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Abstract: This study was undertaken to address the current deficient knowledge of cellular response to nanosized particle exposure. The study evaluated the acute toxic effects of metal/metal oxide nanoparticles proposed for future use in industrial production methods using the in vitro rat liver derived cell line (BRL 3A). Different sizes of nanoparticles such as silver (Ag; 15, 100nm), molybdenum (MoO3; 30, 150nm), aluminum (Al; 30, 103nm), iron oxide (Fe3O4; 30, 47nm), and titanium dioxide (TiO2; 40nm) were evaluated for their potential toxicity. We also assessed the toxicity of relatively larger particles of cadmium oxide (CdO; 1μm), manganese oxide (MnO2; 1–2μm), and tungsten (W; 27μm), to compare the cellular toxic responses with respect to the different sizes of nanoparticles with different core chemical compositions. For toxicity evaluations, cellular morphology, mitochondrial function (MTT assay), membrane leakage of lactate dehydrogenase (LDH assay), reduced glutathione (GSH) levels, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were assessed under control and exposed conditions (24h of exposure). Results showed that mitochondrial function decreased significantly in cells exposed to Ag nanoparticles at 5–50μg/ml. However, Fe3O4, Al, MoO3 and TiO2 had no measurable effect at lower doses (10–50μg/ml), while there was a significant effect at higher levels (100–250μg/ml). LDH leakage significantly increased in cells exposed to Ag nanoparticles (10–50μg/ml), while the other nanoparticles tested displayed LDH leakage only at higher doses (100–250μg/ml). In summary the Ag was highly toxic whereas, MoO3 moderately toxic and Fe3O4, Al, MnO2 and W displayed less or no toxicity at the doses tested. The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, reduced mitochondrial membrane potential and increase in ROS levels, which suggested that cytotoxicity of Ag (15, 100nm) in liver cells is likely to be mediated through oxidative stress. [Copyright &y& Elsevier]