7 reasons to use in-silico methods

1. Cost and feasibility

The REACH legislation requires industry to evaluate the toxicity not just of new chemicals, but also of the tens of thousands of existing chemical substances that are currently in use but have never been subject to regulatory testing.  Many argue that to achieve this by traditional in vivo testing would take decades, cost billions and consume many millions of vertebrates.  In addition to the time and costs for industry, there is a lack of laboratories in Europe capable of performing in vivo tests for such large numbers of substances.

In this context, in silico models are potentially vital because they use computer technology to connect, use and extend existing experimental data.  When experimental data sets are already available from in vivo or in vitro tests, then in silico methods can be used to assess thousands of chemicals in a day.

In previous regulation there was no need to use in silico methods.  It is only with new legislation that the need becomes apparent …  there is no choice but to use in silico technologies, just to get the work done.

Bob Diderich, OECD, interviewed for the ORCHESTRA documentary
‘QSARs in REACH? Uses, issues and priorities.’

In silico methods therefore offer an important way for European industry to meet the REACH demands, and to do so at a cost that will not destroy SMEs and/or move chemical industries and testing to other parts of the world.  In silico methods can be used on an office computer, so even with the costs of expert advice, they are cheaper than in vivo testing by orders of magnitude.

2. Innovation

REACH explicitly encourages innovation in toxicity evaluation.  The development of alternative methods is one of the purposes of REACH.  The legislation sets out conditions specifically for the use of QSAR models, and the European Chemicals Agency (ECHA) offers detailed guidance on their use.  Even the introductory ‘Guidance in a nutshell’ on substance registration advises industry to ‘collect QSAR estimated results for the substance if suitable models are available’ as an initial step.

3. The focus on ‘weight of evidence’

REACH demands that industry review all the available evidence, which in many cases will include evidence produced by QSAR models.  The demand to review all the evidence is part of a regulatory shift away from relying on a single in vivo study, towards reviewing the ‘weight of evidence’ developed from a range of complementary sources.  QSAR models are recommended by ECHA as a valuable source of evidence, and supporting evidence, in a ‘weight of evidence’ approach.

4. Animal testing as ‘a last resort’

REACH demands the use of existing data where possible, and states that further animal testing can only be used ‘as a last resort’:

'The challenge is to have scientifically sound information on the potential hazards of substances whilst at the same time minimising unnecessary animal testing.  One of the fundamental aims of REACH is to promote alternative methods for assessing hazards of substances and to see animal testing as a last resort.  All parties involved should take this very seriously…'

Geert Dancet, Executive Director of ECHA, Press Release: August 2009
http://echa.europa.eu/doc/press/pr_09_11_animal_testing_20090828.pdf

Reducing or avoiding the use of many additional millions of vertebrates to test existing chemicals is not just a policy priority, it also matches the desire of many industry shareholders, managers and consumers, and is a major concern for citizens and NGOs.

5. Prioritisation

In-silico methods offer a valuable tool for prioritising substances according to their toxicity, so that costly experimental tests can be focussed on those substances with higher probability of toxicity and higher risk.  Well-informed prioritisation can reduce economic costs, time delays and the use of vertebrates.

6. Pro-active decision-making

The predictive ability of in silico methods enables a pro-active approach to toxicity within product development.  Toxicity evaluation can be brought ‘upstream’ in the product development and decision making processes, so that chemicals are selected, and products are developed, to be less toxic or non-toxic.  In this way future toxicity, and therefore future costs and future impacts on health and environment, can be reduced or avoided.

7.     The future of toxicology

REACH creates a potential turning point in regulatory toxicology.  Looking ahead, and beyond Europe, the Tox21 and ToxCast initiatives in the USA are expected to reshape the toxicological procedures for evaluation of chemicals.  By providing up-to-date toxicity data for thousands of chemicals, these major projects will put in silico models in a central role.  Experience and understanding of in silico models will be essential for analysing and making full use of those data in future toxicity evaluations.

To cite or quote from this page, please use the reference:

ORCHESTRA (2011) Why use QSAR models and other in silico methods?  EC-FP7 funded project No. 226521

Further information: 

1)  The documentary ‘QSARs in REACH? Uses, issues and priorities’, offers perspectives from regulators (section 1), an introduction to the priorities when selecting and using a QSAR model (section 2), and industry representatives talking from experience (section 3). 

2) The video interview with Professor Wim de Coen, Head of Evaluation 1 at ECHA, provides further insight into ECHA’s thinking on in silico methods / QSAR models and their current uses. 

3) The following open access article offers further detail:
Benfenati, E., Gonella Diaza, R., Cassano, A., Pardoe, S., Gini, G., Mays, C., Knauf, R. and Benighaus, L. (2011) The acceptance of in silico models for REACH: Requirements, barriers, and perspectives.  Chemistry Central Journal 2011, 5:58  http://journal.chemistrycentral.com/content/5/1/58

4) Further detail on the reasons for using QSAR models is also contained in the many ECHA guides, including:

• ECHA (2009) Guidance in a nutshell: Registration data and dossier handling http://guidance.echa.europa.eu/guidance2_en.htm   ECHA-09-B-13-EN
• ECHA (2010)  Practical Guide 10.  How to avoid unnecessary testing on animals. http://echa.europa.eu/doc/publications/practical_guides/pg_10_avoid_anim...
• ECHA (2009) Practical guide 5: How to report (Q)SAR.  http://echa.europa.eu/doc/publications/practical_guides/pg_report_qsars.pdf
• ECHA (2008) Guidance on information requirements and chemical safety assessment: Chapter R.6: QSARs and grouping of chemicals. 

5) The VEGA platform offers an accessible platform which is developed specifically to provide what REACH requires.  www.insilico.eu