Theoretical prediction of physico-chemical properties of chemicals for regulatory purposes
Résumé
The use of alternative methods to experimental testing was encouraged by REACH for the gathering of (eco)-toxicological properties but also for physico-chemical properties in order to allow the use of substances in EU market before 2018. Indeed, taking into account the number of substances and properties, the timing, the economic costs, the feasibility at the R&D level and the risks for the manipulator, the measurement of all the data was not realistic. If QSPR methods were particularly targeted by REACH, molecular scale modeling, in general, can play a critical role. In this context, a detailed review of the literature of the molecular modeling approaches (group-contributions, QSPR, equations of states, COSMO-RS/SAC and molecular simulations) available for the theoretical prediction of physico-chemical properties required by the REACH regulation (annexes VII and IX) was performed within the French PREDIMOL project (http://www.ineris.fr/predimol/), apart from 3 properties that are not directly dependent on the molecular scale properties of the substance. The objective was to stress onto required input information, performances and limits of each approach for all these properties and to give practical information to one user. From this work, a review for Chemical Reviews was written by the partners of this project and revealed that these predictive methods are pertinent alternative/complementary approaches to provide quick and reliable predictions of the physico-chemical properties of substances based only on the knowledge of their molecular structures. Authors indicated also that the selection of a method should be guided by the property to predict and the targeted compound.