The OECD QSAR Toolbox is a software designed to support hazard assessment of chemicals as well as to increase mechanistic and other knowledge on chemical substances in a cost-efficient way. As a freely available computational tool, it promotes the use of assessment methods alternative to animals and minimizes unnecessary animal testing without reducing the safety of human health and environment. It is intended to be used by governments, chemical industry and other stakeholders.
At a glance, computational tools reduce the use of animals in laboratory tests, reduce the cost for testing and increase the number of chemicals which are assessed for their effects upon human health and the environment. The toxicity of substances can be predicted even before they are produced, facilitating sustainable product development and green chemistry.
The functionalities of the OECD QSAR Toolbox serve users with sufficient understanding of (eco)toxicology as a decision support system for hazard assessment:
- Prevent duplication of animal tests. When existing high quality data are found, there is no need to duplicate the test.
- Intelligent testing strategies. By forming categories and identifying data gaps, informed testing strategies can be designed to optimize costs and number of animals required.
- Predict toxicity using a category approach. The Toolbox results can be used for data-gap filling and as supporting evidence for read-across cases.
- Sustainable development and green chemistry. The toxicity of substances can be predicted even before they are produced, facilitating sustainable product development and green chemistry.
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.
Progressive maintenance of QSAR Toolbox
Current phase of the Toolbox development starts 2019.
The topics of this phase are related to three main areas:
- 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.
This phase will end in May 2020.
The OECD QSAR Toolbox is co-owned by OECD and ECHA. ECHA, OECD and LMC (Toolbox developer) form the QSAR Toolbox Coordination Group. ECHA has the mandate under REACH to promote the use of alternative methods while ensuring the implementation of the regulation. OECD convenes the QSAR Toolbox Management Group which consists of OECD member and partner countries and stakeholders under the Working Party on Hazard Assessment in order to discuss and approve new developments of the QSAR Toolbox.
The Laboratory of Mathematical Chemistry (LMC) is the primary contractor of the OECD QSAR Toolbox development. LMC was established in 1984 in Burgas, Bulgaria at “Prof. Dr. As. Zlatarov” University. The major activities of LMC are related to SAR and QSAR modelling of ecological (persistence, bioaccumulation, mode of action, acute toxicity, phototoxicity, etc.) and human health endpoints (skin sensitization, genetic toxicity, receptor mediated effects), database building and in silico simulation of metabolism and catabolism. LMC is a leading developer of metabolic simulators for tissue and microbial biotransformations of chemicals for predicting endpoints such as biodegradation, bioaccumulation, genotoxicity, skin sensitization, receptor mediated endpoints, etc.
LMC has a research staff of about 40 scientists experienced in chemistry, physics, mathematics and programming.