QSARs have been used for decades in the development of pharmaceuticals, where a drug is to be developed to achieve a particular biological action.  Our interest here is in the reverse use, where the chemical is known, and the biological action is to be predicted.  That too has been the focus of research for decades.  But here we are concerned specifically with their use for evaluating toxicity within the regulatory framework of REACH, and it is early days.  

In practice, the use of in silico methods by European industry within REACH is still limited.  There are  three key practical issues that can delay their use.  They are highly inter-connected.

(i) Progress in developing models for regulatory use:  The limitations for model development are primarily the lack of good available experimental data as the basis for developing models.  The results of the many thousands of past animal experiments carried out or commissioned by industry are held as confidential by industry.   (The regulatory demand for the transparency of QSAR models inevitably requires that they not only reveal the experimental data used to develop the model, but also make available for independent review the details of how the experimental results were achieved.)  In his video interview (see documentary, part 4) Professor John Dearden made a plea to industry to release that data.  

A positive development is that it is now clearer to QSAR developers than ever before, exactly what is expected of QSAR models for regulatory use.  The regulatory framework of REACH, the OECD principles and the ECHA guidelines effectively work together to increase the demands on models in terms of rigour, reliability and transparency.    

(ii) Uptake by industry and consultants: uptake requires awareness of the models available, confidence in their reliability and confidence in regulatory acceptance if they are used.  (See the FAQ: ‘Do in silico methods require expertise, or can anyone use them?’)  The use of in silico methods for REACH also involves a simultaneous shift from simply using in vivo methods as an accepted form of evidence, to using different and complementary sources of evidence.  

(iii) Acceptance in practice by regulators (ECHA and the national competent authorities):  The ultimate responsibility of regulators is to protect human health and the environment, so there is some caution in accepting the use of alternative methods.  The experience of European regulators in using QSARs is also still limited.  

The regulation has made the shift to animal testing being ‘only as a last resort’, but process requires confidence, shared expertise and communication between these three major stakeholders.  It may be encouraged by wider interest among industry shareholders, publics, and policy makers, in realisation that there are alternatives to animal testing.