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Figure 1: Prooxidant pathway for NP-induced toxicity: various NP exhibit oxidative stress dependent toxicity. Upon NP exposure, ROS generation is capable of inducing oxidative DNA damage, strand breaks, protein denaturation, and lipid peroxidation thereby demonstrating the mutagenic and carcinogenic characteristics associated with NP. Excess free radical production leads to mitochondrial membrane damage causing necrosis and cell death. Phagocytes including neutrophils and macrophages generate massive ROS upon incomplete phagocytosis of NP through the NADPH-oxidase enzyme system whereas NP-induced ROS triggers an inflammatory cascade of chemokine and cytokine expression via activation of cell signaling pathways such as MAPK, NF-κB, Akt, and RTK. Furthermore, oxidative stress mediated stimulation of these cellular mechanisms results in transcription of genes responsible for fibrosis, EMT, and carcinogenesis. NP-elicited ROS is at the center stage for majority of the ensuing adverse outcomes.