PMID- 17467128
OWN - NLM
STAT- MEDLINE
DCOM- 20071011
LR  - 20191210
IS  - 0273-2300 (Print)
IS  - 0273-2300 (Linking)
VI  - 48
IP  - 2
DP  - 2007 Jul
TI  - TIMES-SS--a promising tool for the assessment of skin sensitization hazard. A 
      characterization with respect to the OECD validation principles for (Q)SARs and 
      an external evaluation for predictivity.
PG  - 225-39
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 comprising industry and regulators. The 
      model was developed with the aim of minimizing animal testing and to be 
      scientifically valid in accordance with the OECD principles for (Q)SAR 
      validation. TIMES-SS encodes structure-toxicity and structure-skin metabolism 
      relationships through a number of transformations, some of which are underpinned 
      by mechanistic 3D QSARs. Here, we describe the extent to which the five OECD 
      principles are met and in particular the results from an external evaluation 
      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. 
      Further evaluation of these results highlighted certain inconsistencies which 
      were rationalized by a consideration of reaction chemistry principles for 
      sensitization. Improvements for TIMES-SS were proposed where appropriate. 
      TIMES-SS is a promising tool to aid in the evaluation of skin sensitization 
      hazard under legislative programs such as REACH.
FAU - Patlewicz, Grace
AU  - Patlewicz G
AD  - European Chemicals Bureau, TP 582, Institute for Health and Consumer Protection, 
      Joint Research Centre, European Commission, 21020 Ispra, VA, Italy. 
      grace.patlewicz@jrc.it
FAU - Dimitrov, Sabcho D
AU  - Dimitrov SD
FAU - Low, Lawrence K
AU  - Low LK
FAU - Kern, Petra S
AU  - Kern PS
FAU - Dimitrova, Gergana D
AU  - Dimitrova GD
FAU - Comber, Mike I H
AU  - Comber MI
FAU - Aptula, Aynur O
AU  - Aptula AO
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 - Roberts, David W
AU  - Roberts DW
FAU - Bailey, Paul T
AU  - Bailey PT
FAU - Mekenyan, Ovanes G
AU  - Mekenyan OG
LA  - eng
PT  - Journal Article
PT  - Validation Study
DEP - 20070325
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Irritants)
SB  - IM
MH  - Animal Testing Alternatives/*methods
MH  - Animals
MH  - Computer Simulation
MH  - European Union
MH  - Irritants/*chemistry
MH  - Local Lymph Node Assay
MH  - Mice
MH  - *Models, Chemical
MH  - *Quantitative Structure-Activity Relationship
MH  - Risk Assessment
MH  - Skin/drug effects
MH  - Skin Irritancy Tests/methods
EDAT- 2007/05/01 09:00
MHDA- 2007/10/12 09:00
CRDT- 2007/05/01 09:00
PHST- 2007/02/02 00:00 [received]
PHST- 2007/05/01 09:00 [pubmed]
PHST- 2007/10/12 09:00 [medline]
PHST- 2007/05/01 09:00 [entrez]
AID - S0273-2300(07)00039-6 [pii]
AID - 10.1016/j.yrtph.2007.03.003 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2007 Jul;48(2):225-39. doi: 10.1016/j.yrtph.2007.03.003. 
      Epub 2007 Mar 25.