PMID- 17713962
OWN - NLM
STAT- MEDLINE
DCOM- 20071211
LR  - 20220311
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 20
IP  - 9
DP  - 2007 Sep
TI  - TIMES-SS--a mechanistic evaluation of an external validation study using reaction 
      chemistry principles.
PG  - 1321-30
AB  - The TImes MEtabolism Simulator platform used for predicting skin sensitization 
      (TIMES-SS) is a hybrid expert system that was developed at Bourgas University 
      using funding and data from a consortium comprised of industry and regulators. 
      TIMES-SS encodes structure-toxicity and structure-skin metabolism relationships 
      through a number of transformations, some of which are underpinned by mechanistic 
      three-dimensional quantitative structure-activity relationships. Here, we 
      describe an external validation exercise that was recently carried out. As part 
      of this exercise, data were generated for 40 new chemicals in the murine local 
      lymph node assay (LLNA) and then compared with predictions made by TIMES-SS. The 
      results were promising with an overall good concordance (83%) between 
      experimental and predicted values. The LLNA results were evaluated with respect 
      to reaction chemistry principles for sensitization. Additional testing on a 
      further four chemicals was carried out to explore some of the specific reaction 
      chemistry findings in more detail. Improvements for TIMES-SS, where appropriate, 
      were put forward together with proposals for further research work. TIMES-SS is a 
      promising tool to aid in the evaluation of skin sensitization potential under 
      legislative programs such as REACH.
FAU - Roberts, David W
AU  - Roberts DW
AD  - Liverpool John Moores University, Liverpool, United Kingdom.
FAU - Patlewicz, Grace
AU  - Patlewicz G
FAU - Dimitrov, Sabcho D
AU  - Dimitrov SD
FAU - Low, Lawrence K
AU  - Low LK
FAU - Aptula, Aynur O
AU  - Aptula AO
FAU - Kern, Petra S
AU  - Kern PS
FAU - Dimitrova, Gergana D
AU  - Dimitrova GD
FAU - Comber, Mike I H
AU  - Comber MI
FAU - Phillips, Richard D
AU  - Phillips RD
FAU - Niemela, Jay
AU  - Niemela J
FAU - Madsen, Charlotte
AU  - Madsen C
FAU - Wedebye, Eva B
AU  - Wedebye EB
FAU - Bailey, Paul T
AU  - Bailey PT
FAU - Mekenyan, Ovanes G
AU  - Mekenyan OG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Validation Study
DEP - 20070823
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Acetates)
RN  - 0 (Allyl Compounds)
RN  - 0 (Drug Combinations)
RN  - 0 (Irritants)
RN  - 0 (Peroxides)
RN  - 31PZ2VAU81 (Carbamide Peroxide)
RN  - 8W8T17847W (Urea)
RN  - E4U5E5990I (allyl acetate)
SB  - IM
MH  - Acetates/chemistry
MH  - Allyl Compounds/chemistry
MH  - Animal Testing Alternatives/*methods
MH  - Animals
MH  - Carbamide Peroxide
MH  - Drug Combinations
MH  - Irritants/*chemistry
MH  - Local Lymph Node Assay
MH  - *Models, Chemical
MH  - Molecular Structure
MH  - Peroxides
MH  - *Quantitative Structure-Activity Relationship
MH  - Skin Irritancy Tests/*methods
MH  - Toxicity Tests/methods/trends
MH  - Urea/analogs & derivatives
EDAT- 2007/08/24 09:00
MHDA- 2007/12/12 09:00
CRDT- 2007/08/24 09:00
PHST- 2007/08/24 09:00 [pubmed]
PHST- 2007/12/12 09:00 [medline]
PHST- 2007/08/24 09:00 [entrez]
AID - 10.1021/tx700169w [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2007 Sep;20(9):1321-30. doi: 10.1021/tx700169w. Epub 2007 Aug 
      23.