TIMES 2.30.1

March, 2020

 TIMES 2.30.1 (March, 2020) is available for download.



The more important new features/updates in TIMES v.2.30.1 models are listed below:
I. General improvements
• Cache files with pre-caching results of generated metabolites, prediction results, etc. for the training sets of the models
• Flexible search improvements
• Possibility to compare the similarity between the simulated metabolic pathways of the chemicals
• Improvements in the QMRF and QPRF
• Additional supporting information - new help buttons
II. Models without metabolism
1. Acute Oral Toxicity LD50 24h model v.13
The acute oral toxicity model is updated with:
• 504 new training chemicals
• 13 newly defined acute toxicological categories for which expert analysis for mechanistic similarity and alert description have been done.
The AOT v13 consists of 1814 training set chemicals categorized into 73 AOT categories
2. Eye Irritation model v.06
3. Skin irritation/ corrosion model v.06
4. Acute Aquatic Toxicity models
5. Photoinduced toxicity v.03
6. Receptor-mediated models
a. Aryl hydrocarbon receptor model v.01
b. Androgen binding affinity v.03
c. Aromatase Inhibition v.01
d. Estrogen binding affinity v.04
III. Models accounting for metabolism (Kinetic)
1. Rat liver S9 metabolism Kinetics v.01.01
2. Skin metabolism kinetics v.01.01
3. Skin sensitization kinetics v. pilot
IV. Models accounting for metabolism (Non-kinetic)
1. In vitro Ames Mutagenicity v.17.17
Chemicals included in the training set of the TIMES Ames model are collected according to the recommendation in the OECD technical guideline 471 addressing the number of Salmonella typhimurium strains (TA100, TA98, TA1535, TA1537, E. coli) associated with each data.
The refined training set include 3569 chemicals (1738 of which are proprietary chemicals). The training set is including chemicals:
A. Positive as parents only (1031 of them 188 are proprietary);
B. Positive as parents and metabolites (469 of them 117 are proprietary);
C. Negative as parents and metabolites (2069 of them 1433 are proprietary).
2. In vitro Chromosomal Aberrations v.17.17
 Upgrade of the training set now including 855 compounds:
A. Positive
a. Positive as parents only (440 of them 11 are proprietary);
b. Positive as parents and metabolites (98 of them 2 are proprietary);
B. Negative (317 of them 79 are proprietary).
3. In vitro MLA Mutagenicity v.03.03
Training set of the in vitro MLA mutagenicity model is expanded from 383 to 432 compounds by adding chemicals which are observed to be positive as parents assuming that they are also positive after S9 metabolic activation.
4. In vivo Comet Genotoxicity v.12.12
Training set of the in vivo Comet genotoxicity model consists of 151 chemicals with in vivo comet data.
New in vivo metabolic simulator based on 647 metabolic pathways documented in rat liver is used.
5. In vivo Liver Clastogenicity v.09.09
Training set of the liver clastogenicity model consists of 115 chemicals with in vivo data.
6. In vivo Liver TGR mutagenicity v.08.08
Modifying the training set based on data evaluation performed by an external expert.
Definition of TGR-specific alerts justifying TGR positive data of chemicals which are negative in the Ames test.
82 "trapping" detoxification pathways, conditioning the in vivo bioavailability of parent chemicals and their metabolites, have been defined.
Modified interface of the model.
7. In vivo Micronucleus Formation v.13.13
Training set of the in vivo Micronucleus Formation model consists of 493 chemicals.
Definition of MNT-specific alerts derived from chemicals with in vitro negative and in vivo positive.
8. Estrogen binding Affinity v.04.09
New improved in vitro metabolic simulator based on observed metabolic pathways in incubation media with rodent liver microsomes or S9 fraction.
9. Skin sensitization with autoxidation v.24.29
Addition of new chemicals - the current training set consists of 886 chemicals (39 of which have proprietary skin sensitization data)