We have developed QSTR models for the toxicity of 384 diverse aromatic compounds to Tetrahymena pyriformis with recently introduced extended topochemical atom (ETA) indices and compared the ETA models with those derived from various non-ETA topological descriptors and also combined set of descriptors encompassing the ETA and non-ETA parameters. The data set was split into test (25% compounds of total data points) and training (remaining 75%) sets based on K-mean clustering technique. Different statistical analyses (factor analysis followed by multiple linear regression (FA-MLR), stepwise regression and partial least squares (PLS)) were performed with the training set compounds to develop QSTR models using the topological descriptors. All the developed models were cross-validated using leave-one-out (LOO) technique. The best models were selected on the basis of predicted R(2) values for test set compounds. The best models (based on external validation) developed from different techniques came from the combined set of descriptors. The above results indicate that the use of ETA descriptors with non-ETA descriptors improved the statistical quality of the non-ETA models. From the best models involving ETA parameters, it is observed that functionality of halogen atoms (hydrophobicity), volume parameter (bulk) and nitrogen containing functionalities (polarity) are important for developing QSTR models for the current data set. This study suggests that ETA parameters are sufficient power to encode chemical information contributing significantly to the toxicity of diverse aromatic compounds to T. pyriformis.