Multi-target QSTR modeling for simultaneous prediction of multiple toxicity endpoints of nano-metal oxides.

The metal oxide nanoparticles (MeONPs) due to their unique physico-chemical properties have widely been used in different products. Current studies have established toxicity of some NPs to human and environment, hence, imply for their comprehensive safety assessment. Here, the potential of using a multi-target QSTR modeling for simultaneous prediction of multiple toxicity endpoints of various MeONPs has been investigated. A multi-target QSTR model has been established using four different experimental toxicity data sets of MeONPs. Diversity of the considered experimental toxicity data sets was tested using the Kruskal-Wallis (K-W) statistics. The optimal validated model yielded high correlations (R2 between 0.828 and 0.956) between the experimental and simultaneously predicted endpoint toxicity values in test arrays for all the four systems. The structural features (oxygen percent, LogS, and Mulliken's electronegativity) identified by the QSTR model were mechanistically interpretable in view of the accepted toxicity mechanisms for NPs. Single target QSTR models were also established (R2Test >0.882) for individual toxicity endpoint prediction of MeONPs. The performance of the multi-target QSTR model was closely comparable with individual models and with those reported earlier in the literature for toxicity prediction of NPs. The model reliably predicts the toxicity of all considered MeONPs, and the methodology is expected to provide guidance for the future design of safe NP-based products. The proposed multi-target QSTR can be successfully used for screening new, untested metal oxide NPs for their safety assessment within the defined applicability domain of the model.