title: TIMES-SS--a mechanistic evaluation of an external validation study using reaction chemistry principles.
abstract: 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.
authors: Liverpool John Moores University, Liverpool, United Kingdom.
authors: David W
authors: DW
authors: Roberts
authors: Grace
authors: G
authors: Patlewicz
authors: Sabcho D
authors: SD
authors: Dimitrov
authors: Lawrence K
authors: LK
authors: Low
authors: Aynur O
authors: AO
authors: Aptula
authors: Petra S
authors: PS
authors: Kern
authors: Gergana D
authors: GD
authors: Dimitrova
authors: Mike I H
authors: MI
authors: Comber
authors: Richard D
authors: RD
authors: Phillips
authors: Jay
authors: J
authors: Niemelä
authors: Charlotte
authors: C
authors: Madsen
authors: Eva B
authors: EB
authors: Wedebye
authors: Paul T
authors: PT
authors: Bailey
authors: Ovanes G
authors: OG
authors: Mekenyan
mesh_terms: D000085:Acetates / Q000737:chemistry; D000498:Allyl Compounds / Q000737:chemistry; D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D000077463:Carbamide Peroxide; D004338:Drug Combinations; D007509:Irritants / Q000737:chemistry*; D023441:Local Lymph Node Assay; D008956:Models, Chemical; D015394:Molecular Structure; D010545:Peroxides; D021281:Quantitative Structure-Activity Relationship; D023422:Skin Irritancy Tests / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods / Q000639:trends; D014508:Urea / Q000031:analogs & derivatives
chemical_list: D000085:Acetates; D000498:Allyl Compounds; D004338:Drug Combinations; D007509:Irritants; D010545:Peroxides; D000077463:Carbamide Peroxide; D014508:Urea; C498551:allyl acetate