**3. Nanoparticles as contaminants**

One characteristic that differentiates nanoparticles from other materials is that their small size and large surface to volume ratio give them unique properties in terms of their interaction with organisms, affecting how these materials translocate through the biological barriers (membranes). This property can be very useful for biomedical applications; however, it has been described [6, 19] that significant toxic effects can be observed due to the passage of nanoparticles to compartments unreachable by materials of larger dimensions. This is a consequence not only of their small size but also of their permeability, their large surface area and their tendency to form agglomerates [3]. This is a major problem given that inhaled nanoparticles not only enter the lungs but also there is evidence of their passage through the nasal mucosa, which may imply access to the central nervous system (CNS) with all the consequences that this entails.

One of the materials that have been studied concerning CNS toxicity are magnetite nanoparticles (Fe3O4); it has been observed that they can affect microvascular endothelial cells that form the BBB and can induce cell damage even at the mitochondrial level [19]. Damage at the mitochondrial level in the CNS could affect the cell cycle and regulation of apoptosis, making the organism more prone to cancer, neuronal dysfunction, and demyelination.

Another issue regarding nanoparticles, either from environmental pollution or derived from anthropogenic activities, is that they can damage the nasal epithelium after constant exposure, generating high rates of dysplasia in nasal tissues and inducing the accumulation of P53 protein, which in turn leaves the brain unprotected since the membranes lose their integrity and increase their permeability facilitating their passage through the nasal epithelium [20–22]. Exposure to environmental pollutants can also lead to BBB alteration, degeneration of cortical neurons, apoptotic glial cells, apolipoprotein E deposition in muscle cells and in pericytes, non-neuritic plaques and neurotropic tangles [23]. Therefore, exposure to this type of nanoparticles may initiate damage that leads to the development of neurodegenerative pathologies even at an early age [20, 21].

In this sense, it is relevant that oxidative stress damage, DNA damage and the presence of amyloid plaques in the olfactory bulb, frontal cortex and hippocampus, as a consequence of particulate matter and ozone present in environmental pollution, have already been clinically evidenced; microglia activation, inflammation, oxidative stress and changes in the BBB are the main mechanisms that lead to CNS pathology

and therefore neurodegenerative disorders such as ischemia, Parkinson's disease and Alzheimer's disease could be associated with such exposure [23].

It is evident that nanoparticles, both natural and derived from anthropogenic actions, can have a negative impact on the human organism. This impact can represent a high cost for the global health system, and that research aimed at understanding the mechanisms must be facilitated, in order to design strategies that allow us to avoid damage, but also to take advantage of the properties to design nanomaterials that can provide benefits, reduce costs for the health sector and increase the quality of life of people, thus becoming applied for the benefit of society.
