Biomedical Engineering Reference
In-Depth Information
TABLE 10.2
Summary of Selected
In Vivo
Carcinogenic Studies for Different Nanoparticles
NPs
Animals
Route
Result
References
TiO
2
Female rats
Inhalation
Lung tumors, benign and
malignant squamous, and
alveolar cell tumors combined
Heinrich et al. (1995)
Carbon black
Female rats
Inhalation
Lung tumors, benign and
malignant squamous cell
tumors, and bronchio-alveolar
cell tumors combined
Heinrich et al. (1995)
MWCNT
Male rats
A single intrascrotal injection
Disseminated mesothelioma in
the peritoneal cavity
Sakamoto et al. (2009)
SWCNT
Male rats
Intratracheal instillation
No tumors
Warheit et al. (2004)
components. The basis of this assumption is mechanistic considerations and a number of animal
studies using relatively high doses. Although some experimental evidences do prove that some
nanoparticles have a carcinogenic potential or higher carcinogenic potential compared to larger
particles of the same material, it is still hard to say whether nanoparticles are naturally carcinogenic.
In fact, current
in vivo
experiments have significant variations regarding the sample preparations
of nanoparticles, the way of administration, dosages, animal species, and experimental design, and
only a handful of the studies on select nanoparticles meet the standardization and quality criteria
necessary in order to consider them for regulatory assessments. On the other hand, it is inadequate
to consider the particle size alone when investigating the carcinogenic effect of nanoparticles. Other
factors, such as the interactions of nanoparticles with cellular structures and biomolecules, can also
result in toxic effects. Table 10.2 concludes a number of reports available to present a partial picture
of the potential carcinogens entering the market place. However, the carcinogenic risks of other
nanoparticles are still masked, as there is a lack of sufficient
in vivo
data.
10.4.4 p
redIcatIoN
of
I
n
V
IVo
t
oxIcIty
By
I
n
V
Itro
d
ata
In vitro
studies do not necessarily reflect the result of
in vitro
studies, but if simple high-throughput
assays have been developed and validated, ethical and economic problems in
in vivo
studies could
be avoided. A report from Rushton et al. (2010) evaluated two cell-free and two-cell-based assays
for their reliability in
in vivo
toxicity predications. The cell-free systems used fluorescence- and
electron spin resonance (ESR)-based assays of oxidant activity, while the cell-based systems used
ESR and luciferase assays.
In vivo
validation was conducted by acute pulmonary inflammatory
responses in rats. This group of scientists suggested that the A549 Luc1 cell line might be well
suited for use in a high-throughput assay.
10.5
IN SILICO
EVALUATION OF NANOPARTICLE TOXICITY
The use of computational models to predict the behavior of nanomaterials in biological systems is
promising, because they can avoid time-consuming and resource-intensive toxicological tests. The
integration of mathematical, statistical, modeling, and computer science tools provide a better under-
standing of the toxic mechanisms. Computational toxicology takes advantage of three modern tech-
niques: High-information-content data streams, such as microarray; novel biostatistical methods;
and computational data analysis (Rusyn and Daston, 2010). Computational approaches to toxicity
predications can be applied in various areas. The pharmaceutical industry can apply these models
to screen new compounds and eliminate the toxic effects of new chemical entities (Cronin, 2002).
