Table 2 Pathophysiology and toxicity effects of CNTs^a

ROS generation^a

Protein, DNA and membrane injury,^aoxidative stress^b

Oxidative stress^a

Phase II enzyme induction, inflammation,^bmitochondrial perturbation^a

Mitochondrial perturbation^a

Inner membrane damage,^apermeability transition (PT) pore opening,^aenergy failure,^aapoptosis,^aapo-necrosis, cytotoxicity

Inflammation^a

Tissue infiltration with inflammatory cells,^bfibrosis,^bgranulomas,^batherogenesis,^bacute phase protein expression (e.g., C-reactive protein)

Uptake by reticulo-endothelial system^a

Asymptomatic sequestration and storage in liver,^aspleen, lymph nodes,^bpossible organ enlargement and dysfunction

Protein denaturation, degradation^a

Loss of enzyme activity,^aauto-antigenicity

Nuclear uptake^a

DNA damage, nucleoprotein clumping,^aautoantigens

Uptake in neuronal tissue^a

Brain and peripheral nervous system injury

Perturbation of phagocytic function,^a“particle overload,’’ mediator release^a

Chronic inflammation,^bfibrosis,^bgranulomas,^binterference in clearance of infectious agents^b

Endothelial dysfunction, effects on blood clotting^a

Atherogenesis,^athrombosis,^astroke, myocardial infarction

Generation of neoantigens, breakdown in immune tolerance

Autoimmunity, adjuvant effects

Altered cell cycle regulation

DNA damage

Proliferation, cell cycle arrest, senescence

Mutagenesis, metaplasia, carcinogenesis