Introduction of a methoxymethyl side chain into p-phenylenediamine attenuates its sensitizing potency and reduces the risk of allergy induction.

Abstract

The strong sensitizing potencies of the most important primary intermediates of oxidative hair dyes, p-phenylenediamine (PPD) and p-toluylenediamine (PTD, i.e. 2-methyl-PPD) are well established. They are considered as the key sensitizers in hair dye allergic contact dermatitis. While modification of their molecular structure is expected to alter their sensitizing properties, it may also impair their color performance. With introduction of a methoxymethyl side chain we found the primary intermediate 2-methoxymethyl-p-phenylenediamine (ME-PPD) with excellent hair coloring performance but significantly reduced sensitizing properties compared to PPD and PTD: In vitro, ME-PPD showed an attenuated innate immune response when analyzed for its protein reactivity and dendritic cell activation potential. In vivo, the effective concentration of ME-PPD necessary to induce an immune response 3-fold above vehicle control (EC3 value) in the local lymph node assay (LLNA) was 4.3%, indicating a moderate skin sensitizing potency compared to values of 0.1 and 0.17% for PPD and PTD, respectively. Finally, assessing the skin sensitizing potency of ME-PPD under consumer hair dye usage conditions through a quantitative risk assessment (QRA) indicated an allergy induction risk negligible compared to PPD or PTD.

• Authors: Carsten Goebel, John Troutman, Jenny Hennen, Helga Rothe, Harald Schlatter, G Frank Gerberick, Brunhilde Blömeke
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 274 Issue 3 Pg. 480-7 (Feb 01 2014) ISSN: 1096-0333 [Electronic] United States
• PMID: 24333256 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• B7-2 Antigen
• Hair Dyes
• Phenylenediamines
• 2-methoxymethyl-p-phenylenediamine
• 4-phenylenediamine

Topics

• Animals
• B7-2 Antigen (genetics, metabolism)
• Cell Line, Tumor
• Dendritic Cells (cytology, drug effects, immunology)
• Dermatitis, Allergic Contact (immunology, prevention & control)
• Dose-Response Relationship, Drug
• Female
• Hair Dyes (chemistry, toxicity)
• Humans
• Local Lymph Node Assay
• Lymph Nodes (drug effects, immunology)
• Mice
• Mice, Inbred CBA
• Phenylenediamines (chemistry, pharmacology, toxicity)
• Risk Assessment
• Skin (drug effects, immunology)