QSAR model reproducibility and applicability: a case study of rate constants of hydroxyl radical reaction models applied to polybrominated diphenyl ethers and (benzo-)triazoles

Abstract

The crucial importance of the three central OECD principles for quantitative structure-activity relationship (QSAR) model validation is highlighted in a case study of tropospheric degradation of volatile organic compounds (VOCs) by OH, applied to two CADASTER chemical classes (PBDEs and (benzo-)triazoles). The application of any QSAR model to chemicals without experimental data largely depends on model reproducibility by the user. The reproducibility of an unambiguous algorithm (OECD Principle 2) is guaranteed by redeveloping MLR models based on both updated version of DRAGON software for molecular descriptors calculation and some freely available online descriptors. The Genetic Algorithm has confirmed its ability to always select the most informative descriptors independently on the input pool of variables. The ability of the GA-selected descriptors to model chemicals not used in model development is verified by three different splittings (random by response, K-ANN and K-means clustering), thus ensuring the external predictivity of the new models, independently of the training/prediction set composition (OECD Principle 5). The relevance of checking the structural applicability domain becomes very evident on comparing the predictions for CADASTER chemicals, using the new models proposed herein, with those obtained by EPI Suite.