TIMES-SS - A Mechanistic Evaluation of an External Validation Study Using Reaction Chemistry Principles

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. 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 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 4 chemicals was carried out to explore some of the 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 hazard under legislative programs such as REACH.

ROBERTS Dw;  TIER Grace;  DIMITROV S;  LOW L;  APTULA Ao;  KERN Petra;  DIMITROVA G;  COMBER M;  PHILLIPS R;  NIEMELA J;  MADSEN Charlotte;  WEDEBYE Eb;  BAILEY P;  MEKENYAN O; 

2007-11-23

AMER CHEMICAL SOC

JRC37447

0893-228X,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC37447,   

10.1021/tx700169w,