Decomposition mechanisms of trinitroalkyl compounds : a theoretical study from aliphatic to aromatic nitro compounds

International audienceThe chemical mechanisms involved in the decomposition of trinitroethyl compounds were studied for both aliphatic and aromatic derivatives using density functional theory calculations. At first, in the case of 1,1,1-trinitrobutane, used as a reference molecule, two primary channels were highlighted among the five investigated ones: the breaking of the C-N bond and the HONO elimination. Then, the influence of various structural parameters was studied for these two reactions by changing the length of the carbon chain, adding substituents or double bonds along the carbon chain. If some slight changes in activation energies were observed for most of these features, no modification of the competition between the two investigated reactions was highlighted and the breaking of the C-N bond remained the favoured mechanism. At last, the reactions involving the trinitroalkyl fragments were highlighted to be more competitive than reactions involving nitro groups linked to aromatic cycles in two aromatic systems (4-(1,1,1-trinitrobutyl)-nitrobenzene and 2-(1,1,1-trinitrobutyl)-nitrobenzene). This showed that aromatic nitro compounds with trinitroalkyl derivatives decompose from their alkyl part and may be considered more likely as aliphatic than as aromatic regarding the initiation of their decomposition process

Development of a new QSPR based tool to predict explosibility properties of chemical substances within the framework of REACH and GHS

International audienceThe new European régulation of Chemicals named REACH (for "Registration, Evaluation and Authorization of Chemicals") turned out in the practical registration phase in December 2008. It requires the new assessment of hazard properties for up to 140000 substances. In this context, the development of alternative prédictive methods for assessing hazardous properties of chemical substances is promoted in REACH and in the related new European classification System of substances CLP (Classification, Labelling and Packaging of chemical substances and mixtures

Prediction of physico-chemical properties for REACH based on QSPR models

International audienceQuantitative Structure Property Relationship models have been developed for the prediction of flash points of two families of organic compounds selected in the PREDIMOL French Project: amines and organic peroxides. If the model dedicated to amines respected all OECD validation principles with excellent performances in predictivity, the one dedicated to organic peroxides was not validated on an external validation set, due to the low number of available data, but already presented high performances in fitting and robustness. This work highlighted the need of gathering experimental data, as in progress in the PREDIMOL project, to achieve validated reliable models that could be used in a regulatory framework, like REACH. Such models are expected to be submitted to the European Joint Research Comity (JRC) and to existing tools (like the OECD ECHA QSAR Toolbox) to be available for use by industrials and regulatory instances

Development of a QSPR model for predicting thermal stabilities of nitroaromatic compounds taking into account their decomposition mechanisms

International audienceThe molecular structures of 77 nitroaromatic compounds have been correlated to their thermal stabilities by combining the quantitative structure-property relationship (QSPR) method with density functional theory (DFT). More than 300 descriptors (constitutional, topological, geometrical and quantum chemical) have been calculated, and multilinear regressions have been performed to find accurate quantitative relationships with experimental heats of decomposition (deltaH). In particular, this work demonstrates the importance of accounting for chemical mechanisms during the selection of an adequate experimental data set. A reliable QSPR model that presents a strong correlation with experimental data for both the training and the validation molecular sets (R 2 = 0.90 and 0.84, respectively) was developed for non-ortho-substituted nitroaromatic compounds. Moreover, its applicability domain was determined, and the model's predictivity reached 0.86 within this applicability domain. To our knowledge, this work has produced the first QSPR model, developed according to the OECD principles of regulatory acceptability, for predicting the thermal stabilities of energetic compounds

On the prediction of thermal stability of nitroaromatic compounds using quantum chemical calculations

