Areas of applicability
QSAR models have been developed for many applications:
- Physico-chemical properties, such as boiling point, water solubility, partition coefficients. The U.S. EPA Estimation Program Interface (EPI) suite comprise models for these endpoints (http://www.epa.gov/oppt/exposure/pubs/episuite.htm).
- Environmental properties, such as bioconcentration factor (included in the CAESAR software), degradation, soil adsorption, photodegradation.
- Ecotoxicological properties, such as fish, daphnia, bird, bee toxicity. Models for these endpoints have been developed by the DEMETRA project.
- Toxicity, such as carcinogenicity, mutagenicity, developmental toxicity, skin sensitization. All these endpoints have been modelled by the EC funded project CAESAR and implemented in the on line freely available CAESAR software.
Typically, the performance of the QSAR models are better for physico-chemical properties, and decrease with the increase complexity of the studied system. For certain human endpoints, such as carcinogenicity and developmental toxicity, the general position is that in silico models should be used as unique tool, but as support for the evaluation based on several methods.
For aquatic toxicity, most of the models address acute toxicity, mainly in fish. Results are good for chemicals which do not carry residues which increase their toxicity, which applies to about 30% of the cases. Specific models for more toxic compounds should not be used in these cases.
Models for mutagenicity (mainly Ames test) generally give good results (accuracy about 80%, which is close to the test reproducibility).
Models for bioconcentration factors (BCF) give good results (R2 about 80%; error about 0.5 log unit). Care should be taken if the predicted value is close to the threshold, while if the predicted value is well above or below the BCF threshold, the prediction is much more reliable.
Models for carcinogenicity give a quite large error. About one out three chemicals is wrongly predicted. Better results can be obtained if the applicability domain of the model is evaluated. At least three models for carcinogenicity should be used, because the results vary. In case of agreement, the prediction is more reliable.
Several platforms of QSAR models exist. The ANTARES project lists hundreds of QSAR models, tens of them are freely available.
Some well known platforms are:
VEGA: The ORCHESTRA project, with ANTARES, has developed the VEGA platform, which incorporates CAESAR and T.E.S.T. models into a single framework. An advantage of the VEGA platform is the facilitated and supported user-access: supporting information, tutorials and videos are all available on the web site. It has been developed from the point of view of the user, and of the REACH requirements. Each model produces not only a predicted value, but also many pages of explanation and assessment of its reliability.
A concise and accessible explanation of in silico methods and the issues around them, for people who want to know about them, and/or want to understand what the ORCHESTRA project is about. Download the leaflet
- About Orchestra
- About In-silico
- Why use in-silico?
- News & Activities
- Get Involved