Environmental Engineering Reference
In-Depth Information
were instilled into the rat lung at different mass doses in order to generate a range
of surface area doses. The data generated suggested a straight-line relationship
between surface area instilled and the infl ammation generated (Duffi n et al. , 2002,
2007). Furthermore, we also included alpha-quartz, a particle with a highly reactive
surface, known to be very potent at inducing pulmonary infl ammation leading to
fi brosis (silicosis) and lung cancer. This pathogenic particle induced a much larger
infl ammatory reaction that was above the straight line for the low toxicity low solu-
bility materials, suggesting that ability to induce infl ammation is a function of both
surface area and surface reactivity (Duffi n et al. , 2002, 2007 ).
Solubility is also likely to be very important in determining toxicity of particles.
If a nanoparticle is soluble then it will obviously release its resultant components.
If these components are not toxic and the dissolution is relatively rapid (up to a
few hours) then such a particle is unlikely to induce any signifi cant toxicity or health
effects. However, if the particle contains toxic materials, such as the cadmium in
quantum dots, then toxicity could be related to the release of toxic solutes. The
small size of the particles may mean that the particles dissolve quickly releasing a
bolus dose of the toxin. However, note that smaller size and larger surface area do
not always mean greater rate of dissolution (Chapter 3). In addition, if a nanopar-
ticle is soluble, the removal of solutes by blood or tissue fl uid may be suffi ciently
high to prevent concentrations reaching a toxic dose within any particular region
of the body. However, it is also worth noting that many particles are ingested into
cells by phagocytosis, allowing them to accumulate within intracellular structures
such as endosomes or lysosomes, resulting in confi ned release of solutes allowing
concentrations of solutes to accumulate. This could be further enhanced by the low
pH of cellular components such as the lysosome. All of this is currently supposition,
but it illustrates that solubility is likely to play a complex role in determining
nanoparticle toxicity.
As described for asbestos and high aspect ratio nanoparticles, the shape
of nanoparticles is also likely to be important in infl uencing toxicity. However, in
addition to fi bre-like dimensions and length, rigidity is also important. A long but
fl exible nanotube may be relatively easy to clear if it will fold up inside a cell,
whereas a rigid nanotube is more likely to exhibit fi bre - like properties (Brown
et al. , 2007b ).
It is now important to determine which of the physico-chemical characteristics
of nanoparticles are most associated with their biological effects (Figure 9.2). As
outlined previously, an understanding of this relationship can be used to predict
toxicity and prevent the requirement for toxicity testing of all types of
nanoparticles.
This process would be enhanced by the access of toxicologists to a bank of well
characterised reference materials. This would allow comparisons to be made
between laboratories and, once a database of information is generated in relation
to the reference material toxicity, comparison between particles. A list of suggested
reference materials has been proposed by the UK Government Department of the
Environment, Food and Rural Affairs (Defra) funded project, REFNANO (Aitken
et al. , 2008). The particles included in this list were chosen because of their relevance
to industry and therefore potential for exposure.
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