Environmental Engineering Reference
In-Depth Information
luminescence) [ 15 ]. Advanced kit like Nano-toolkit allows determination of con-
centration, size, chemical composition, density, route of exposure, time of expo-
sure, and the point of embryonic development at which the test material is
administered by using scoring system of 0 (normal phenotype); 1 (minor pheno-
typic changes); 2 (moderate alterations); 3 (severe embryo deformation); and
4 (embryo death).
6.3.5 Selection of Animal Model
Assessment of nanotoxicity can be done at (1) sublethal doses, (2) chronic doses,
(3) repeated doses, and (4) long-term doses. In animal experimentation, generally
rats, mice, rabbits and dogs are employed. The choice of correlative and predictive
models to assess acute and chronic toxicities is very essential in the development of
new therapeutics. However, there is still gap in deeper understanding and correla-
tion of physiochemical factors and pharmacological, toxicological screens, phar-
macokinetic and biodistribution pattern obtained in vivo. The causes of autophage
in animals after administration of nanoparticles are still unknown and literature
report involvement of Akt/mTOR pathway [ 16 ]. The toxicology of nanoparticles
when administered by non-inhalation route is very complex and needs interdisci-
plinary efforts to investigate pharmacological risk assessment at cellular and
biochemical levels. While respiratory tract has more than 40 different cell types,
type of cells, polarity, tight junctions, and other characteristics contribute to the
differences in biological/toxicological responses against inhaled particles besides
understanding of complicated pulmonary pathways.
Efficacy studies are mainly performed in mice and pharmakinetic and toxicity
studies in rats and dogs. To reduce time and investment involved in establishing
mammalian animal model for toxicity, Zebrafish (Danio rerio) model has been
involved in recent years because of its close homology with human genome and
immunologic response behaviorr [ 17 ]. Optimal clarity of zebrafish allows close
experimental watch on pathological processes in real time, such as organogenesis,
vasculogenesis, and deleterious effects during anatomical development during
nanoparticle treatment. Cost of maintenance and husbandry (200-300 eggs/day
for every 5-7 days) is very much less compared to the other animal model (3-6
months).
Another model, Xenopus, allows microsurgery at very minute level and can be
used as model for gene function testing. There is a database developed to assimilate
information on resources on use of Xenopus as model ( www.xenbase.org ) . For
in vivo angionesis testing, chicken embryo is widely used as model. Schweitzer A
rated animal models at scale of 1-5 depending upon their use in pharmacological
experiments: (1) low sensibility/consciousness: mollusks; (2) some sensibility:
cephalopods, fishes, amphibians; (3) sentient, but potentially limited in conscious-
ness: reptiles; (4) sentient and conscious: mammals, birds; (5) sentient, highly
intelligent and precognitive: primates, carnivores, cetaceans [ 3 ].
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