Concern-Driven Safety Assessment of Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 367

2011). Bovine serum albumin and fetal bovine serum have been suggested as dis-
persing agents for biological studies in mammalian tissue culture media (Thomas
et al. 2011). However, dispersing agents containing lipids and lipophilic surfactant
proteins reflecting lung lining fluids have also been recommended because they
more closely mimic an in vivo-like situation in in vitro test systems (Sager et al.
2007; Gasser et al. 2012; Schleh et al. 2013). Over the past few years, multiple dis-
persion protocols have been used, and an extensive list of parameters and assays
for in situ NM characterization have been proposed (Hassellov et al. 2008; Schulze
et al. 2008; Card and Magnuson 2010; SCENIHR 2009; OECD 2010; Wohlleben
2012) and are discussed in Chapter 4. Further development of tools and exposure
scenario libraries is required to estimate the physicochemical characteristics of a
NM at various life stages, tools to identify and rank the most relevant concerns, and
guidance for testing that takes the relevant physicochemical characteristics related
to the concern into account.
Combining the outcome of the exposure assessment and the physicochemical
characterization (material properties), taking into account all available information
also from the material and other read-across approaches and physiologically based
pharmacokinetic modeling, will allow determining NMs of “potential concern”
(Figure 16.3, step 3). How this information should be combined needs further con-
sideration. Many NMs will not raise specific concerns, but will, for example, read-
ily dissolve. Other NMs are likely to possess properties raising concerns for toxic
effects. These concerns may be general or restricted to specific uses and exposures
(refinement of concerns, identification of “actual, relevant concerns”; Figure 16.3,
step 4). For instance, NMs solely used in nonspray cosmetic sunscreen lotions may
be of low concern for inhalation toxicity for consumers.
In this context, it is crucial to define which type of concern is being addressed in
the course of the risk assessment: concerns can be exposure-driven (e.g., low expo-
sure vs. high exposure), hazard-driven (e.g., based on known, potentially adverse
effects), biokinetic-driven (e.g., biopersistent, transport across placenta, or blood-
brain barrier), or societal (e.g., the acceptance or nonacceptance of a risk level).
At an early stage, physicochemical characteristics might be considered to estimate
exposure, biokinetic fate, and/or hazard potential of a NM. At some point, an open
discussion is required to determine which level of certainty on the potential risks of
a given NM in a specific application the society considers acceptable. Such delibera-
tions, however, exceed the scope of the present essay.
The outcome of the four steps of identification of relevant concerns (Figure 16.3,
corresponding to Tier 1 of the IATA presented in Figure 16.4) should be used to
define the crucial human health end points to be tested in focused studies. It should
further aid to determine the appropriate test design of these studies, including the
relevant route of exposure, and all of the criteria used to identify concerns can also
be considered for the grouping of NMs. If one or more concerns are identified, fur-
ther data are necessary: In the case of a new NM, the next step implies generating
additional data to perform Tier 2. In the case of an existing NM, appropriate tests
might be chosen from Tiers 2 or 3 depending on the amount of information that is
already available and depending on the information that is expected to be most effec-
tive and efficient for risk assessment.