Consensus models to predict oral rat acute toxicity and validation on a dataset coming from the industrial context

We report predictive models of acute oral systemic toxicity representing a follow-up of our previous work in the framework of the NICEATM project. It includes the update of original models through the addition of new data and an external validation of the models using a dataset relevant for the chemical industry context. A regression model for LD50 and classification model for toxicity classes according to the Global Harmonized System categories were prepared. ISIDA descriptors were used to encode molecular structures. Machine learning algorithms included Support Vector Machine (SVM), Random Forest (RF) and Naïve Bayesian. Selected individual models were combined in consensus.

The different datasets were compared using the Generative Topographic Mapping approach. It appeared that the NICEATM datasets were lacking some relevant chemotypes for chemical industry. The new models trained on enlarged data sets have applicability domain (AD) sufficiently large to accommodate industrial compounds. The fraction of compounds inside the models’ AD increased from 58 % (NICEATM model) to 94 % (new model). Yet, the increase of training sets only slightly improved of the models’ prediction performance: RMSE values decreased from 0.56 to 0.47 and balanced accuracies increased from 0.69 to 0.71 for NICEATM and new models, respectively.