Geoscience Reference
In-Depth Information
Table 3.3 Nanomaterial effects as the basis for pathophysiology and toxicity
Experimental NM effects
Possible pathophysiological outcomes
ROS generation
a
Protein, DNA and membrane injury
a
, oxidative
stress
b
Oxidative stress
a
Phase II enzyme induction, inflammation
b
,
mitochondrial perturbation
a
Mitochondrial perturbation
a
Inner membrane damage
a
, permeability transition
(PT) pore opening
a
, energy failure
a
, apoptosis
a
,
apo-necrosis, cytotoxicity
Inflammation
a
Tissue infiltration with inflammatory cells
b
, fibrosis
b
,
granulomas
b
, atherogenesis
b
, acute phase protein
expression (e.g., C-reactive protein)
Uptake by reticulo-endothelial system
a
Asymptomatic sequestration and storage in liver
a
,
spleen, lymph nodes
b
, possible organ enlargement
and dysfunction
Protein denaturation, degradation
a
Loss of enzyme activity
a
, autoantigenicity
Nuclear uptake
a
DNA damage, nucleoprotein clumping
a
, autoantigens
Uptake in neuronal tissue
a
Brain and peripheral nervous system injury
Perturbation of phagocytic function
a
,
''particle overload,'' mediator release
a
Chronic inflammation
b
, fibrosis
b
, granulomas
b
,
interference in clearance of infectious agents
b
Atherogenesis
a
, thrombosis
a
, stroke, myocardial
infarction
Endothelial dysfunction, effects on blood
clotting
a
Generation of neoantigens, breakdown
in immune tolerance
Autoimmunity, adjuvant effects
Altered cell cycle regulation Proliferation, cell cycle arrest, senescence
DNA damage Mutagenesis, metaplasia, carcinogenesis
a
Effects supported by limited experimental evidence;
b
Effects supported by limited clinical
evidence. From Nel et al. (
2006
). Reprinted with permission from AAAS
nanoparticles by Kupffer cells in the liver induces modifications in hepatocyte
antioxidants systems, probably due to the production of radical oxygen species
(Fernandez-Urrusuno et al.
1997
). Exposure of laboratory-grown human liver and
skin cells for 48 h to solutions containing 20 ppb of buckyballs demonstrated that
the solution could kill half the cells (Goho
2004
). Green and Howman (
2004
)
report the observation of DNA damage in plasmid nicking assays with water-
soluble CdSe/ZnS quantum dots (cadmium selenide capped with a shell of zinc
sulfide, complete with biotin surface functionality). Studies involving pulmonary
exposure of carbon nanotubes in rodents (Lam et al.
2004
; Warheit et al.
2004
)
suggest that lung histopathological responses, including inflammation and granu-
loma formation, may be significant. Nanoparticles can enter cells and cross the
blood-brain barrier where they may have unexpected health effects (Guzman et al.
2006
). The US EPA attributed 60,000 deaths per year to the inhalation of atmo-
spheric nanoparticles; and there is evidence for direct transfer into the brain
(Oberdörster et al.
2004
; Raloff
2003
). Table
3.3
summarizes the current knowl-
edge of the impact of nanomaterials in relation to pathophysiology and toxicity.
