ORCHESTRA

There is a debate on the use of QSAR in particular, and in silico models in general. The acceptability of these tools depends on the user and the purpose.  Within that debate, the major criticisms are that ‘In silico models are not reliable’, that ‘toxicity is too complex to be modelled’ and that ‘only the real experiment on the animal will provide the real result’.

All in silico models should give a proof of their performance. In the past, the classical models were developed using all data, which were used to build up a model without any validation of the model. The points were fitted in a linear regression, and no demonstration was given if this regression was applicable to other chemicals (Kaiser, K. L. E. at all, 1999).

The interest on the use of in silico models for regulatory purposes contributed to the discussion on the validation of the in silico models (for more info refer to the regulatory context area of this website). A clear definition of the possible use of the model should be given, and pitfalls clearly indicated, for all in silico methods, such as QSAR, read-across and docking studies. Examples in this direction are the tools developed within CAESAR, which guide the user, indicating results on similar compounds, and errors.

Even if toxicity is complex, some phenomena are simplier and rules have been identified. For instance, in case of aquatic toxicity most of the chemicals can be explained with quite simple relationships (for more info refer to the DEMETRA project). Genotoxicity has been modeled in large extent on the basis of some toxic fragments or related QSAR models (more info at CAESAR project). Improvement seems possible, on the basis of more data (and there are huge initiatives in this direction, such as ToxCast), better models, and integration of models.

Even in vivo models cannot provide all answers. A wise integration of models, including in silico models, can only improve our knowledge. In silico models take advantage of computers to better examine the data and information available. Disregard this would mean not to use all pieces of information we have.

Watch the ORCHESTRA video documentary based on interviews with regulators, industry and QSAR developers.

Click here to view an interview with Professor Wim de Coen, Head of Evaluation 1 at the European Chemicals Agency (ECHA)