Modeling and mechanistic understanding of cytotoxicity of metal oxide nanoparticles (MeOxNPs) to Escherichia coli : categorization and data gap filling for untested metal oxides.

Metal oxide nanoparticles (MeO x NPs) production is expected to increase every year exponentially, and their potential to cause adverse effect to the environment and human health will also expand rapidly. Hence, risk assessment of nanoparticles (NPs) is necessary to design ecosafe products. However, experimental ecotoxicological assessments are time-consuming requiring a lot of resources. Therefore, researchers rely on alternative in silico approaches to predict the behavior of NPs in the biological system. Quantitative structure - toxicity relationship (QSTR) has been adopted as a potential method to predict the cytotoxicity of untested NPs. Hence, in the present study, multiple linear regression (MLR) models were developed using 17 MeO x NPs on Escherichia coli (E. coli) bacteria cells under both light and dark conditions. The models were developed applying Small Dataset Modeler software, version 1.0.0 (http://teqip.jdvu.ac.in/QSAR_Tools/DTCLab/) which generates models with a limited number of data points. Periodic table-based descriptors (both 1st and 2nd generation) were used for the modeling purpose. Two statistically significant MLR models based on photo-induced toxicity ( Q ( LOO ) 2 =   0.612 , R 2 = 0.726) and dark-based toxicity ( Q ( LOO ) 2 =   0.627 , R 2 = 0.770) were developed. From the developed models, we interpreted that increase in valency and oxidation state of the metal will decrease the cytotoxicity whereas the atomic radius of the metal and electronegativity of MeO x NPs influence the toxicity toward E. coli cells. The MLR models were validated using different internal validation metrics. Additionally, we have collected 42 MeO x NPs as an external set to observe the predictive power of the two developed MLR models and categorize them into toxic and non-toxic classes. The chemical features selected in the developed models are important for understanding the mechanisms of nanotoxicity. Thus, the developed models can be a scientific basis for designing safer NPs.