International audienceThis work presents a new approach to predict thermal stability of nitroaromatic compounds based on quantum chemical calculations and on quantitative structure-property relationship (QSPR) methods. The data set consists of 22 nitroaromatic compounds of known decomposition enthalpy (taken as a macroscopic property related to explosibility) obtained from differential scanning calorimetry. Geometric, electronic and energetic descriptors have been selected and computed using density functional theory (DFT) calculation to describe the 22 molecules. First approach consisted in looking at their linear correlations with the experimental decomposition enthalpy. Molecular weight, electrophilicity index, electron affinity and oxygen balance appeared as the most correlated descriptors (respectively R2 = 0.76, 0.75, 0.71 and 0.64). Then multilinear regression was computed with these descriptors. The obtained model is a six-parameter equation containing descriptors all issued from quantum chemical calculations. The prediction is satisfactory with a correlation coefficient R2 of 0.91 and a predictivity coefficient R2(cv) of 0.84 using a cross validation method

Nanomaterials risk assessment in the process industries : evaluation and application of current control banding methods

International audienceNanotechnology is a rapidly growing field and industrial developments are more and more challenged by potential health and safety risks pertaining to manufactured nanomaterials. This matter is far from being solved due to the current lack of reliable data addressing occupational safety as well as environmental field. In this context, the Control Banding (CB) approach appears particularly interesting to assess ESH risks associated to nanomaterials. Our study focuses more specifically on four CB methods which have been analysed in order to highlight their a priori limits and evaluate their effectiveness for perform risk assessment in the industry. Our study concludes that too conservative frameworks, multiplicity of factors and complex algorithm are critical elements that can limit the effectiveness of the tools for risk assessment in the industry

On the development of QSPR models for regulatory frameworks : The heat of decomposition of nitroaromatics as a test case

International audienceMany regulatory frameworks, e.g. related to the Transport of Dangerous Goods, the Registration, Evaluation, Authorisation and restriction of chemicals (REACH) or the Classification, Labelling and Packaging of substances and mixtures (CLP), require the characterization of the hazards of chemicals, which could be complex. In particular, the REACH regulation involves an extensive quantity of works, to gather toxicological, eco-toxicological and physico-chemical properties for a large number of compounds. So, the full characterization by experimental way is time-consuming and cost-expensive. Alternative methods are therefore encouraged to complement experimental tests. The Quantitative Structure-Property Relationships (QSPR) approach is one of the recommended methods, provided that they are developed within the rigorous guidelines proposed by the Organization for Economic Co-operation and Development (OECD). In this context, a series of nitroaromatic compounds has been analyzed to achieve new QSPR models for the prediction of their heat of decomposition respecting the requirements for application in regulatory frameworks. Three multilinear models were obtained upon the set of descriptors considered for their development (constitutional, topological or both) that do not need any preliminary time expensive quantum chemical calculations. They were tested by internal and external validation tests. Good performances for the two ones including constitutional descriptors were obtained in particular in terms of predictive power in a well defined applicability domain (R2IN = 0.81-0.87). They are easier to apply than our previous quantum chemical based model, since they do not need any preliminary calculations

Développement de modèles QSPR pour la prédiction des propriétés d'explosibilité des composés nitroaromatiques

