PMID- 28159477
OWN - NLM
STAT- MEDLINE
DCOM- 20170327
LR  - 20170327
IS  - 1096-0295 (Electronic)
IS  - 0273-2300 (Linking)
VI  - 85
DP  - 2017 Apr
TI  - Assessment of skin sensitization under REACH: A case report on vehicle choice in 
      the LLNA and its crucial role preventing false positive results.
PG  - 25-32
LID - S0273-2300(17)30010-7 [pii]
LID - 10.1016/j.yrtph.2017.01.010 [doi]
AB  - In the EU, chemicals with a production or import volume in quantities of one 
      metric ton per year or more have to be tested for skin sensitizing properties 
      under the REACH regulation. The murine Local Lymph Node Assay (LLNA) and its 
      modifications are widely used to fulfil the data requirement, as it is currently 
      considered the first-choice method for in vivo testing to cover this endpoint. 
      This manuscript describes a case study highlighting the importance of 
      understanding the chemistry of the test material during testing for 'skin 
      sensitization' of MCDA (mixture of 2,4- and 2,6-diamino-methylcyclohexane) with 
      particular focus on the vehicle used. While the BrdU-ELISA modification of the 
      LLNA using acetone/olive oil (AOO) as vehicle revealed expectable positive 
      results. However, the concentration control analysis unexpectedly revealed an 
      instability of MCDA in the vehicle AOO. Further studies on the reactivity showed 
      MCDA to rapidly react with AOO under formation of various imine structures, which 
      might have caused the positive LLNA result. The repetition of the LLNA using 
      propylene glycol (PG) as vehicle did not confirm the positive results of the LLNA 
      using AOO. Finally, a classification of MCDA as skin sensitizer according to the 
      Globally Harmonized System (GHS) was not justified.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Watzek, Nico
AU  - Watzek N
AD  - Product Safety Department, BASF SE, 67056 Ludwigshafen am Rhein, Germany. 
      Electronic address: nico.watzek@basf.com.
FAU - Berger, Franz
AU  - Berger F
AD  - Product Safety Department, BASF SE, 67056 Ludwigshafen am Rhein, Germany.
FAU - Kolle, Susanne Noreen
AU  - Kolle SN
AD  - Experimental Toxicology and Ecology, BASF SE, 67056 Ludwigshafen am Rhein, 
      Germany.
FAU - Kaufmann, Tanja
AU  - Kaufmann T
AD  - Experimental Toxicology and Ecology, BASF SE, 67056 Ludwigshafen am Rhein, 
      Germany.
FAU - Becker, Matthias
AU  - Becker M
AD  - Experimental Toxicology and Ecology, BASF SE, 67056 Ludwigshafen am Rhein, 
      Germany.
FAU - van Ravenzwaay, Bennard
AU  - van Ravenzwaay B
AD  - Experimental Toxicology and Ecology, BASF SE, 67056 Ludwigshafen am Rhein, 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20170131
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Allergens)
RN  - 0 (Cyclohexylamines)
RN  - 0 (Excipients)
RN  - 0 (Haptens)
RN  - 0 (Olive Oil)
RN  - 1364PS73AF (Acetone)
RN  - 6DC9Q167V3 (Propylene Glycol)
SB  - IM
MH  - Acetone/chemistry
MH  - *Allergens/chemistry/classification/toxicity
MH  - Animals
MH  - *Cyclohexylamines/chemistry/classification/toxicity
MH  - Dermatitis, Allergic Contact
MH  - Excipients/*chemistry
MH  - Female
MH  - *Haptens/chemistry/classification/toxicity
MH  - Local Lymph Node Assay
MH  - Mice, Inbred CBA
MH  - Olive Oil/chemistry
MH  - Propylene Glycol/chemistry
MH  - Sensitivity and Specificity
OTO - NOTNLM
OT  - AOO
OT  - Adverse Outcome Pathway
OT  - BrdU-ELISA
OT  - False positive results
OT  - Local Lymph Node Assay
OT  - Skin sensitization
OT  - Test substance stability in the vehicle
EDAT- 2017/02/06 06:00
MHDA- 2017/03/28 06:00
CRDT- 2017/02/05 06:00
PHST- 2016/09/28 00:00 [received]
PHST- 2017/01/03 00:00 [revised]
PHST- 2017/01/27 00:00 [accepted]
PHST- 2017/02/06 06:00 [pubmed]
PHST- 2017/03/28 06:00 [medline]
PHST- 2017/02/05 06:00 [entrez]
AID - S0273-2300(17)30010-7 [pii]
AID - 10.1016/j.yrtph.2017.01.010 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2017 Apr;85:25-32. doi: 10.1016/j.yrtph.2017.01.010. 
      Epub 2017 Jan 31.