Environmental Engineering Reference
In-Depth Information
taBlE 30.2
Blood clinical measurements
Hematology
Clinical chemistry
Red blood cell count (RBC)
Sorbitol dehydrogenase (SdH)
Mean corpuscular volume (MCv)
Alkaline phosphatase (ALP)
Hemoglobin (Hb)
Creatine kinase (CK)
Hematocrit
Creatinine
Mean corpuscular hemoglobin (MHC)
Total protein
Mean corpuscular hemoglobin concentration (MCHC)
Albumin
Erythrocyte morphologic assessment
Blood urea nitrogen (BUN)
Leukocyte count (WBC)
Total bile acids
Leukocyte differential
Alanine aminotransferase (ALT)
Reticulocyte count
glucose
Platelet count and morphologic assessment
Cholesterol
Triglycerides
consumption is measured and recorded weekly. In 2-year study procedures, individual animal body weights for test and control
group animals are recorded on day one of the test and at 4-week intervals thereafter except for dosed-feed and dosed-water
studies, in which these are recorded weekly for the first 13 weeks and monthly thereafter [70].
Additionally, specific toxicological parameters can be evaluated and processed for hematology and clinical chemistry determi-
nations. Blood is collected from core study mice at the end of the study for hematology determinations (TableĀ 30.2). Other studies
such as micronuclei determinations in blood cells, genotoxicity, sperm morphology, and vaginal cytology evaluations are also used.
Another type of studies includes immunotoxicology probes. Assessment of the adverse effects on the immune system is an
important component for evaluating the overall health and safety of NMs. The immune system is constantly functioning to
maintain homeostasis, eliminating pathogens and removing cancerous cells. Small modifications to the immune system, which
may occur following NM exposure, could lead to impaired protection or inappropriate immune response resulting in autoim-
munity and damage to the host [72]. The most common effects include an increased susceptibility to infections or cancer, auto-
immune diseases, chronic inflammation, or allergies. There are large spectrums of
in vitro
and
in vivo
immunological assays in
comprehensive immunotoxicity studies. These include assays of immunochemistry (quantification of cytokines), immunoge-
nicity (antibodies), immunopathology (relative weight and histopathology of lymphatic organs), immunophenotyping (analysis
of cell origin), functional test (analysis of macrophage and granulocyte functions), hypersensivity testing, infection models
(bacterial, viral, fungal models), and asthma models.
For example, Lee evaluated the immunotoxicity of silica nanoparticles
in vivo
[30]. These nanoparticles have been used in
chemical mechanical polishing, varnishes, cosmetics, food, and biomedical devices. Although silica is generally considered to
be noncytotoxic, designing silica as NMs may change its biocompatibility because of the changes in its physicochemical prop-
erties. In an
in vivo
assay, animals received silica nanoparticles suspended in distilled water for 4 weeks (5 days/week). The
results indicated that
in vivo
exposure to silica nanoparticles caused damage to systemic immunity through the dysregulation of
the spleen, but the
in vivo
data were inconsistent with
in vitro
data, which showed lower cytotoxicity for silica nanoparticles.
This is an example of the importance of verifying biocompatibility both
in vitro
and
in vivo
during the design of new NMs and
therefore data from
in vitro
studies require verification through animal evaluations [30].
On the other hand, in humans, the most critical exposure routes for NMs are inhalation and skin contact, although the
adverse effects are mainly expected to occur in the lungs [73]
. In vivo
, there are combinations of particle delivery techniques
such as intratracheal instillation/aspiration/inhalation or nose-only/whole-body inhalation that could be used as a means to
study the pulmonary and systemic effects of nanoparticles. The evaluation of respiratory tract toxicity from airborne materials
frequently involves exposure of animals via inhalation. This provides a natural route of entry into the host and, as such, is the
preferred method for the introduction of toxicants into the lungs. However, for various reasons, this technique cannot always be
used, and the direct instillation of a test material into the lungs via the trachea has been employed in many studies as an
alternative exposure procedure.
For example, Horie and coworkers [74] evaluated the pulmonary toxicity of MWCNTs by intratracheal instillation in rat.
The MWCNT dispersion was administered to rat lung by single intratracheal instillation at doses of 0.2 mg and 0.6 mg/rat.
Bronchoalveolar lavage fluid (BALF) was collected at 3 days, 1 week, 1 month, 3 months, and 6 months after instillation. They
found that the intratracheal instillation of MWCNTs induced persistent inflammation in rat lung not only in the high-dose group
but also in the low-dose group [74].