Biomedical Engineering Reference
In-Depth Information
To address all these issues, the following approaches are necessary. First of all, proper and reli-
able experimental data for the series of related but different size NPs should be available for QSAR
analysis. It is vital to obtain consistent toxicological data, which will be used to develop QSAR
models for toxicity assessment. In addition, it is quite important to develop the nanomaterials' prop-
erty database-collected data on experimental physicochemical properties, biological activity, and
toxicity endpoints for various sizes of nanomaterials. Second, the structural and size descriptors
suitable for modeling NP reactivity have to be identified. These descriptors can be selected/adapted
from the available pool of descriptors designed for conventional (small) compounds or calculated
by applying quantum-mechanical (MD) methods, developed especially for NPs, or selected from
known experimental physical properties. The close connection and interaction among all these
areas—experimental toxicology, physicochemical NP characterization (nanodescriptor character-
ization), and computational nano-QSAR methods are essential for successfully understanding of the
mechanisms of toxicity of nanomaterials and proper risk assessment.
19.11 ECOTOXICITY OF NPs
To ensure a “safe” nanotechnology industry, the need for hands-on research in the area ecotoxi-
cology of nanomaterials has been emphasized [99]. Several assays for ecotoxicological testing of
nanomaterials have been developed. Various mechanisms that govern toxicity as well as usefulness
of bacterial systems to study toxicity of manufactured NPs have been explained. The suspensions of
C
60
have been shown to be toxic to bacteria [199], fathead minnows (
Pimephales promelas
) [200],
and zebrafish embryos [200]. SWCNT-based nanomaterials to an estuarine copepod (
Amphiascus
tenuiremis
),
Daphnia
, and rainbow trout have been reported [201-203]. The ecotoxicities of TiO
2
,
ZnO, and SiO
2
NPs suspended in water using
E. coli
and
Bacillus subtilis
as two model bacte-
rial species were compared and reported that ZnO was toxic to
B. subtilis
[204]. Experiments on
embryonic zebrafish demonstrated similar results; ZnO NPs were more toxic than TiO
2
for Al
2
O
3
NPs [205]. In a comprehensive study on the 48-h acute toxicity of water suspensions of six manu-
factured nanomaterials (i.e., ZnO, TiO
2
, Al
2
O
3
, C
60
, SWCNTs, and MWCNTs) to
Daphnia magna
,
using immobilization and mortality as toxicological endpoints, a dose dependence in acute toxicity
was demonstrated [206]. The suitability of fish hepatocyte cultures as a model system for investigat-
ing the cellular uptake of engineered NPs have been illustrated [207]. Another model system for
judging nanomaterials toxicity is zebrafish embryos; the model is also being useful for comparative
biology because of the similarities between the zebrafish and human genomes, early-life develop-
ment, and disease processes. In a study on ZnO toxicity in rodent lung and zebrafish embryos, data
indicated reduced toxicity in the latter system upon doping of Fe in ZnO [208].
The release of nanomaterials to the environment during recycling and disposal is of particular
concern for NPs incorporated into limited use and/or disposable products. Once released, these nano-
materials would readily undergo transformations via biotic and abiotic processes. Understanding
environmental transformations and the fate of engineered nanomaterials will enable the design
and development of environmentally benign nanomaterials, as well as their use as environmental
tracers, in environmental sensing and in contaminant remediation. This was demonstrated in a bio-
mimetic hydroquinone-based Fenton reaction that provides a new method to characterize transfor-
mations of nanoscale materials expected to occur under oxidative environmental conditions [209].
The current computational techniques are being used to study interactions of NPs with biological
systems and these have been reviewed in Ref. [210]. Such studies could also be used to complement
the experimental data on toxicity.
19.12 LIMITATIONS OF
IN VITRO
ASSAY IN TOXICOLOGY
In vitro
toxicity assays are primarily utilized to investigate the generic cytotoxicity or genotoxicity
of chemicals. While the traditional application of
in vitro
tests has been screening of chemicals,
