Concern-Driven Safety Assessment of Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 370

the extent of their transportation across these barriers (in return providing indica-
tions for the choice of subsequent specific end points, such as reproduction toxicity,
cardiotoxicity, or neurotoxicity). To date, little is known about the parameters that
influence NM transportation (Oberdörster 2009; Landsiedel et al. 2012a). This infor-
mation is, however, highly valuable for the identification of concerns and application
of the grouping concept.
NMs generally tend to disappear rapidly from the blood by being taken up into
tissues, mainly those containing phagocytic cells. Once filtered from the blood by
macrophages, NMs are eliminated from these cells, and the body, only to a limited
extent (Lankveld et al. 2010; Dan et al. 2012).
Intentional or unintentional modifications of the NM surface may have an
impact on the translocation across barriers, on the tissue distribution of NMs,
on the rate in which distribution occurs, and on their effects to the organism
(Nel et al. 2009; Landsiedel et al. 2012a; Lundqvist et al. 2011; Liu et al. 2012).
A “corona” of biological molecules will form around the NMs when they enter the
body or even before, for example, when they are added to food products (Nel et al.
2009; Lundqvist et al. 2011; Johnston et al. 2012). This corona is most likely com-
posed not only of proteins but also of lipids and carbohydrates, see Chapter 4.3
and Gasser et al. (2010). It is dynamic, because its types of molecules may change
with time. A number of proteomics methods to identify the nature, composition,
and dynamics of the biomolecules associated with NMs have been developed (Lai
et al. 2012).
Slow elimination and persistence suggest potential bioaccumulation. Similar to
conventional persistent, lipophilic chemicals that are resistant to biological degra-
dation, NMs may have the potential to accumulate in humans (or the environment)
when the frequency and magnitude of the exposure lead to an uptake exceeding the
elimination in the body. Information on the potential of NMs to bioaccumulate is a
criterion for higher-tier hazard and risk assessment that is more focused on effects
at chronic exposure.
16.4.4 s PeCifiC t esting B ased uPon the o utCome of t iers 1 and 2
The outcome of Tier 2 tests, combined with the information obtained in Tier 1,
will allow identifying the need for additional information and appropriate toxicity
domain(s) to be addressed in Tier 3 (Figure 16.4). So far, very limited data on long-
term NM effects are available. Considering the relevance of the inhalational route
of exposure, long-term inhalation studies should be performed with selected NMs,
also allowing recognition of pathways by which NMs could cause lung tumors (e.g.,
inflammation, overload, and genotoxicity). As soon as such general principles and
how these pathways can be indicated by simple tests are understood, less demanding
tests can be applied in the toxicity testing strategies (e.g., appropriate in vitro assays
and short-term inhalation tests). The data and tools applied at Tier 3 should allow a
final conclusion on the acceptability of the risk, which infers the decision making on
the risk management measures to be taken.
In summary, IATA aims at identifying and addressing concerns and thus reduc-
ing the uncertainty about potential risks by applying increasingly specific tools from