Concern-Driven Safety Assessment of Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 362

in vitro doses and cellular uptake of NMs should be considered. Most NM particles
>20 nm may, for example, not be able to enter Salmonella used for the Ames test.
The uptake, tissue distribution, and clearance of NMs may be different from dis-
solved molecules or larger particles (Landsiedel et al. 2012a), and thus needs further
attention, especially as this behavior depends on physicochemical characteristics
that may change during the life stage of the NM. This also implies that physico-
chemical characterization should be performed not only for the pristine material but
also in situ at critical lifecycle stages.

16.3 GROUPING OF NM

16.3.1 C onCePt of g rouPing
The classical grouping concept implies considering closely related materials as a
group, or category, rather than as individual materials. In a category approach to
hazard assessment, not every material needs to be tested for every single end point.
Instead, the overall data for a given category allow estimating the hazard for the
untested end points (OECD 2007). Use of information from structurally related
materials to predict the end point information for another material is called read-
across (Anon 2006; Information Box 16.1). In the registration dossiers submitted
during the first REACH registration phase, read-across was frequently applied to
avoid the generation of new data (Spielmann et al. 2011). However, according to the
European Chemicals Agency (ECHA), oftentimes, it was not sufficiently detailed or
adequately justified (ECHA 2012b, 2012c).
Compared to the grouping of conventional chemicals, the grouping of NMs is an
even more complex challenge. So far, no single physical or chemical material prop-
erty—be it surface, volume, or ROS generation—perfectly correlates with the observed
biological effects for various types of NMs (Landsiedel et al. 2012b; Zuin et al. 2011;
Nel et al. 2013b). More than a dozen physicochemical properties of NMs have been
identified that could potentially contribute to hazardous interactions, including chemi-
cal composition, size, shape, aspect ratio, surface charge, redox activity, dissolution,
crystallinity, surface coatings, and the state of agglomeration or dispersion (Thomas
et al. 2011). Some of these characteristics influence also biokinetic processes and thus
the fraction of a NM that reaches the target site, whereas potentially other—or another
set of—material properties influence the biological effects. This may confound the
correlation between one single material property and an apical effect.
NM complexity requires developing more comprehensive grouping of NMs for risk
assessment. At the same time it offers the opportunity to include more information:
NM grouping should not be restricted to the determination of nanostructure-activity
relationships, but should take into account the entire source-to-adverse-outcome path-
way, including changing of physicochemical characteristics of a NM.
Therefore, the pillars of NM grouping should be

• The lifecycle of a NM, including its production, use, and release

• The physicochemical characteristics of a NM, which can be different in

different lifecycle stages (e.g., release and external exposure of organisms)