Concern-Driven Safety Assessment of Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 359

that. Furthermore, they take into account the proceedings of international initia-
tives addressing NM hazard and risk assessment, that is, the OECD Working Party
on Manufactured Nanomaterials (WPMN * ) and the International Standardisation
Organisation Technical Committee 229. † WPMN steering groups have addressed
innovative risk assessment approaches and have compiled a list of in vitro methods
that might be used for NM human hazard identification. Additionally, the WPMN
has proposed a new short-term inhalation study for NM testing that provides an indi-
cation of the hazard (potential and potency for local [airway] effects and potential
also for systemic effects) and includes some kinetic parameters to investigate if the
NMs translocate from the respiratory tissues and thus if systemic effects should be
investigated (Ma-Hock et al. 2009; OECD 2011; Klein et al. 2012).
Information on the source-to-adverse-outcome pathway can facilitate safety
assessment and grouping of a NM. These pathways depend, amongst others, on the
physicochemical characteristics of the NM, which may change at the various lifecycle
stages (compare chapter in Section III). The different physicochemical characteristics
will affect the exposure, biokinetics, and effects of a NM. Hence, these parameters
can and should be considered for the safety assessment and grouping of NMs.
16.2 NANOMATERIAL TOXICITY PATHWAYS AND
ADVERSE OUTCOME PATHWAYS
Aiming for an understanding of the mechanisms of toxicity that can be induced by a
substance is a prerequisite to recognizing relevant concerns and selecting appropri-
ate toxicity tests. Early biological effects of NMs (compare chapters in Section II)
may be related to the particles themselves and their coatings (particle effects); ions
or molecules released from the particles (chemical effects); and molecules formed by
the catalytic surface of the particles (Landsiedel et al. 2010).
Different types of NMs can induce different early biological effects (Nel et al.
2013b): Titanium dioxide, copper oxide, and cobalt oxide NMs, for instance, have been
observed to induce the generation of reactive oxygen species (ROS) and to increase
redox activities. Metal and metal oxide NMs, such as zinc oxide and silver, can exert
toxic effects by dissolution and the shedding of toxic ions. Activation of proinflamma-
tory reactions has been reported for several NMs and persistent long-aspect ratio (fiber-
like) NMs, such as carbon nanotubes (CNT), can cause sustained inflammation. Further
NMs, including SiO 2 nanoparticles and Ag plates, might induce membrane damage and
lysis; whereas the effects of, for example, cationic polystyrene NMs are likely related
to cationic toxicity leading to lysosomal rupture and mitochondrial damage (Xia et al.
2008; Meng et al. 2009; Damoiseaux et al. 2011; Zhang et al. 2012; Nel et al. 2013b).
Obviously, one NM may be able to induce more than one early biological effect.
Depending on their toxicity pathway, NMs have different modes of action (MOA)
and can elicit different adverse outcome pathways (AOP) (Information Box 16.2):
The proinflammatory effects caused by CNT, for instance, can result in pulmonary
fibrosis, which, when progressive, might lead to severe dysfunction of the respiratory
* See: http://www.oecd.org/env/ehs/nanosafety/ note: all websites were accessed in June 2013.
† See: http://www.iso.org/iso/iso_technical_committee?commid=381983.