Page 353 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

320 SECTION | III Nanoparticles, Radiation and Carcinogens

VetBooks.ir 12 (by BET surface area) Aluminum powder as-received
Laser diffraction sizing data from nominally 83nm

10

8 Rel volume % curve
Relative % 6 Rel number % curve

4
Rel area % curve
(Calculated)
2

0
0.10 0.1 1 10 100
Particle diameter (microns)
FIGURE 18.1 An example of relative abundance of particulate sizes in a sample.

manageable, exposures and effects, and are therefore dependent on multiple physical chemical factors other
expected to cause insignificant adverse health effects; than the familiar mass or concentration used in traditional
however, these assumptions may be difficult to substanti- toxicology. Another significant challenge is the dynamic
ate based on traditional assessment methods because the nature of the physicochemical characteristics of materials
effects of ENMs may be unique, product-specific, and at the nanoscale, which often change over time, and as a
unpredictable from data derived from larger particles or consequence of interaction with biological systems.
from chemicals in solution (Hoet et al., 2004; Tsuji et al., (Maynard et al., 2011). The specific changes that occur
2006). Studies have shown that some ENMs are not inher- and their implications for biological interaction depends
ently benign and that they may distribute throughout the on the specific nanomaterial. Metal oxide nanoparticles,
body, inducing inflammation, oxidative stress, and other e.g., may aggregate and agglomerate without significant
adverse effects (Nel et al., 2006). The results of studies reduction of the total surface area of the agglomerate, but
demonstrating ENM adverse effects should, however, be it may limit interaction with internal surfaces of the
interpreted with caution, especially when very high exper- agglomerate to substances that are small enough to pene-
imental doses are used that may not represent realistic trate the agglomerate (Pickrell et al., 2010). Thus, unique
exposure scenarios. Meaningful risk assessments should effects, associated with repeated and combined exposures,
address questions related to the identification of hazards, are expected to emerge. The formation of reactive oxygen
exposure assessment, and toxicokinetics including persis- species and resulting oxidative stress has emerged as an
tence in cells and subcellular structures (Oberdo ¨rster, important mechanism of toxicity of nanomaterials. The
2010). Assuming public acceptance, a toxicologist’s expe- specific mechanisms of free radical formation and oxida-
rience with past “miracle” materials advises us that cau- tive stress effects are, however, difficult to study in detail
tion in using novel substances without fully evaluating in vivo, and much of the current knowledge are derived
potential health risks may be ill advised (Hoet et al., from cell culture studies. Factors that appear to influence
2004; Tsuji et al., 2006). The discovery of serious adverse free radical formation include particle size, shape, aggre-
health effects, such as asbestos-like effects associated gation and surface chemistry, particle dissolution rate,
with multiwalled carbon nanotubes, has prompted nano- release of metal ions and oxides, UV light activation, and
toxicologists to recommend heightened caution in the cellular environment factors such as pH and inflammatory
release of ENMs until more adequate information responses (Fu et al., 2014). The complexity and multidi-
becomes available (Oberdo ¨rster, 2010). Moving forward, mensional nature of nanomaterial toxicity makes it neces-
the field of nanotoxicology is faced with many chal- sary to follow a comprehensive approach when
lenges, including the need to modify our understanding of performing nanotoxicity assessments, including physical
the concept of “dose,” which, at the nanoscale level, is characterization of nanomaterials, and studies to