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react with the atmosphere to produce a less volatile compound, which then condenses into solid or liquid particles. Just about any combustion will generate a cloud of nanoparticles. For example, Figure 2.3 shows the particles generated by a “nightlite” type candle. Burning petrol and diesel also generate nanoparticles so in urban areas this is a major source. A particular issue is diesel engines, which generate most of their nanoparticles from sulfur contained in the fuel. A massive worldwide effort to reduce the level of sulfur in diesel and thus the number of nanoparticles produced has brought down the concentration from 5000 ppm before 1993 to 10 ppm today.

      The effect on the body of exposure to nanoparticles is a hot topic in the debate on the benefits/hazards of nanotechnology, but there is limited hard information to inform the discussion. It is worth emphasizing that life on this planet evolved in a dense cloud of naturally occurring nanoparticles and we have been exposed to nanoparticles produced by human activity since the invention of fire. In addition, industrial activity based on certain types of nanoparticles, for example, carbon black, has been around since early civilizations. The difference now is that new nanotechnology industries will produce nanoparticles composed of a wide range of different materials as well as other forms of “nanomaterial” such as carbon nanotubes (see Chapter 3). Whichever way the nanoparticles enter the body, there is a highly developed immune response to clear them in the same way that any foreign invaders, including bacteria and viruses are removed. The clearance mechanisms are described in Chapter 8, Section 8.1.2, but the end result is that nanoparticles are passed out of the body via the feces or the urine. As we will see in Chapter 8, which describes medical applications of nanoparticles, keeping them in circulation for long enough to carry out their therapeutic or diagnostic function can be a problem. Here, the potential health risks of accidentally ingested nanoparticles will be discussed. There are three general surfaces in the body that act as interfaces, that is, the lungs, intestines, and skin and each will be considered.

      

      2.2.1 Entry Via the Lungs

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      Source: Patrick J. Lynch https://commons.wikimedia.org/wiki/File:Bronchial_anatomy.jpg. Licensed under CC BY 2.5.

      (b) Alveolar macrophages, typically 10 μm across that occupy the lungs and the alveoli. They ingest particles by phagocytosis and are carried up through the lung system by a slow mucus flow called the mucociliary escalator. They are eventually swallowed and pass out through the digestive system.

      Source: Reproduced with permission from [4].

      Since humans have evolved in the presence of atmospheric aerosols, the body has well‐developed mechanisms to cope with inhaled particles including nanoparticles. Dispersed throughout the airways of the lung right down to the alveoli are specialized cells with typical sizes of around 10 μm known as macrophages (Figure 2.4b). These are able to ingest particles using a mechanism (phagocytosis) in which the cell wall of the macrophage envelops the foreign body and passes it through to the interior. The cells are passed, with their cargo of absorbed particles, to the top of the lungs by a gradual upward drift of mucus, called the mucociliary escalator, so they can be swallowed and passed out through the digestive system. It typically takes the escalator about 70 days to clear a particle from the deepest part of the lungs through this time increase if the number of particles starts to overwhelm the macrophages. Particles deposited near the top of the airway can also adhere directly to the mucus and be removed by the mucociliary escalator.

      Inhaled nanoparticles can also affect parts of the body away from the lungs and cardiovascular disease is one well‐known consequence of their inhalation [8]. One hypothesis for the cause is that the particles produce inflammation within the lungs that results in the systemic release of cytokines. These are small proteins involved in cell signaling and regulation of the immune system and their release can have adverse side effects on the cardiovascular system. Another important mechanism that allows nanoparticles, especially those near the bottom end of the size scale (5–10 nm), to have a systemic effect is that they are able to translocate. That is, they pass through the alveoli into the blood circulation and are then deposited around the body.

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