PMID- 18832184
OWN - NLM
STAT- MEDLINE
DCOM- 20090807
LR  - 20220311
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 107
IP  - 1
DP  - 2009 Jan
TI  - Filling the concept with data: integrating data from different in vitro and in 
      silico assays on skin sensitizers to explore the battery approach for animal-free 
      skin sensitization testing.
PG  - 106-21
LID - 10.1093/toxsci/kfn204 [doi]
AB  - Tests for skin sensitization are required prior to the market launch of new 
      cosmetic ingredients. Significant efforts are made to replace the current animal 
      tests. It is widely recognized that this cannot be accomplished with a single in 
      vitro test, but that rather the integration of results from different in vitro 
      and in silico assays will be needed for the prediction of the skin sensitization 
      potential of chemicals. This has been proposed as a theoretical scheme so far, 
      but no attempts have been made to use experimental data to prove the validity of 
      this concept. Here we thus try for the first time to fill this widely cited 
      concept with data. To this aim, we integrate and report both novel and literature 
      data on 116 chemicals of known skin sensitization potential on the following 
      parameters: (1) peptide reactivity as a surrogate for protein binding, (2) 
      induction of antioxidant/electrophile responsive element dependent luciferase 
      activity as a cell-based assay; (3) Tissue Metabolism Simulator skin 
      sensitization model in silico prediction; and (4) calculated octanol-water 
      partition coefficient. The results of the in vitro assays were scaled into five 
      classes from 0 to 4 to give an in vitro score and compared to the local lymph 
      node assay (LLNA) data, which were also scaled from 0 to 4 
      (nonsensitizer/weak/moderate/strong/extreme). Different ways of evaluating these 
      data have been assessed to rate the hazard of chemicals (Cooper statistics) and 
      to also scale their potency. With the optimized model an overall accuracy for 
      predicting sensitizers of 87.9% was obtained. There is a linear correlation 
      between the LLNA score and the in vitro score. However, the correlation needs 
      further improvement as there is still a relatively high variation in the in vitro 
      score between chemicals belonging to the same sensitization potency class.
FAU - Natsch, Andreas
AU  - Natsch A
AD  - Givaudan Schweiz AG, CH-8600 Duebendorf, Switzerland.
FAU - Emter, Roger
AU  - Emter R
FAU - Ellis, Graham
AU  - Ellis G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081001
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Cosmetics)
RN  - 0 (Peptides)
SB  - IM
MH  - Animal Testing Alternatives/*methods
MH  - Cell Line, Tumor
MH  - *Computer Simulation
MH  - Cosmetics/*pharmacology
MH  - Databases as Topic
MH  - Dermatitis, Allergic Contact/*metabolism
MH  - Female
MH  - Humans
MH  - Local Lymph Node Assay
MH  - Peptides/metabolism
MH  - Regression Analysis
MH  - Skin Tests/methods
MH  - Statistics, Nonparametric
EDAT- 2008/10/04 09:00
MHDA- 2009/08/08 09:00
CRDT- 2008/10/04 09:00
PHST- 2008/10/04 09:00 [entrez]
PHST- 2008/10/04 09:00 [pubmed]
PHST- 2009/08/08 09:00 [medline]
AID - kfn204 [pii]
AID - 10.1093/toxsci/kfn204 [doi]
PST - ppublish
SO  - Toxicol Sci. 2009 Jan;107(1):106-21. doi: 10.1093/toxsci/kfn204. Epub 2008 Oct 1.