename: François-Marie
authors.initials: FM
authors.lastname: Moussallieh
authors.affiliation: Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), UMR 7357/Université de Strasbourg - CNRS, 674012, Illkirch, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Elbayed
authors.affiliation: Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), UMR 7357/Université de Strasbourg - CNRS, 674012, Illkirch, France.
authors.forename: Izzie-Jacques
authors.initials: IJ
authors.lastname: Namer
authors.affiliation: Dermatochemistry Laboratory, Institut de Chimie de Strasbourg, UMR 7177/Université de Strasbourg - CNRS, 67081, Strasbourg, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Berl
authors.affiliation: Dermatochemistry Laboratory, Institut de Chimie de Strasbourg, UMR 7177/Université de Strasbourg - CNRS, 67081, Strasbourg, France.
authors.forename: Elena
authors.initials: E
authors.lastname: Giménez-Arnau
authors.affiliation: Dermatochemistry Laboratory, Institut de Chimie de Strasbourg, UMR 7177/Université de Strasbourg - CNRS, 67081, Strasbourg, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lepoittevin
mesh_terms: D003429:Cross Reactions; D003545:Cysteine / Q000737:chemistry; D004817:Epidermis / Q000737:chemistry*; D006639:Histidine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry* / Q000276:immunology
chemical_list: D013438:Sulfhydryl Compounds; D013844:Thiazoles; C011506:2-methyl-4-isothiazolin-3-one; D006639:Histidine; C011421:5-chloro-2-methyl-4-isothiazolin-3-one; D008239:Lysine; D003545:Cysteine
keywords: CAS no. 26172-55-4; CAS no. 2682-20-4; HRMAS NMR; cross-reactivity; methylchloroisothiazolinone; methylisothiazolinone; reaction chemistry; reconstructed human epidermis