**3. Entry of nanoparticles**

The exogenous entry of engineered NP is mainly from hand-to-mouth contact in the workplaces. Nanoparticles enter the body through food, drinking water, drugs, or exposure during medical procedures. Inhalation of airborne nanoparticles is also an important point of entry into the body [22]. Larger particles are trapped in the nasopharyngeal region (5–30 μm), while the smaller particles (1–5 μm) get deposited in the tracheobronchial region. These particles can be removed by mucociliary clearance. Finally, the remaining submicron particles (< 1 μm) and nanoparticles (< 100 nm) with the smallest size distribution penetrate deeply into the alveolar region, where removal mechanisms may be insufficient. Nanosized particles can reach the alveolar region of the lungs where they get in contact with the alveolar epithelium. From the alveolar epithelium these particles can cross the blood-air-tissue barrier and enter the bloodstream to reach various organs [22]. Inhaled ultrafine particles may get deposited in the olfactory mucosa from where they can translocate in the central nervous system (CNS), which in turn might cause neurotoxicity. Studies have shown that the CNS may be a crucial target for nanoparticle inhalation or intranasal installation exposure [23, 24]. The third route of entry of NP into the body is through dermal penetration [22, 25].

The NPs enter the CNS through three main routes: (1) Transport through the lymphatic and circulatory system; (2) Activity of the mucocilliary escalator followed by oral exposure; and (3) Transport through the olfactory and trigeminal nerves [18, 26]. This pathway involves the passage of nanoparticles through the olfactory epithelium and the neurons associated with it to the brain [18]. Carbonaceous nanomaterials have been reported to show increased access to the brain via the facilitation of olfactory mucosa and olfactory nerve [23]. After uptake, NPs can permeate into other parts of the brain by simple diffusion and then travel along the direction of the convection of the interstitial fluid and the cerebrospinal fluid flow [27].
