DEMETRA project

European Projects on QSAR and Regulations 8.6.1 The DEMETRA Project... 

The DEMETRA project [20, 26] represents the first important case of a European project to develop QSAR models for regulatory purposes. DEMETRA developed five free models to determine the ecotoxicity of pesticides using endpoints that include trout, daphnia, bees, and quails (oral and dietary exposure). Since the target was to develop models for the user, these five endpoints were decided by them, not by the developers. 

We notice that in practically all cases, a QSAR model was developed having only considered the data availability, without the other assessment evaluation carried out for the DEMETRA project. 

Regulators and stakeholders within DEMETRA project defined that an accepted uncertainty of the toxicity experimental data was a factor of 4. If the data uncertainty for the same chemical was higher, the chemical was not used for the model in the training set. Here, we notice that QSAR studies do not involve looking at the uncertainty of the property/toxicity value, thereby highlighting the difference between typical and regulatory models. 

The full details of the DEMETRA project are available, with full description and explanation [26] and the models and structures are also available [20]. 

E. Benfenati, The specificity of the QSAR models for regulatory purposes the example of the DEMETRA project. SAR QSAR Environ. Res. 18, 209-220 (2007)... 

Another aspect is that multiple QSAR models can exist, and indeed this is likely. The consequences of such a complex picture, with many endpoints and models based on different approaches, are that it is not realistic to have a single approach, but the models have to be modulated considering these issues. Different approaches can be used for the same target and they improve the reliability of the prediction. In some cases, they have been combined into a unified system to improve overall results. This is the case of the models for regulatory purposes developed within the project DEMETRA (see below). 

The approach of CAESAR is quite similar to that of DEMETRA. So far good results have been obtained for the bioconcentration factor (BCF) in fish, superior to those of other models. Models have been tested with an external validation set. The model gives as prediction the BCF as continuous value, but it has been optimized to reduce false negatives. In the specific case of the REACH legislation, which is the target of the project, bioaccumulative chemicals are defined if the BCF value is above 3.3 in logarithmic unit. This shows another example of the specificity of the models, because different threshold may apply in other countries. 

The EC funded project CHEMOMENTUM will also implement QSAR models for pesticides and industrial chemicals, taken from the DEMETRA and CAESAR projects, and presented in a more user-friendly form [29]. 

CHEMOMENTUM is working with the XML standard. XML has been identified as the preferable standard within the information technology community for QSAR (see for instance the US EPA DSSTox database and the EC projects CHEMOMENTUM, DEMETRA, and OpenMolGRID). 

Very recently the EC funded project DEMETRA (http //www.demetra-tox. net) developed a series of QSAR models for the prediction of toxicity of pesticides toward five endpoints trout, daphnia, quail (oral and dietary exposure), and bee [80]. This project introduced a number of innovative issues, compared to previous QSAR models. The target of the project was to develop models for pesticides to be used for regulatory purposes in accord with European legislation. A questionnaire was distributed to a great many end-user to identify their needs. The endpoints to be modeled were chosen from among those defined in writing by the end-user, and not by the modeler, in order to make the models as useful as possible. This attention to the needs of the end-users is unique in the use of QSAR for ecotoxicity prediction. Other novel... 

We acknowledge the EC funded projects DEMETRA (QLRT-2001-00691), HAIR (SSPE-CT-2003-501997), EUFRAM (QLRT-2001-01346) and CHEMOMENTUM (1ST-2005-033437). 

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