QSPR models as tools for predicting physico-chemical properties for REACH
Résumé
The new EU regulation REACH requires the evaluation of the physico-chemical properties of a large number of existing substances (143 000 pre-registered substances in 2008) in order to allow their use before 2018. Due to the number of substances and properties, the timing, the economic costs, the feasibility at the R&D level and the risks for the manipulator, in particular for the characterization of the dangerous physico-chemical properties (explosibility, flammability), the complete gathering of data solely based on experimental measurements is not realistic. Thus, the use of alternative predictive methods was recommended in the framework of REACH for the evaluation of the properties of substances. In this context, the French PREDIMOL (molecular modeling prediction of physico-chemical properties of products) project [1] funded by ANR (National Research Agency) has been conducted by INERIS associated with several public and private partners during three years. Its objective was to demonstrate that molecular modeling, notably through QSPR (Quantitative Structure- Property Relationships), is a credible alternative approach to experimental characterization to access, in a reliable and fast manner, to the whole range of physico-chemical properties of substances required by EU-REACH's regulation (annexes VII and IX) and for the industry in property-screening processes. The present contribution focuses on the use of QSPR models to predict the hazardous physico-chemical properties of amines and organic peroxides. At first, an inventory of existing experimental data from literature has been established. Additional experiments were performed to develop the largest database on thermal stability of organic peroxides after the Datatop (compiled from regulatory tests by TNO). Then, existing models applicable to these compounds were identified, stressing onto performances and limits of each model, and tested. Finally, new QSPR models were developed. In particular, this work led to the first reliable models for the thermal stability of organic peroxides validated according to the OECD principle for their use into regulatory context [2]. The last objective of the PREDIMOL project was to promote the use and validation of models in regulatory context. INERIS proposed the integration of its models into the EChA/OECD QSAR Toolbox, an open access prediction platform to help industrials and regulators for the gathering of properties in the context of REACH. The first INERIS model (for the impact sensitivity of nitro compounds) was implemented in the last version of the Toolbox [3] representing up to now the only included model for hazardous physico-chemical properties.