The new REACH (Registration, Evaluation, and Authorisation of Chemicals) legislation in the European Union means that the toxicological properties of some 30,000 chemicals will need to be assessed, resulting in additional information requirements. To address financial and animal welfare concerns, REACH explicitly expresses the need to use (Q)SARs to reduce the extent of experimental testing. Article 25(1) of REACH specifies that "in order to avoid animal testing, testing on vertebrate animals for the purposes of this Regulation shall be undertaken only as a last resort."
Since the publication of the REACH White paper in 2001, several activities were initiated to increase acceptance of (Q)SARs. The first of these included a workshop organized by the European Chemical Industry Council (CEFIC)/The International Council of Chemical Associations (ICCA) in Setubal, Portugal, in 2002 (Jaworska, et al., 2003). The workshop identified a number of principles for evaluating the validity of (Q)SARs. These were then evaluated by the OECD as part of the ad hoc group for (Q)SARs and are now referred to as the OECD Principles for the Validation of (Q)SARs. Anticipated applications where (Q)SAR models will play a greater role include providing information for use in priority setting procedures, guiding the experimental design of an experimental test or testing strategy, improving the evaluation of existing test data, providing mechanistic information, and filling data gaps needed for hazard and risk assessment, classification and labeling, or PBT or vPvB assessment (Worth, et al., 2007).
The European Chemicals Bureau (ECB) carries out a range of activities aimed at promoting the development, validation, and acceptance of (Q)SARs and the availability of reliable computer-based estimation methods. The ECB has evaluated (Q)SAR models with respect to the OECD principles, contributed extensively to the development of guidance for REACH as well as OECD guidance, and organized and led training courses for regulators. It has also commissioned a number of open source computer-based applications, which are made freely available via the ECB website. Recent tools include Toxtree (Ideaconsult, Ltd.), DART (Talete, Srl.) and Toxmatch (Ideaconsult, Ltd.). More details can be found here.
The OECD has been working for more than a decade to develop guidance on the validation of (Q)SAR models and on use of (Q)SARs in regulatory decision making; the details and links to relevant documents can be found on the OECD Quantitative Structure-Activity Relationships [(Q)SARs] Project page. In 2007, the OECD published the Guidance Document on the Validation of (Quantitative) Structure-Activity Relationship [(Q)SAR] Models and, in 2006, the Report on the Regulatory Uses and Applications in OECD Member Countries of (Q)SAR Models in the Assessment of New and Existing Chemicals. The OECD is also developing a (Q)SAR Application Toolbox so that models used by member countries for regulatory purposes are more accessible to others. A prototype will be made publicly available in March 2008.
The recently released OECD guidance document Guidance on Grouping of Chemicals provides for greater testing efficiency and animal welfare by the use of a category approach for related chemicals where "not every chemical needs to be tested for every endpoint." The guidance was developed in parallel with that being prepared for REACH. The dataset developed for a category must provide information sufficient for estimating the hazard of the untested chemicals and/or endpoints. Guidance was first provided for this approach in the US EPA’s and the OECD’s High Production Volume chemicals testing programs. The new OECD guidance provides the latest approaches and "is aimed at improving the visibility of this approach and at recommending its wider use." The document also explains the close association between categories and (Q)SARs and the use of both methods for filling data gaps.
The International QSAR Foundation fulfills its mission "to develop computerized tools as alternatives to animal testing" by supporting research for the development of (Q)SAR models for regulatory testing endpoints and by hosting annual workshops.
Additional information on other emerging research and policies relevant to (Q)SARs will be provided on AltTox.org in the future; please check back again.
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