News

I. Modifications in the platform

 

• Documented Metabolism database version is updated from 3.4.2 to 3.4.3 (compatible with MetaPath version 5.4.3).

  Docking with OECD QSAR Toolbox ver.4.8.

 

 

II. Modifications in the models, existing and new functionalities

 

• Modifications in the non-kinetic genotoxicity models:

   o Addition of new documented maps is performed for in vitro and in vivo metabolism databases.
   o Modifications are done in the in vitro S9 and in vivo rat metabolic simulators to improve their predictive capabilities.
   o Modifications in DNA binding N-Nitrosamine’s alert is performed to address mutagenicity of parents and metabolites simultaneously.
 

• Modifications in the kinetic genotoxicity models:

   o The modifications done in the non-kinetic models related to the update of alert definition, metabolic transformations and databases with documented metabolism are transferred to the respective kinetic models. 
   o In the current version of Ames kinetic model, the kinetic approach for calculating quantities of simulated metabolites is taken into account to resolve some limitations of the probabilistic approach (used in the previous version of the model). It is developed based on the following principles:
     - The first order kinetic is assumed for the kinetic curves describing the metabolic transformations;
     - The functions for calculating quantities of parallel transformations are re-derived from well-known differential equations.

•  Modifications in the non-kinetic skin sensitization models:

   o Enzymatic information is provided in the transformation tables of all skin sensitization models.

• Modifications in the kinetic skin sensitization model:

   o Four additional P-Groups are included to resolve some technical problems identified with the model.

• Report of metabolites' quantities over the time is a new functionality, implemented for all kinetic models available in the TIMES software. It allows to report the quantity of all simulated metabolites as a function of time.

 

• Enzyme report button is implemented for models where enzyme information is available.

 

• Exact mass calculation of parent molecules and simulated metabolites is provided and could be included in the reports (e.g., full report, QPRF, etc.). It is developed as a new 2D parameter allowing to calculate the exact mass of the chemicals considering the mass of the most stable and longest-lived isotopes.

 

• Improvements of the QPRF:

   o Filtering the analogues supporting prediction with the profilers available in QSAR Toolbox. Reporting the obtained results.
   o Modifications of the report allowing to omit the empty fields that are not filled in by the user.
 

• Improvements related to QAF protocol: 

   o Transfer TIMES predictions generated in Toolbox to IUCLID.
   o Automatically fulfilled fields in IUCLID (through Toolbox).
   o Transfer QPRF from the TIMES model to IUCLID (as an attachment).