PMID- 25000333
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20140729
IS  - 1547-6898 (Electronic)
IS  - 1040-8444 (Linking)
VI  - 44
IP  - 7
DP  - 2014 Aug
TI  - Anchoring molecular mechanisms to the adverse outcome pathway for skin 
      sensitization: Analysis of existing data.
PG  - 590-9
LID - 10.3109/10408444.2014.925425 [doi]
AB  - Allergic contact dermatitis (ACD) is a hypersensitivity immune response induced 
      by small protein-reactive chemicals. Currently, the murine local lymph node assay 
      (LLNA) provides hazard identification and quantitative estimation of sensitizing 
      potency. Given the complexity of ACD, a single alternative method cannot replace 
      the LLNA, but it is necessary to combine methods through an integrated testing 
      strategy (ITS). In the development of an ITS, information regarding mechanisms 
      and molecular processes involved in skin sensitization is crucial. The recently 
      published adverse outcome pathway (AOP) for skin sensitization captures 
      mechanistic knowledge into key events that lead to ACD. To understand the 
      molecular processes in ACD, a systematic review of murine in vivo studies was 
      performed and an ACD molecular map was constructed. In addition, comparing the 
      molecular map to the limited human in vivo toxicogenomic data available suggests 
      that certain processes are similarly triggered in mice and humans, but additional 
      human data will be needed to confirm these findings and identify differences. To 
      gain insight in the molecular mechanisms represented by various human in vitro 
      systems, the map was compared to in vitro toxicogenomic data. This analysis 
      allows for comparison of emerging in vitro methods on a molecular basis, in 
      addition to mathematical predictive value. Finally, a survey of the current in 
      silico, in chemico, and in vitro methods was used to indicate which AOP key event 
      is modeled by each method. By anchoring emerging classification methods to the 
      AOP and the ACD molecular map, complementing methods can be identified, which 
      provides a cornerstone for the development of a testing strategy that accurately 
      reflects the key events in skin sensitization.
FAU - van der Veen, Jochem W
AU  - van der Veen JW
AD  - National Institute for Public Health and the Environment (RIVM), Centre for 
      Health Protection , Bilthoven , The Netherlands.
FAU - Soeteman-Hernandez, Lya G
AU  - Soeteman-Hernandez LG
FAU - Ezendam, Janine
AU  - Ezendam J
FAU - Stierum, Rob
AU  - Stierum R
FAU - Kuper, Frieke C
AU  - Kuper FC
FAU - van Loveren, Henk
AU  - van Loveren H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140707
PL  - England
TA  - Crit Rev Toxicol
JT  - Critical reviews in toxicology
JID - 8914275
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Animals
MH  - Cell Movement
MH  - Dendritic Cells/immunology/physiology
MH  - Dermatitis, Allergic Contact/*etiology
MH  - Humans
MH  - Lymphocyte Activation
MH  - Mice
MH  - NF-E2-Related Factor 2/physiology
MH  - Toll-Like Receptors/physiology
MH  - Toxicogenetics
OTO - NOTNLM
OT  - adverse outcome pathway
OT  - allergic contact dermatitis
OT  - human in vitro systems
OT  - mechanisms of toxicity
OT  - molecular map
OT  - skin sensitization
EDAT- 2014/07/08 06:00
MHDA- 2015/05/12 06:00
CRDT- 2014/07/08 06:00
PHST- 2014/07/08 06:00 [entrez]
PHST- 2014/07/08 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
AID - 10.3109/10408444.2014.925425 [doi]
PST - ppublish
SO  - Crit Rev Toxicol. 2014 Aug;44(7):590-9. doi: 10.3109/10408444.2014.925425. Epub 
      2014 Jul 7.