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Toxicity of Nanomaterials Chapter | 18 321

VetBooks.ir determine nanomaterial behavior at cellular and organis- chemicals will slow solvation (Powers et al., 2006).
Solubility of ENMs is inversely correlated with their bio-
mal levels (Caballero-Diaz and Cases, 2016).
persistence. Since solubility and chemical reactivity are
NANOMATERIALS CHARACTERIZATION strongly dependent on the physical chemical environ-
ment, they should be measured in an environment as near
The unusual physicochemical properties of ENMs are to that of the target biological environment as possible.
attributable to their morphology, composition, and surface This can sometimes be accomplished with in vitro condi-
characteristics. In an effort to standardize the description of tions closely simulating biological solutions (Powers
nanomaterials in a way that will reduce uncertainty in data et al., 2006). Specific interactions may be present in bio-
interpretation and facilitate cross-comparison between studies, logical fluids that are absent in simple solvents. For
the Minimum Information on Nanoparticle Characterization example, when determining solubility and reactivity in
(MINChar) initiative (MINChar Initiative, 2008) identified a the lung, it is important to consider not just solubility in
list of parameters that should ideally be characterized during water, but in fluids that bear significant resemblance to
studies. The parameters include particle size and size distribu- that of the epithelial lining fluid (ELF). A minimal ELF
tion, agglomeration state and aggregation, particle shape, volume is predicted at 40 100 mL for mature humans.
chemical composition, crystal structure, surface composition, The pH varies from 6.9 at the end of inspiration, to 7.5 at
purity and levels of impurities, surface area, surface chemistry the end of expiration. Bicarbonate acts as a buffer, and
(including reactivity and hydrophobicity), and surface charge. the change in pH is caused by removing CO 2 of expira-
It was also recognized that the characteristics of ENMs may tion (Langmuir, 1965). Bicarbonate concentration in lung
not be stable during storage, handling, preparation, and deliv- simulant fluid increases the solubility of MgO (Pickrell
ery into biological systems. Since the media used for delivery et al., 2009). Surprisingly, macrocrystalline (bulk) MgO is
may change ENM properties, particular emphasis should be dissolved as extensively as nanosized MgO in lung stimu-
placed on characterization of ENMs “as administered.” It was lant fluids in about 10 20 min (Pickrell et al., 2009).
also recommended that responses should be interpreted against This paradoxical result suggests that bicarbonate chemical
a range of dose metrics, including mass, surface area, and activity may have a direct relation to the rapid dissolution
number concentration. of MgO in lung simulant fluid related to its modest solu-
Particles or particle agglomerates are usually not per- bility in distilled water. Stoichiometry of the likely chemi-
fect spheres and are almost never singly dispersed. cal species suggests a conversion of MgO to Mg (OH) 2 in
However, particle size is most often defined as the diame- aqueous media and a subsequent conversion to the
ter of a sphere that is equivalent in the selected property hydrated carbonate (Langmuir, 1965; Pickrell et al.,
to the particle measured; this makes it possible to conve- 2010). These phenomena serve to illustrate the potential
niently plot size distributions of irregularly shaped parti- error associated with studies conducted in simple solu-
cles or particle-agglomerates using a single value tions when attempting to predict activity in complex bio-
(diameter) along a single axis. The properties most often logical systems.
described are volume or mass; i.e., the diameter of a
sphere of equal volume or mass to the particle(s) in ques-
tion (volume or mass diameter). ANIMAL OR TISSUE EXPOSURES
The changes in ENM surface characteristics following
In Vitro Exposures to Nanomaterials
delivery into a biological system are of particular impor-
tance when biological interactions are assessed. Proteins Early indicators for ENP-derived adverse health effects
attach selectively to nanoparticle surfaces to form were needed for an adequate assessment cytotoxicity of
nanoparticle-protein coronas. This process, which depends different types of well characterized ENPs; cytotoxicity
on the adsorption properties of nanomaterial surfaces (Xia was used to infer relative risk (Brunner et al., 2006). For
et al., 2010), can dramatically change particle surface this purpose, the authors chose a mesothelioma and a
characteristics and, consequently, interactions with bio- fibroblast cell line. Two assays were performed. The first
logical systems. Combination with biological macromole- was mean culture activity, indicated by mitochondrial
cules may both detoxify nanomaterials, and promote activity in converting a formazan type of dye from its leu-
uptake into cells that can reduce clearance and lead to koform to an active dye. In addition, DNA content, indi-
chronic, degenerative changes. cating cell number was measured (Brunner et al., 2006).
Solubility can be an important determinant of biologi- Other than the positive asbestos control, none had .20%
cal response. Solubility is a function of chemical activity, of the particles larger than 200 nm. Specific surface area
specific surface area, radius and curvature, agglomeration was also higher than the asbestos positive control
2
2
and specific chemicals that are adsorbed to the ENM (90 190 m /g vs the 8.5 m /g of the asbestos). Mass
(Borm et al., 2006). Larger, more densely aggregated par- median sizes were 20 50 nm and surface area median
ticles will dissolve more slowly. Adsorbed organic sizes were 6 21 nm, although they differed in terms of