June 2005

Member state countries approved the idea for developing a centralized software system for predicting toxicity of chemicals by applying the category approach.

Phase I of OECD QSAR Toolbox development

The concept of the first phase relied on the concept of similarity between chemicals and was inspired by Gilman Veith.

The objective of Phase I was to develop a working prototype integrating in a single software platform, knowledge and data which to be used for grouping of chemicals and data gap filling. The initial knowledge and data was donated by the member state countries.

Version 1.0 of the Toolbox consisted of 21 profilers and 18 databases. The basic functionalities which were implemented into first version of Toolbox were:

• Profiling—the process of retrieving information about the functional groups identified in the molecules by applying the knowledge implemented in the profilers
• Collecting experimental data for a single chemical or a list of chemicals
• Defining a category—the process of collecting analogs by applying specific profilers
• Data gap filling—the process of making prediction by using read across, trend analysis or by applying an external QSAR model.

Phase I was completed with the release of Version 1.0 of the Toolbox, in October of 2008.

It was approved by the member state countries as a tool for applying the category approach for searching of analogues.

Phase II of OECD QSAR Toolbox development

The second phase of the Toolbox development started in collaboration with the European Chemicals Agency. The aims of this phase were to improve the information technology and to streamline the workflow process of the system. The work addressed about 50 specific topics which fell into one of the focus areas:

• Information technology
• Interface improvements and additional functionalities
• Database compilation
• QSAR library and expert system compilation

Interface of the program was changed and additional functionalities were developed related to chemical identification and query tools. Handling of metabolism in the category formation and prediction of mixtures properties were also introduced. New simulators for autoxidation, acidic, basic and neutral hydrolysis were included. Some of the profilers and metabolic simulators were updated. Additionally, existing databases were expanded and new databases added.

The continuous improvement in the Toolbox during Phase 2 led to numerous revisions released in the period 2010-2013:

• Versions 2.0 – 2.3 of the Toolbox were released in 2010-2012,
• Versions 3.0 – 3.3 were released between 2013-2014
• Final Version 3.4 of Toolbox in Phase II was released in 2016

Phase III of OECD QSAR development

The main areas of development in Phase 3 are usability improvements, scientific developments, additional functionalities and improvement of information technology. As a starting step in this phase, Toolbox was completely rewritten by using Microsoft’s .NET framework. The database engine was also changed from Firebird to PostgreSQL. Other key improvements and developed functionalities include:

• Using of Daylight SMILES to represent chemical connectivity
• Using of SMARTS language to code structural fragments (sub-structure searching)
• Improved unit of measurements subsystem
• Expanded species taxonomy
• Extended functionality for grouping with metabolism
• Developing of Automated and standardized workflows
• Defining of the target endpoint and showing relevant profilers and databases.
• Evaluation of alert performance allowing estimation of the predictive capability of a given alert with respect to a defined endpoint.
• Accessibility to the document tree at any time of the workflow process
• Possibilities to filter, sort and color by different attributes the profilers and databases.
• Implementation of Category consistency assessment
• Redesign of the report to account for the category elements (related to Category consistency) and addition of RAAF templates.
• Exposing Toolbox functionalities as web services

Several versions of Toolbox were released in 2014-2018:

• Version 4.0 was released in March 2017
• Version 4.1 was released in August 2017
• Version 4.2 was released in January 2018 and further updated to versions 4.2.1 and 4.2.2 in August and October 2018.

Phase IV of OECD QSAR development

The main areas of development in the current IV phase are focused on the harmonization of the data usage, simplification of the workflow process, utilization of new approach methodologies (NAM) data and maintenance of the website, online repository and user support.

The first tasks of this phase, included in the period 2019-2020 are related to:

• Simplification of the workflow – introducing task specific simplified interface
• Connectivity – related to on-line repository for external modules (QSAR, Profilers, etc.)
• Development of new features – editor of workflows, relevancy of endpoints, etc.

The phase is further continued with the following main tasks during the years:

• 2020-2021 – Expansion of the Toolbox (Web)API and documentation and further development of the Web Client
• 2021-2022 – Update of the IUCLID plug-in, reports and QSARs, and other improvements
• 2022-2023 – Further work on the data and web functionalities of the QSAR Toolbox, and other improvements
• 2023 – Extension of data in the QSAR Toolbox, update of modules and reports, and other improvements
• 2023-2024 – Extension of availability of data for observed metabolism in QSAR Toolbox and progressive maintenance of the Toolbox software and related products

Several versions were released in 2019-2023:

• Version 4.3 was released in February 2019
• Version 4.4 was released in February 2020 and further updated to version 4.4.1 in April 2020
• Version 4.5 was released in September 2021 and further updated to version 4.5SP1 in March 2022
• Version 4.6 was released in May 2023