Human Toxicology and Effects of Nanoparticles - Environmental and Human Health Impacts of Nanotechnology - page 357

It is worth noting that many or most humans deal well with particle inhalation
due to evolutionary adaptations which have resulted in protective mechanisms
that clear particles from the lung surface. Physical removal from the respiratory
system involves two possible mechanisms. The lung consists of a series of branching
tubes (airways) that terminate in sacs (alveoli). The airways are lined with epithelial
cells, which are covered in hair-like cilia and thick, sticky mucus. The cilia continu-
ally beat and therefore move the mucus up and out of the lung to either be blown
from the nose or swallowed into the stomach. This process is known as the muco-
ciliary escalator. Particles depositing in the airways become trapped in the mucus
and are therefore cleared. The epithelium of the alveoli is not ciliated and particles
depositing in this deeper part of the lung have to be cleared by cells from the
immune system. Such cells include macrophages, which have the ability to move
from blood into the lung tissue and then into the airspaces. Once in the alveoli
the macrophage cell identifi es the ' foreign ' particle and ingests it by a process
known as phagocytosis. If the particle cannot be digested by the cell, then it is
physically removed by movement of the macrophage, either on to the mucociliary
escalator or by transport to the lymphatic system (Donaldson et al. , 2001a ). The
consequence of movement of different particle types to the lymph nodes is not well
understood.
Particle size infl uences the site of deposition of particles within the respiratory
system. Particles between about 2.5 and 10 m in size deposit in the airways

and are therefore cleared by the mucociliary escalator. Particles below 2.5

µ

m
can deposit throughout the entire respiratory system and are therefore
cleared by a combination of macrophage activity and the mucociliary escalator.
This means that ultrafi ne or nanoparticles when inhaled can deposit anywhere
in the respiratory system. It is important to realise that the enhanced respiratory
toxicity of ultrafi ne or nanoparticles is not solely because they reach the
alveolar regions of the lung. For example, in the study by Oberdorster' s group,
250 nm TiO 2 particles did not induce infl ammation, while the 25 nm particles
did; both particles deposited in the same region of the lung as they both possessed
a mean aerodynamic diameter of 1

µ

m. This means that there is some factor
other than site of deposition that makes ultrafi ne or nanoparticles more reactive
in the lung than larger particles. The same is true for carbon black and polystyrene
beads.
Since carbon black is made by the combustion of organic material, trace con-
taminants of polyaromatic hydrocarbons or transition metals can be found in some
samples. For the studies in which nanoparticle carbon black was used to induce
infl ammation in the rat lung, the potential involvement of contaminants was exam-
ined by making an aqueous extract of the particles. This extract failed to induce
any signifi cant infl ammation in the rat lung; furthermore, in vitro it did not exhibit
reactive oxygen species (ROS; oxygen containing molecules that have unpaired
electrons) production or induce calcium signalling in macrophages (Brown et al. ,
2000), as had been shown for carbon black (Stone et al. , 2000b ) (see below). This
was clear evidence that the activity of these particles did not lie in a soluble com-
ponent of the carbon black particle preparation.

µ