Biomedical Engineering Reference
In-Depth Information
and potential risks, and for establishing specific parameters for facilitating skin absorption and the
establishment of safe exposure ranges, testing the possibility of nanoparticle accumulation in crev-
ices, hair follicles, and/or epidermis and underlying layers of connective tissues.
On the other hand, exposure to nanomaterials can also be unintentional. As the production and
usage of nanotechnologies increase, more nanoparticulates are expected to be released into the
environment. For example, because silver nanoparticles are increasingly being used as an antibacte-
rial in textiles, some of the nanoparticles end up in wastewater due to leaching during the washing
process [22]. In addition, it has already been demonstrated that nanoparticles are already present in
air pollution as a by-product of burning fuel and some manufacturing processes [23,24]. Repeated
concerns have been raised and investigated about the health implications of exposure to nanopar-
ticles in the environment and workplace. Specifically, air pollution presents a substantial source of
an assortment of particulates, including sulfate-, nitrate-, and carbon-containing particulates [25].
In the case of airborne particulates, size determines half-life and tissue penetration. Numerous sci-
entific studies have demonstrated that the size of the nanoparticle determines the location of deposi-
tion in the lungs, such that the smaller nanoparticles (1-10 nm) travel all the way to the alveoli where
they may be absorbed, whereas larger particles become trapped in the nasal cavity and larynx [26].
However, one of the largest challenges in the process of assessing the toxicological profile for
specific types of the nanoparticles is the development of accurate models; toxicology findings are
often inconsistent between
in vitro
and
in vivo
. The differences may be due to the high reactivity
of the nanomaterials, resulting in significantly more complex biointeractions
in vivo
as compared
with cell culture systems. Specifically, the complex microsystems of different cell types are diffi-
cult to mimic
in vitro
, as cell/cell and cell/matrix interactions, diversity of cell types, and complex
hormonal signaling are missing
in vitro
[27,28]. In addition, the interactions with nanoparticles may
differ
in vitro
, as
in vitro
tests are often quite static whereas nanoparticles are very mobile, often
translocating in the body and accumulating in specific locations such as tumors. However,
in vitro
assays offer a quick and cost-effective method for testing toxicological endpoints and allowing for
the deduction and testing of specific primary mechanisms involved without the ambiguity intro-
duced through physiological compensatory mechanisms [29]. Furthermore,
in vitro
testing allows
for the determination of primary effects without the secondary effects due to inflammation. Other
well-known benefits of the use of
in vitro
assays for toxicology studies include reproducibility, cost-
effectiveness, and the reduced amount of test materials required. Most importantly,
in vitro
toxicol-
ogy studies minimize the need for animal testing, and assist with identifying the areas and scopes
for improvements in subsequent
in vivo
studies, which are usually more expensive and with results
that may be more difficult to interpret [30]. On the other hand, the shortcomings of
in vitro
tests for
toxicological studies are reportedly nanomaterial interactions with the classical dye-based [31] and
fluorescence-based assays [32], especially in the case of using metal and magnetic nanoparticles
at high doses. The nanoparticle may interact with dyes such as 3-(4,5-dimethylthiazole-2-yl)-2,5-
biphenyl tetrazolium bromide (MTT), neutral red, and Coomassie blue among others, stabilizing
the structures by preventing solubilization, inducing chemical reactions and false-positives, and/or
absorbing the dye, resulting in erroneous reports [28]. If such interactions are suspected, alterna-
tive methods need to be utilized. Other available methods include commonly used assessments of
DNA damage such as the comet assay, Ames test, and chromosome aberration assays, among others
[33,34]. Other aspects contributing to toxicology are the induction of oxidative stress and inflam-
mation, which can also be assessed by biochemical assays. However, the interactions of assays with
the nanomaterial cannot be excluded in the case of DNA damage tests, oxidative stress, and inflam-
mation. Therefore, the inclusion of appropriate controls, both negative and positive, becomes more
important in ascertaining the absence of interference. Further, the usage of a battery of toxicity
assays testing different endpoints may improve the understanding of toxicity-inducing parameters
of the specific nanomaterials in question.
Although
in vitro
methods are faster, cheaper, more convenient, and do not involve ethical
issues,
in vitro
tests do not always provide satisfactory methods of toxicology assessment. Modeling
