Environmental Engineering Reference
In-Depth Information
9.5
Suggestions for Future Study Designs
There are many considerations when designing a toxicity study for nanoparticles.
This chapter will not outline all of these considerations but will fi nish by highlight-
ing some key design factors that should be considered.
(i) The use of appropriate controls . It is obvious that all studies should
include controls such as a negative control (untreated animal or cells),
but other controls are also worth considering. For example, is there a positive
control that is known to induce the effect that you are looking for? Better
still, is there a particle that is known to induce this effect? Regarding negative
controls, it might also be worth considering a particle as a negative control,
perhaps a larger particle of the same chemical composition if this is
available.
(ii) Particle preparation . This is a big problem, and is anticipated to be an active
area of research over the next few years. Our current understanding of routes
of exposure is relatively poor, and this impacts on our ability to design appro-
priate exposure protocols. We may not be exposed to monodispersed versions
of the nanoparticle tested and so it may not be necessary to go to extravagant
lengths to generate a monodispersed suspension. When adding particle to
organisms or cells, should we used a reagent to aid dispersion? Proteins such
as those found in serum seem to be pretty effective in aiding particle disper-
sion and, of course, this is relevant for any nanoparticle gaining access to the
body, especially the blood (Sager et al. , 2007 , Foucaud et al. , 2007). If a particle
is prepared in a formulation prior to use then it might also be more appropri-
ate to check the particle toxicity dispersed in the formulation rather than the
pristine particles. Whatever the fi nal decision, it is important to make these as
relevant to real life as is possible.
(iii) Susceptibility . As shown for air pollution particles, individuals with pre-exist-
ing infl ammatory diseases are more susceptible to induction of morbidity and
mortality following exposure. Many of the toxicology models used currently
employ healthy models, and so it is important to consider more appropriate
models in the future. This is of course diffi cult, but models of cardiovascular
disease, such as the ApoE mouse, are now available.
(iv) Dose . The dose of nanoparticles that should be used in toxicology studies is
diffi cult in the absence of exposure information. However, we do have infor-
mation about the respiratory toxicity of particles such as PM 10 , quartz and
asbestos and these can, until such time exposure information is available, be
used as guidance to allow benchmarking of particle potency.
9.6
Conclusions
This rapidly evolving fi eld is still in its infancy. Over the next decade it can
be anticipated that signifi cant advances will be made in terms of understanding
the factors that infl uence and drive nanoparticle toxicity or safety. However,
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