Concern-Driven Safety Assessment of Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 356

16.1 INTRODUCTION
Although more and more nanomaterials (NMs) continue to be produced with almost
infinite variations in size, shape, structure, and surface modifications (Lövestam
et al. 2010), a generally applicable paradigm for NM hazard identification and risk
assessment is not yet available. Not only their physicochemical characteristics may
have an impact on the extent and type of biological effects they induce, additionally,
unlike conventional chemicals, exposure to NMs is not to a distinct type of molecule,
but to a population of primary particles, aggregates, and agglomerates of various
sizes and different surface coatings that may change in characteristics with time
(compare Chapter 4 and Section III). These characteristics can influence exposure
and kinetic behavior, as well as the type of effect of the NM. This complicates clas-
sical risk assessment approaches and multiplies the need for efficient and effective
hazard testing and exposure assessment.
In recognition of this multitude of potential variations for NMs, the Scientiic
Committee on Emerging and Newly Identified Health Risks , an advisory body to the
European Commission, has recommended for the time being a case-by-case approach
for NM hazard and risk assessment (SCENIHR 2009). Traditional toxicity testing
calls for a substantive number of tests that are mostly restricted to the mere observa-
tion of apical (clinical or histopathological) effects (Combes et al. 2003; OECD 2012a).
If based upon such traditional toxicological testing methods, one-by-one assessment
of all potential hazards of NMs (just as the hazards of chemical substances as such)
would result in the use of very large numbers of laboratory animals and high associ-
ated cost. This is even more true if all potential hazards associated with changes in
physicochemical characteristics during a NM's lifecycle are taken into account. Yet,
safety of NMs should be demonstrated before administration to the market.
This, however, would contravene the 3Rs principle to replace, reduce, and refine
animal testing (Russell and Burch 1959) that has been implemented in the European
Union (EU) Directive 2010/63/EU on the protection of animals used for scientific
purposes (Anon 2010). Also the EU Chemicals Regulation No. 1907/2006 (REACH,
Registration, Evaluation, Authorisation of Chemicals; Anon 2006) prescribes that
animal testing should only be undertaken as a last resort.
As a consequence, there is an urgent need for new integrated approaches for the
integrated testing and assessment (IATA) of NMs (George et al. 2011; Kuempel et al.
2012). An efficient and effective testing strategy should provide guidance on how to
obtain the information actually relevant for risk assessment of a specific NM and its
application, and include options for “non-testing” methodologies, such as “read-across”
and “weight-of-evidence” (Information Box 16.1), and nonanimal test methods as part
of tiered testing strategies (Combes et al. 2003; IHCP2005). The application of such
nontesting methods has been included in the REACH legislation. An efficient testing
strategy should exploit and combine all available information on exposure and toxicity
to identify relevant concerns and to determine those data that best address these con-
cerns (Combes and Balls 2005; van Leeuwen et al. 2007; OECD 2012a). Today there
is, however, very little experience with grouping and read-across for NMs.
Integrated approaches for the testing and assessment of the safe production and
use of chemicals have also become the pillar of the United States National Research