Analyzing the Biological Entity of Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 58

4.4.1 Physiological Considerations .............................................................. 85
4.4.2 Available Models ................................................................................ 86
4.4.3 Conclusions and Considerations for Future Studies ........................... 87
4.5 Summary and Conclusion ............................................................................... 88
Glossary ................................................................................................................... 90
References ................................................................................................................ 90
4.1 INTRODUCTION
4.1.1 W hy i s i t i mPortant to C haraCterize n anomaterials I n S Itu ?
The complete and careful analysis of the test item is a well-accepted paradigm, a
prerequisite for any type of toxicological testing. This also applies for nanotoxico-
logical studies. Of course, the issue of how to characterize particles appropriately is
not completely new. Particle science has dealt with all aspects of particle character-
ization for many years, and nanotoxicology can—and should—use this expertise.
As summarized by Powers et al. (2007), this starts with sampling, as the analyzed
fraction of the sample needs to be a representative of the material under study. This
becomes especially important when the particles have a broad size distribution. For
the same reason, many particles (e.g., several thousands) need to be analyzed to
obtain a reliable statistics, and the sample should be analyzed as close as possible to
the relevant conditions (e.g., in biological environment), and just before the experi-
ment (Powers 2005). However, in many of the older studies particle characterization
was only conducted on a very minimalistic level. Therefore, questions were raised
about the meaning of such studies in the absence of adequate material characteriza-
tion (Warheit 2008). Nowadays there is a large consensus that a complete and exten-
sive characterization of the nanoparticles is an essential starting point for any type of
study. This has been intensively discussed in many publications (Jiang, Oberdörster,
and Biswas 2008; Murdock et al. 2008) and summarized in several review articles
(Sayes and Warheit 2009; Powers 2005; Powers et al. 2007), as well as guidance doc-
uments (OECD 2012). Most of these documents and articles give an excellent over-
view on which characterization data are needed and which techniques are suitable to
obtain them. This refers to different physical-chemical properties, such as chemical
composition, size, size distribution, shape, surface, or surface charge. But as pointed
out by Warheit currently “this recommendation becomes a 'laundry list' of physico-
chemical characteristics and does not have adequate prioritization” (Warheit 2008).
Additionally, many studies do not pay attention to nanomaterial characterization
under the conditions of use, for example, in a biological context. Instead, the nano-
materials are characterized as they have been received, in most of the cases either
as a powder or as an aqueous dispersion. This is referred to as characterization of
materials as produced or as synthesized (also refer to Chapter 1). However, nanoma-
terials may change their characteristics over their entire lifecycle. A nanomaterial
that is shipped as a dry powder needs to be dispersed before any use. As soon as the
nanoparticles get into contact with any type of biological matrix they will interact
with biomolecules of the matrix and change their properties with respect to size
(e.g., agglomeration), adsorption of biomolecules onto the surface (i.e., formation