Biomedical Engineering Reference
In-Depth Information
Toxicity assessment
-Uptake, distribution,
metabolism, and excretion
-Reactivity
-Dosimetry
Hazard identification
-Chemical composition
-Particle size
-Structure/properties
-Coatings
Risk characterization
-Likelihood of effects
-Nature of effects
-Effectiveness of controls
Exposure assessment
-Particle behavior
-Product uses,
durability
-Receptor
-Routes of entry
FIGURE 19.4 Risk assessment framework for nanomaterials. (From Tsuji JS et  al. Toxicology Science
2006;89:42-50. With permission.)
Identification of hazards depends on the diverse characteristics of these particles. Hazards of
novel structures will be less predictable than smaller-scale substances (e.g., metal oxides such as
TiO 2 or ZnO). Encapsulation of the material either by surface coatings or within a matrix affects
the reactivity and biological mobility of NPs [51], but the durability of such encapsulation needs to
be considered.
Exposure assessment includes the entire life cycle of nanomaterials from synthesis to disposal.
Exposure is likely the highest for workers, although product-specific evaluations should consider
consumer uses, wear, disposal, and potential for environmental release and fate for products contain-
ing nanomaterials. Several nanomaterials (e.g., CNTs, metal oxides) tend to aggregate, which may
reduce their ability to penetrate membranes, reach deep airways, or disperse. However, aggregation
by fullerenes in water has been associated with increased solubility and antibacterial properties [52].
The inhaled nanocarbon particles in humans readily pass into systemic circulation, where they
are a concern for cardiovascular toxicity. Iridium NPs administered to rats by the endotracheal tube
were cleared by the airways to the GIT and eliminated, with <1% translocating to other organs [53].
For systemically absorbed particles, the liver may be a primary translocation site with spleen, bone
marrow, heart, kidney, bladder, and brain as secondary sites [5].
The primary mechanism of action by inhalation or dermal routes appears to be free radical gen-
eration and oxidative stress associated with surface reactivity [5]. Oxidative stress associated with
TiO 2 NPs, for example, results in early inflammatory responses such as an increase in polymorpho-
nuclear cells, impaired macrophage phagocytosis, and/or fibroproliferative changes in rodents [54].
An inverse relationship has been observed between lung clearance rate and nano P25 TiO 2 tox-
icity in rodent species (i.e., order of increasing clearance and decreasing lung toxicity in a 90-day
inhalation study: rats > mice > hamsters) [54]. Lung clearance of particles in humans is greater than
in rats. Moreover, lung cancer in rats exposed to high levels of inert particles is thought to occur by
a lung-overload mechanism that is not relevant for humans [55]. On the other hand, translocation
to other organs may be a greater concern for humans. Such species differences are a concern in
extrapolating results from animal models to humans [55].
Intratracheal inhalation studies in rats indicate that ultrafine or nano TiO 2 is less inflammatory
than quartz, nickel or cobalt, or carbon black [56]. Studies in humans exposed to ZnO metal fumes
(including nanoscale particles) have shown a relatively low order of toxicity associated with signs
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