Biomedical Engineering Reference
In-Depth Information
19.9.2 Stress Response .................................................................................................... 405
19.9.2.1 Detection of ROS ................................................................................ 405
19.9.2.2 Glutathione Measurement ...................................................................406
19.9.2.3 Lipid Peroxidation Assay ....................................................................406
19.9.2.4 Nitrite Production ...............................................................................407
19.9.2.5 Mitochondrial Membrane Potential Dissipation Assay ......................407
19.9.3 Inflammatory Response ....................................................................................... 407
19.9.4 Genotoxicity .........................................................................................................407
19.9.4.1 Comet Assay .......................................................................................408
19.9.4.2 F
pg
-Modiied Comet Assay .................................................................408
19.9.4.3 Ames Test ........................................................................................... 408
19.9.4.4 Alkaline Single-Cell Microgel Electrophoresis Assay .......................408
19.9.4.5 DNA Damage .....................................................................................409
19.9.5 High-Throughput Screening Method ...................................................................409
19.9.6 Dose-Response Assessment .................................................................................409
19.10 Application of Computational Approach for Risk Assessment..........................................409
19.10.1 Molecular Modeling Methods .............................................................................409
19.10.2 Quantitative Structure-Activity Relationships for Nanomaterials ...................... 410
19.11 Ecotoxicity of NPs ............................................................................................................. 411
19.12 Limitations of
In Vitro
Assay in Toxicology ...................................................................... 411
19.13 Challenges for NPs
In Vitro
Test Met ho d s ......................................................................... 412
19.14 European Union Approach to Nanomaterial Risk Assessment ......................................... 413
References ...................................................................................................................................... 413
19.1 INTRODUCTION
Nanomaterials have a wide range of emerging applications in biomedical, pharmaceutical, and bio-
technological fields including biosensors, biomarkers, cancer therapy, deoxyribonucleic acid (DNA)
delivery systems, drug-delivery systems, enzyme immobilization, gene delivery, tissue engineering,
and as probes for confocal and electron microscopy [1].
Nowadays, nanotechnology-based products that claim the use of nanomaterials, are widely avail-
able in the market lists various products, including paint, cosmetics, personal-care products, and
food supplements. However, the presence of nanoscale entities in these products has not been veri-
fied. The human exposure to nanomaterials may involve inhalation, ingestion, and dermal routes.
These particles may also be directly injected into the human body for medical purposes. Once the
nanoparticles (NPs) appear to the systemic circulation, the NPs may be capable of distributing to
most organ systems and may even cross biological barriers, such as the blood-brain and blood-
testis barriers [2]. Since the number of applications of nanomaterials is expected to rise even more
in the future, long-term exposure and potential accumulation of these nanomaterials in the human
body may result.
With the ongoing commercialization of nanotechnology products, human exposure to NPs will
dramatically increase and an evaluation of their potential toxicity is essential. NPs applying for
biomedical and pharmaceutical purposes must satisfy rigorous toxicity screening to obtain approval
from regulatory authorities for use. The requirement to provide adequate biocompatibility pro-
files has led to renewed and increased interest in nanotoxicology research. Recently, a number
of manufactured NPs have been shown to cause adverse effects
in vitro
and
in vivo
[3]. NPs have
unique physicochemical properties attributed to their extremely small size, and possess extremely
high surface-area-to-volume ratio that renders them highly reactive. High reactivity could poten-
tially lead to toxicity due to harmful interactions of nanomaterials with biological systems and
the environment [4]. It has been shown that the NPs of TiO
2
induced a much greater pulmonary-
inflammatory response than larger particles of the same chemical content at equivalent mass
