The international co-operation among the OECD member countries on (Q)SARs started in 1990 with a review of the availability and the predictive power of QSAR models, and a number of reports were produced.

Following a workshop organised by CEFIC and ICCA on "Regulatory Use of (Q)SARs for Human Health and Environmental Endpoints" in Setubal, Portugal, the OECD member countries agreed to initiate an activity to develop an internationally accepted set of criteria, as well as procedures for the evaluation of existing and promising (Q)SAR models. The OECD principles for the validation of (Q)SAR models were agreed upon in 2004, and a guidance document was published in 2007.

In November 2004, the OECD member countries recognised that the focus of the work should shift to the regulatory use and application of (Q)SARs. The major work in this field was the development of the OECD (Q)SAR Toolbox firstly released in March 2008, and updated in December 2008. Version 2.0 was released in October 2010.

QSAR Toolbox version 3.0 was released in October 2012.