Particle and Fibre Toxicology - Nanowerk

Particle and Fibre Toxicology 2005, 2:8
http://www.particleandfibretoxicology.com/content/2/1/8
susceptible to errors where the sampled aerosol contains
volatile components. On-line photometric mass
concentration methods are generally good for monitoring
the temporal stability of aerosol and providing a real-time
indication of mass exposure, although they are relatively
insensitive to particles smaller than approximately 0.5 µm
in diameter [86]. However, in general more appropriate
methods should be used for providing real-time measurements
of number and surface-area exposure [85,87-89].
Aerosol size distribution measurements enable reasonably
good calculation of exposure against all three physical
metrics, if parameters such as particle shape and density
are known. Off-line size distribution measurement methods
such as Transmission Electron Microscopy (TEM)
analysis offer detailed information on this distribution
but are extremely time consuming, and frequently limited
by the collection techniques and, in the case of TEM analysis,
inference of 3-dimensional structure from 2-dimensional
images. On-line size measurement techniques such
as Differential Mobility Analysis [90] are capable of measuring
aerosol size distribution with a time resolution of
tens of seconds. Aerosol number concentration between
given particle diameters is easily derived from aerosol size
distribution measurements, although interpretation of
such data in terms of mass or surface-area dose requires
additional information on particle characteristics such as
shape and density. It is recommended that for each nanoparticle
type, size distribution measurement techniques
be validated against TEM analysis.
Off-line surface area characterization is possible using
isothermal gas-adsorption, although techniques suited to
filter samples need to be employed. There is also some
possibility that the surface area of the collected material
will differ from that of the airborne material due to compaction
and surface occlusion. However, the extent to
which this may occur is not well understood. Published
studies have shown a good correlation between off-line
surface area measurement and biological response [91],
suggesting that errors associated with collection and subsequent
analysis can be small. This holds particularly for
insoluble particles; ideally surface area measurements
would be required on the insoluble core of a nanomaterial
after its water-and/or lipid soluble compounds have
been dissolved from the particle surface. Aerosol diffusion
charging has been shown to provide a measure of surface
area on-line where the charging rate is low [89], and a
small number of aerosol diffusion chargers are commercially
available. These devices have been shown to measure
aerosol surface area well for particles smaller than 100
nm in diameter [87]. At larger diameters, measured surface
area progressively underestimates aerosol surface
area. In particular, the surface area of porous particle
structures as well as that of highly aggregated particles will
Table 1: Recommendations for measuring exposure during
inhalation studies
Metric
Mass – off-line
Mass – on-line
Size distribution – off line
Size distribution – on line
Surface area – off line
Surface area – on line
Number – off line
Number – on line
Measurement
Recommendation
E (coupled with on-line)
E
E
E/D
O
O
N
E
E: These measurements are considered to be essential.
D: These measurements are considered to provide valuable
information, but are not recommended as essential due to constraints
associated with complexity, cost and availability.
O: These measurements are considered to provide valuable but nonessential
exposure information.
N: These measurements are not considered to be of significant value
to inhalation studies.
generally not be determined. Data have been published
on a particular aerosol diffusion charger indicating that it
provides a measure of aerosol surface area dose in the
lungs, as opposed to aerosol surface area exposure [92].
While on-line aerosol surface area measurements are
desirable during inhalation exposure studies, uncertainties
associated with current techniques suggest caution
when interpreting such measurements.
Number concentration may be measured on-line with
relative ease using instruments such as Condensation Particle
Counters [88]. Although it is not clear how biologically
relevant number concentration is as a dose metric,
the ease with which such measurements are made and
their value in tracking temporal changes in exposure lead
to their being recommended as essential in inhalation
studies.
Table 1 summarizes recommendations for measuring
exposure during inhalation studies.
4.1.5 Characterization Prioritization
In developing recommendations on material characterizations
for nanomaterial toxicity screening studies, three
specific factors have been taken into consideration: the
context within which a material is being evaluated, the
importance of measuring a specific parameter within that
context, and the feasibility of measuring the parameter
within a specific context. Recommendations on off-line
material characterizations for nanomaterial toxicity
screening studies are presented in Table 2.
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