High Aspect Ratio Nanomaterials - Aerosols: Measurement, Dosimetry, and Health Effects - page 236

Exposure

Dose

Deposition

Short fibers/
particles

Long fibers

Dimension

Normal effective
clearance

Non-biopersistent Biopersistent

Durability

Failed clearance
incomplete phagocytosis,
cell activation

Dissolution

Pathogenic
effects

Cleared Breakage Dissolves

FIGURE 10.3 Role of the 3Ds in iber pathogenicity. (Adapted from Donaldson, K. et al., Toxicol. Sci ., 92(1),

5, 2006.)

The iber pathogenicity paradigm (FPP) depends on three critical features that are required for
a ibrous particle to present a iber-type health hazard. These attributes consist of, most crucially,
exposure to the particle in question ( dose ), the role of aspect ratio and length ( dimension ), and the
persistence of a particle in the biological environment and its resistance to breakage and dissolution
( durability ) (Donaldson and Tran, 2004). These components of dose, dimension, and durability, or
the 3 Ds provide the cornerstone of the FPP as summarized in Figure 10.3.

10.3.2.1 Dose
Exposure to an agent—particle, chemical, or biological—is required to elicit a response. As
the absence of exposure leads to an absence of response, exposure or dose is arguably the most
important of the 3Ds when deining the health risk of ibers. It is necessary to irst consider
how exposure may lead to dose. External exposure is simply the presence of particles or some
other form of exogenous material found in the environment external to the body (i.e., a source ),
however the presence of a substance in this external environment does not necessarily mean that
it shall gain entry into the body. For a substance present as a source to gain entry to the body,
a pathway is required, which can lead to the presentation of an internal dose that may go on to
cause any effect. If a particle or HARN is respirable, it may gain access to the lungs leading to an
internal dose. This does not necessarily mean that there will be a subsequent biological effect, as
the dose may still be too low or the substance may not be toxic and/or cleared rapidly (removal
of dose), or deposit in a region not leading to toxicity.
In the case of studies relating the incidence of disease, the establishment of dose is usually
based on quantitative or semiquantitative estimates of external exposure from occupational/
industrial hygiene assessments using air monitoring. This only allows an accurate measurement
of the external exposure and generally only gives a proxy measure of the internal dose, which
is what would lead to a pathological effect. While actual internal measurements of dose, zones
of deposition, and clearance rates are dificult in humans, mathematical models based on lung
structure and airlow have aided signiicantly in bridging the gap between exposure and internal