Cross-reactivity between methylisothiazolinone, octylisothiazolinone and benzisothiazolinone using a modified local lymph node assay

Br J Dermatol. 2017 Jan;176(1):176-183. doi: 10.1111/bjd.14825. Epub 2016 Nov 26.

Abstract

Background: In the light of the exceptionally high rates of contact allergy to the preservative methylisothiazolinone (MI), information about cross-reactivity between MI, octylisothiazolinone (OIT) and benzisothiazolinone (BIT) is needed.

Objectives: To study cross-reactivity between MI and OIT, and between MI and BIT.

Methods: Immune responses to MI, OIT and BIT were studied in vehicle and MI-sensitized female CBA mice by a modified local lymph node assay. The inflammatory response was measured by ear thickness, cell proliferation of CD4+ and CD8+ T cells, and CD19+ B cells in the auricular draining lymph nodes.

Results: MI induced significant, strong, concentration-dependent immune responses in the draining lymph nodes following a sensitization phase of three consecutive days. Groups of MI-sensitized mice were challenged on day 23 with 0·4% MI, 0·7% OIT and 1·9% BIT - concentrations corresponding to their individual EC3 values. No statistically significant difference in proliferation of CD4+ and CD8+ T cells was observed between mice challenged with MI compared with mice challenged with BIT and OIT.

Conclusions: The data indicate cross-reactivity between MI, OIT and BIT, when the potency of the chemical was taken into account in choice of challenge concentration. This means that MI-sensitized individuals may react to OIT and BIT if exposed to sufficient concentrations.

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation / drug effects
  • Disinfectants / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Ear, External / drug effects
  • Female
  • Immunity, Cellular / physiology
  • Local Lymph Node Assay
  • Lymph Nodes / drug effects*
  • Lymph Nodes / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred CBA
  • Thiazoles / administration & dosage
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Disinfectants
  • Thiazoles
  • isothiazolidinone
  • 2-methyl-4-isothiazolin-3-one
  • 1,2-benzisothiazoline-3-one