Modifications in QSAR Toolbox v2.3

Modifications in Toolbox v2.3

1.Profiling2.Metabolism3.Databases4.Import/export5.Other modifications6.Bug fixes

22.02.2012The OECD QSAR Toolbox for Grouping Chemicals into Categories 2

Profiling

22.02.2012The OECD QSAR Toolbox for Grouping Chemicals into Categories 3

 Updated profilers

1 ECOSAR (v1.10)

2 OECD HPV Chemical Categories

3 Protein binding by OASIS4 Protein binding by OECD5 Protein Binding Potency6 DNA binding by OASIS

7 DNA binding by OECD

8 Skin irritation corrosion Inclusion rules by BfR

9 Chemical elements

 New profilers

1 Carcinogenicity (genotox and nongenotox) alerts by ISS

2 In vitro mutagenicity (Ames test) alerts by ISS

3 In vivo mutagenicity (Micronucleus) alerts by ISS

4 Organic functional groups (extended)

5 Organic functional groups (nested) (extended)

The total number of the profilers in Toolbox 2.3 is 37. Below are presented the updated and new profilers:

Profiling

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• Modifications in the updated profilers include corrections in:

some of the category names some of the structural boundaries supporting justification – help files

• Previously presented Mutagenicity/Carcinogenicity alerts by Benigni/Bossa profiler was split to Carcinogenicity (genotox and nongenotox) alerts by ISS and In vitro mutagenicity (Ames test) alerts by ISS

• Each of the extended versions of Organic functional groups and Organic functional groups (nested) is consisting of 464 categories (each of the previous versions include 227 categories)

• The “nested” version of the extended OFG profiler is derived automatically

• New category informing for Overlapping groups appears in the profiling result from the extended Organic functional groups (nested) – the user can see the groups which are overlapped in the explain form

• The previous versions of Organic functional group and Organic functional groups (nested) will be available in Toolbox 2.3 too

Metabolism

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• Documented

• Simulated

 Updated observed metabolism

1 Observed Microbial metabolism (551 maps)

 New observed metabolism

1 Observed Mammalian metabolism *

 Updated simulators

1 Skin metabolism simulator

2 Liver metabolism simulator

* Short descriptions of the newly added database with observed metabolism is presented on next slide

Metabolism

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Observed Mammalian metabolism - Metabolic pathways documented for 100 chemicals with 630 studies in different mammals are stored in a database and available in version 2.3.

Short description: The collection includes chemicals with variety of functionalities, aliphatic amines, alkyl and aryl halides, ethers, esters, carbamates, carboxylic acid esters and multifunctional compounds. In vivo and in vitro studies were used to analyze the metabolic fate of chemicals. Metabolic maps with the in vivo studies are predominantly for the collection of studies (347 studies included in 49 maps). Microsomes prevail over the other experimental systems included in the in vitro studies (around 50% of studies). Around 50% of administration routes included the in vivo studies refer to oral route of administration. Different sources including monographs, scientific articles and public web sites were used to compile the database.

Databases

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 New Databases

1 MUNRO non-cancer

2 Bacterial mutagenicity ISSSTY

3 Hydrolysis rate constant

 Updated Databases

1 Skin Sensitisation

2 GENOTOXICITY Oasis

3 Micronucleus ISSMIC NEW

4 Carcinogenicity&mutagenicity ISSCAN

5 HESS Repeated dose toxicity

Import/export new features

22.02.2012The OECD QSAR Toolbox for Grouping Chemicals into Categories 8

• Support of IUCLID 5.3 (import/export via i5z and web services)

• Added IUCLID Web Services logging for easier problem identification

• Renamed "Save as" to "Export" in the Profiling editor

• Changed horizontal export. It separates value and unit into different

columns

• Changed vertical export to separate value from unit. Unit is now in the

"Unit" field of the metadata header.

• Changed export form datamatrix popup - it now selects all sub-nodes.

Import/export new features

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• Fixed repainting of columns in vertical import

• Added Duration field for some IUCLID mappings

• Added "Save to file…" feature to import report form for IUCLID import as

well as generic import

• Added check for LIST-CLOSED fields during IUCLID5 export

Other new features

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• EPIWin v4.10 instead v4.00 is included• All databases are pre-calculated with ChemAxon module for pKa• Optimized caching of profiling (faster profiling)• Faster gather data on server version.• Input by chemical list - if some of the identifiers (CAS or SMILES) is missing the

system asks the user to search in the database by the other• Profile statistic: now user can group by category• Gap Filling module registers any kind of data points removals not described by the

prediction domain• TPRF introduces a new item in section 4.2. "Unambiguous algorithm (OECD

Principle 2)", which reports the above data points removals• The domain of any newly created model could be saved as a profiler category• Added points count to "Possible data inconsistency" form• Changed data gather prompt behavior. It now only asks once• Changed the Add/Remove of prediction to be accurately reflected by the statistics• Added caption to repeating values check form which shows the number of

chemicals, groups and data points.

Other new features

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• Added message after data gather with total data points and chemicals number.• Added scaling for 2D depiction• Disabled is starting of Toolbox two times. Second instance can make wrong

ECOSAR profiling• Sub-categorization window – display count of remaining chemicals• Copy information from cells of data matrix• Library with known units is expanded with over 200 new units and their

conversion formulas

Bug fixes

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• HESS database about count of imported data was wrong• After import  of new database show about was very slow ~1minute• Tab order in IUCLID5 Web Services login page• Bug which caused the 2D not to be cleared when clearing the Search

clause• Clearing the profiles list• Distorted images by PDF export in reports section are fixed• “Go forward” and “Go last” functionality in Gap Filling are fixed• A bug in QSAR import functionality is fixed• A missing part of the TPRF report (between points 4.2 & 4.4) is restored• Fixed bug where the "Data points" form would not display original data (in

case some scale transformation had been applied)• Removed "Multiple dimensions" prompt for QSARs with defined scale and

no data

Bug fixes

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• Fixed repeating values check where some data was not distinguished based on dynamic tree settings.

• (Q)SAR ranking function is fixed• Grouping by (UNDEFINED) categories is fixed• Strict category grouping when only part of targets categories are selected

is fixed