In vivo toxicity of nitroaromatic compounds to rats: QSTR modelling and interspecies toxicity relationship with mouse

[Display omitted] •A highly robust QSTR model for the toxicity of NACs to rat was built.•Seven simple and easily interpretable 2D descriptors control the toxicity of NACs.•Two reliable iQTTR models between rat and mouse were developed.•QSTR and iQTTR models were firstly successfully applied to true external sets.•The proposed models can be used for toxicity data filling and risk assessment. Nitroaromatic compounds (NACs) in the environment can cause serious public health and environmental problems due to their potential toxicity. This study established quantitative structure-toxicity relationship (QSTR) models for the acute oral toxicity of NACs towards rats following the stringent OECD principles for QSTR modelling. All models were assessed by various internationally accepted validation metrics and the OECD criteria. The best QSTR model contains seven simple and interpretable 2D descriptors with defined physicochemical meaning. Mechanistic interpretation indicated that van der Waals surface area, presence of C-F at topological distance 6, heteroatom content and frequency of C-N at topological distance 9 are main factors responsible for the toxicity of NACs. This proposed model was successfully applied to a true external set (295 compounds), and prediction reliability was analysed and discussed. Moreover, the rat-mouse and mouse-rat interspecies quantitative toxicity-toxicity relationship (iQTTR) models were also constructed, validated and employed in toxicity prediction for true external sets consisting of 67 and 265 compounds, respectively. These models showed good external predictivity that can be used to rapidly predict the rat oral acute toxicity of new or untested NACs falling within the applicability domain of the models, thus being beneficial in environmental risk assessment and regulatory purposes.