The aim of these works consisted in the development and evaluation of quantitative structure property models (QSPR) for the prediction of explosive properties of nitroaromatic compounds, to be used within a regulatory context, in particular the new European regulation called REACH. Different methodological approaches (multilinear regressions, PCA, PLS, decision trees) were used to develop models for the prediction of the heat of decomposition. The descriptors of the model are selected among an extended set of more than 300 (constitutional, topological, geometric and quantum chemical) descriptors. Applicability domains were defined and the predictive power was determined using a set of validation. Three other properties (decomposition temperature, electric spark and impact sensitivities) were also investigated, leading to similar or better performances than existing models. Then, subjacent mechanisms, analyzed from DFT calculations, brought to light specific decomposition paths for any nitroaromatic compounds. This study completed the QSPR analyses in terms of phenomenological interpretation. Finally, this study took into account all OECD principles for the validation of QSAR/QSPR models for regulatory uses (experimental endpoint, model structure, validation, applicability domain and interpretation of subjacent mechanisms). Moreover, two predictive models were developed for the heat of decomposition of nitroaromatic compounds.L'objectif de ces travaux était de développer et d'évaluer des modèles quantitatifs structure-propriété (QSPR) pour la prédiction des propriétés explosives des composés nitroaromatiques, en vue d'une utilisation dans un cadre règlementaire, en particulier celui du nouveau règlement européen REACH. Différentes approches méthodologiques (régressions multi-linéaires, PCA, PLS, arbres de décision) ont été utilisées pour mettre en place des modèles pour la prédiction de la chaleur de décomposition. Les descripteurs des modèles ont été sélectionnés dans un jeu étendu de plus de 300 descripteurs (constitutionnels, topologiques, géométriques et quantiques). Deux premiers modèles avec des domaines d'applicabilité définis et des pouvoirs prédictifs importants ont été obtenus. Des modèles pour trois autres propriétés explosives (la température de décomposition, les sensibilités à la décharge électrique et à l'impact) ont ensuite été développés, avec des performances similaires voire supérieures aux modèles existants. Enfin, l'analyse des mécanismes réactionnels sous-jacents, menée à l'aide de la DFT, a permis de mettre en évidence la présence de chemins de décomposition spécifiques au sein des composés nitroaromatiques et a ainsi complété l'approche QSPR en termes d'interprétation phénoménologique. Cette étude a donc pris en compte l'intégralité des principes mis en place par l'OCDE pour la validation des modèles QSAR/QSPR dans un usage règlementaire (cible expérimentale, structure du modèle, validation, domaine d'applicabilité et interprétation des mécanismes sous-jacents). Deux modèles prédictifs ont même été développés pour la chaleur de décomposition des composés nitroaromatiques

Development of validated QSPR models for impact sensitivity of nitroaliphatic compounds

International audienceThe European regulation of chemicals named REACH implies the assessment of a large number of substances based on their hazardous properties. However, the complete characterization of physicochemical, toxicological and eco-toxicological properties by experimental means is incompatible with the imposed calendar of REACH. Hence, there is a real need in evaluating the capabilities of alternative methods such as quantitative structure-property relationship (QSPR) models, notably for physico-chemical properties. In the present work, the molecular structures of 50 itroaliphatic compounds were correlated with their impact sensitivities (h50%) using such predictive models. More than 400 olecular descriptors (constitutional, topological, geometrical, quantum chemical) were calculated and linear and multi-linear regressions were performed to find accurate quantitative relationships with experimental impact sensitivities. Considering different sets of descriptors, four predictive models were obtained and two of them were selected for their predictive reliability. To our knowledge, these QSPR models for the impact sensitivity of nitroaliphatic compounds are the first ones being rigorously validated (both internally and externally) with defined applicability domains. They hence follow all OECD principles for regulatory acceptability of QSPRs, allowing possible application in REACH

Global and local quantitative structure-property relationship models to predict the impact sensitivity of nitro compounds

International audienceNew quantitative structure-property relationships were developed to predict accurately the impact sensitivity of nitro compounds from their molecular structures. Such predictive approaches represent good alternative to complete experimental testing in development process or for regulatory issues (e.g., within the European REACH regulation). To achieve highly predictive models, two approaches were used to explore the whole diversity of nitro compounds included in a dataset of 161 molecules. In the first step, local models, dedicated to nitramines, nitroaliphatics, and nitroaromatics, were proposed. After that, a global model was developed to be applicable for the whole range of the nitro compounds of the dataset. In both cases, large series of molecular descriptors were calculated from quantum chemically calculated molecular structures, and multilinear regressions were computed to correlate them with experimental impact sensitivities. Both the global and local models could predict nitramines and nitroaliphatics in high accuracy whereas nitroaromatics were more difficult to be predicted due to their complex decomposition mechanisms. The proposed models were validated in the perspective of potential regulatory use according to the OECD principles, including internal, external validation, and the definition of their applicability domain. So, they could then be used for prediction either separately or in a consensus approach