Ineris http://hdl.handle.net/10967/207 2026-04-16T08:40:38Z 2026-04-16T08:40:38Z http://hdl.handle.net/10967/231 2024-01-19T14:54:29Z 2020-04-30T11:08:34Z

Quantitative structure–property relationships represent a powerful method alternative to experiments to access the estimation of physico-chemical properties of chemical substances. Such predictions are useful for screening purpose at R&D level. Moreover, this approach is encouraged by the REACH regulation for the collection of data when used cleanly and transparently. The impact sensitivities of 60 nitramine compounds were investigated in a QSPR study following the five principles of validation defined by OECD for the use of models in a regulatory framework. Only constitutional descriptors were employed to achieve QSPR models that could be used without any time consuming preliminary structure calculations at quantum chemical level. To validate models, the original data set was partitioned into a training and validation set. A series of 17 partitions, based on two ratios (40/20 and 45/15) and two division methods (property ranking and random division), were used to achieve this goal. From these partitions, four models exhibiting good predictive power using only constitutional descriptors were highlighted. These models are easier to apply than our previous quantum chemical based model, since they do not need any preliminary calculations.

2020-04-30T11:08:34Z http://hdl.handle.net/10967/230 2024-01-19T14:54:29Z 2020-04-28T11:09:57Z

Quantitative structure‐property relationships represent alternative method to experiments to access the estimation of physico‐chemical properties of chemicals for screening purpose at R&D level but also to gather missing data in regulatory context. In particular, such predictions were encouraged by the REACH regulation for the collection of data, provided that they are developed respecting the rigorous principles of validation proposed by OECD. In this context, a series of organic peroxides, unstable chemicals which can easily decompose and may lead to explosion, were investigated to develop simple QSPR models that can be used in a regulatory framework. Only constitutional and topological descriptors were employed to achieve QSPR models predicting the heat of decomposition, which could be used without any time consuming preliminary structure calculations at quantum chemical level. To validate the models, the original experimental dataset was divided into a training and a validation set according to two methods of partitioning, one based on the property value and the other based on the structure of the molecules by the mean of PCA. Four QSPR models were developed upon the type of descriptors and the methods of partitioning. The 2 models issuing from the PCA based method were highlighted as they presented good predictive power and they are easier to apply than our previous quantum chemical based model, since they do not need any preliminary calculations.

2020-04-28T11:09:57Z http://hdl.handle.net/10967/209 2024-01-19T14:54:29Z 2019-09-27T13:14:29Z

The 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 physico-chemical, 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 nitroaliphatic compounds were correlated with their impact sensitivities (h50%) using such predictive models. More than 400 molecular 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.

2019-09-27T13:14:29Z