Spreading the word about in silico toxicology
The EU REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) regulation requires industry to evaluate the toxicity of new chemicals, and of tens of thousands of existing chemical substances that are in use but have never been subject to regulatory testing. Many argue that to achieve this by traditional testing would take decades, cost billions and consume many millions of vertebrates. REACH therefore encourages innovation, requires the use of existing data where possible, and states that further animal testing can be used only ‘as a last resort’. Scientists in Milan therefore initiated the EU-funded ORCHESTRA (Organising dissemination on results of projects on chemical evaluation, spreading techniques for risk assessment) project. With other partners, they set out to develop a wider understanding of the latest computer-based (in silico) ‘QSAR’ methods for evaluating toxicity, and to share insights across sectors. Structure-activity relationship (SAR) models correlate structural features of a molecule with its toxicity effects (end points). While classical SAR models use evidence of toxicity and current understanding of the mechanisms of toxic action, Quantitative SAR (QSAR) models radically change this by utilising the power of computers to investigate and model SAR relationships mathematically. QSAR models can use all the available experimental data on toxicity for a range of related chemicals, to identify structural properties of the molecules that correlate statistically with particular toxicity end points. They can make use of potentially hundreds of existing experimental results to ensure reliability, to identify new toxicity correlations beyond those currently understood, and to evaluate potentially thousands of chemicals in a day. As the EU’s European Chemicals Agency (ECHA) advocate, when existing data is sufficient, QSAR models can complement and reduce, as well as replace, further costly animal testing. ORCHESTRA created a four-part video documentary titled 'QSAR in REACH: Uses, issues and priorities' from interviews with regulators, industry representatives and QSAR experts. Training materials for a 15-session course were developed for graduate and postdoctoral students and made available on the ORCHESTRA website. The project organised an international workshop to spur interaction among industry, regulators and software developers regarding the regulatory use of QSAR methods. ORCHESTRA representatives also participated in several international toxicology conferences, and put a video installation, computer terminals and expert support in a booth at the centre of the SETAC 2011 Europe conference. The project produced an e-book, 'Theory, guidance and applications in QSAR and REACH', as well as brochures, newsletters, videos, reports, articles and online information, to generate understanding and inspire change across sectors. These are available on the website and elsewhere. ORCHESTRA is improving toxicology assessment in line with EU policy, by providing stakeholders across sectors with an accessible understanding of QSAR models as alternative methods, and of how they can be used.
Keywords
Toxicology, alternative methods, QSAR, chemicals, toxicity assessments, chemical evaluation, structure-activity relationships, computer model, REACH
