PMID- 24333256
OWN - NLM
STAT- MEDLINE
DCOM- 20140321
LR  - 20190116
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 274
IP  - 3
DP  - 2014 Feb 1
TI  - Introduction of a methoxymethyl side chain into p-phenylenediamine attenuates its 
      sensitizing potency and reduces the risk of allergy induction.
PG  - 480-7
LID - S0041-008X(13)00536-X [pii]
LID - 10.1016/j.taap.2013.11.016 [doi]
AB  - 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.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Goebel, Carsten
AU  - Goebel C
AD  - The Procter & Gamble Co., Central Product Safety and Communications, Darmstadt, 
      Germany. Electronic address: goebel.c.1@pg.com.
FAU - Troutman, John
AU  - Troutman J
AD  - The Procter & Gamble Co., Central Product Safety, Cincinnati, OH, USA.
FAU - Hennen, Jenny
AU  - Hennen J
AD  - Dept. of Environmental Toxicology, Trier University, Trier, Germany.
FAU - Rothe, Helga
AU  - Rothe H
AD  - The Procter & Gamble Co., Central Product Safety and Communications, Darmstadt, 
      Germany.
FAU - Schlatter, Harald
AU  - Schlatter H
AD  - The Procter & Gamble Co., Central Product Safety and Communications, Darmstadt, 
      Germany.
FAU - Gerberick, G Frank
AU  - Gerberick GF
AD  - The Procter & Gamble Co., Central Product Safety, Cincinnati, OH, USA.
FAU - Blomeke, Brunhilde
AU  - Blomeke B
AD  - Dept. of Environmental Toxicology, Trier University, Trier, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131210
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (B7-2 Antigen)
RN  - 0 (Hair Dyes)
RN  - 0 (Phenylenediamines)
RN  - 5982W4U40M (2-methoxymethyl-p-phenylenediamine)
RN  - U770QIT64J (4-phenylenediamine)
SB  - IM
MH  - Animals
MH  - B7-2 Antigen/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Dendritic Cells/cytology/drug effects/immunology
MH  - Dermatitis, Allergic Contact/immunology/*prevention & control
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Hair Dyes/chemistry/*toxicity
MH  - Humans
MH  - Local Lymph Node Assay
MH  - Lymph Nodes/drug effects/immunology
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Phenylenediamines/chemistry/*pharmacology/*toxicity
MH  - Risk Assessment
MH  - Skin/drug effects/immunology
OTO - NOTNLM
OT  - 2,4-dinitrochlorobenzene
OT  - 2-Methoxymethyl-p-phenylenediamine
OT  - 2-methoxymethyl-p-phenylenediamine
OT  - Alternative methods
OT  - DC
OT  - DMSO
OT  - DNCB
OT  - HE-PPD
OT  - HRP/P
OT  - Hair dyes
OT  - Innate immune response
OT  - LLNA
OT  - ME-PPD
OT  - MEL
OT  - NESIL
OT  - PPD
OT  - PTD
OT  - QRA
OT  - SCCS
OT  - SI
OT  - Scientific Committee on Consumer Safety
OT  - Skin metabolism
OT  - Skin sensitization
OT  - WoE
OT  - dendritic cell
OT  - dimethylsulfoxide
OT  - horseradish peroxidase and hydrogen peroxide
OT  - hydroxyethyl-PPD
OT  - local lymph node assay
OT  - measured exposure level
OT  - no expected sensitization induction level
OT  - p-phenylenediamine
OT  - p-toluylenediamine
OT  - quantitative risk assessment
OT  - stimulation index
OT  - weight-of-evidence
EDAT- 2013/12/18 06:00
MHDA- 2014/03/22 06:00
CRDT- 2013/12/17 06:00
PHST- 2013/09/04 00:00 [received]
PHST- 2013/11/04 00:00 [revised]
PHST- 2013/11/26 00:00 [accepted]
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/03/22 06:00 [medline]
AID - S0041-008X(13)00536-X [pii]
AID - 10.1016/j.taap.2013.11.016 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2014 Feb 1;274(3):480-7. doi: 10.1016/j.taap.2013.11.016. 
      Epub 2013 Dec 10.