Timing, hosts and locations of (grouped) events of NanoImpactNet

NanoSafetyCluster - Compendium 2012
ultimately in the Risk Management of ENM. In the text below, the
specific beyond the state-of-the-art research in MARINA for each
important Themes are described in more detail.
Materials
We will establish a panel of representative ENM of high volume
production and of high economic importance (e.g. TiO2 – in
different size, shape and surface charge, SiO2, Ceria Oxide, ZnO,
nanoAg, Multi-Wall Carbon Nanotubes (MWCNT) – in different
lengths) as Reference Nanomaterials (RNM) for use in MARINA.
Commercially relevant, fully characterised and quality-controlled
ENM will be sourced from both industry partners (via NIA) and the
JRC’s repository for reference nanomaterials, which is already subsampling
and distributing several commercially relevant ENM for
other nanotoxicology projects, including the OECD Sponsorship
programme. These RNM will be characterised, assessed for
homogeneity, stability and described shelf-life according to the
OECD WPMN SG3 67 endpoints and criteria. We will use these RNM
to validate the metrology methods for measuring key physicochemical
ENM characteristics, which are suggested to drive the
adverse effects. Important inputs to these activities will come from
the nanometrology community (e.g. FP7 co-Nanomet and ISO
TC229). We will harmonise and standardise these methods for the
qualification/certification of these reference materials according to
ISO Guide 30-35 and OECD Guide 34 as well as ongoing work at the
OECD Sponsorship Programme for both risk assessment and
nanometrology purposes. To date, there is no consistent method
for labelling ENM, although knowing the target organ/cell dose is
essential in understanding the nature of the dose-response
relationship. In MARINA we will develop and validate methods for
labelling ENM for studying the bio-distribution of ENM in body
tissues. We will also develop and validate methods for
characterising ENM in biological matrices and environmental
samples from air/soil/sediment/water for field detection. MARINA
will also characterise ENM released from products and aged under
environmental conditions, as these are the ENM that the
organisms are exposed to. Comparisons to the pristine ENM will be
made.
Exposure
i. For Occupational and Consumer Exposure, In
collaboration with the relevant industries, we will identify the
relevant current and future occupational exposure scenarios and
review available occupational/consumer exposure information and
conduct exposure surveys to complement the occupational and
consumer exposure data. We will review and revise models for
predicting exposure to ENM in the workplace and from consumer
products and implement these in an advanced control banding
tool. We will also develop and implement a strategy for
occupational and consumer exposure monitoring including the
charaterisation of workplace and consumer product samples;
these strategies will be verified through industrial case studies,
using both real-case exposure scenarios.
ii. For Environmental Exposure, we will review available
environmental, identify and formulate the current and future
environmental exposure scenarios, validated by monitoring. We
will develop adapt and validated experimental guidelines for the
fate and behaviour assessment of ENM in soil, sediment and water.
This will be based on analysis ENM binding to and partitioning from
natural components, including importance of agglomeration;
besides distribution, availability and stability of ENM under
standardised and real environmental conditions will be assessed.
The data generated will allow parameterisation of the fate
processes scientifically and permit the implementation of
regulatory exposure assessment frameworks.
iii. For both spillage and explosion, critical parameters
controlling risk, like concentration of agglomerates, the explosion
severity, the minimal ignition energy and many others, will be
identified experimentally, new reference evaluation methods of
such parameters will be developed and quantified. using the
unique expertise in pulse/intermittent exposure in our consortium.
Moreover, for accidental release models, industry case-studies will
also be used in support of the development of experimental
models for massive accidental exposure from explosion.
70 Compendium of Projects in the European NanoSafety Cluster
Hazard
i. For Toxicology, we will develop new in vitro toxicology
test methods on the following target systems: the immune, central
nervous, cardio-vascular, pulmonary, hepatic, renal, reproductive,
developmental and dermal systems. The adverse endpoints are
target specific as well as oxidative stress, inflammation,
genotoxicity, fibrosis. We will also investigate the ability of ENM to
translocate across biological barriers such as the blood-brain,
blood-air, endothelial and placental barriers and determine the
ENM physico-chemical properties which facilitate this dynamics.
Moreover, the interaction between ENM surface physico-chemical
characteristics and body proteins and lipids is fundamental in how
cells react to the presence of foreign entities. Thus, we will
investigate this phenomenon in relation to the potential toxicity
and translocability of ENM Most importantly, we will implement
animal experiments dose-response and bio-distribution ADME
models of healthy, pregnant and susceptible (to cardio-vascular
problems) individuals exposed through repeated dosing to ENM
via inhalation, ingestion, iv injection and dermal routes.
ii. For Eco-Toxicology, we will adapt and if develop in vitro
and in vivo tests for soil, sediment and aquatic toxicity including
secondary poisoning. Current test will be modified or if needed
developed then standardised and validated for use with ENM. Key
effect endpoints and dosimetry parameters directly specific to
ENM will be identified, this will be done across all media benefiting
on the size of the consortium. Data will be complemented by
mechanistic information (see iii).
iii. For both Toxicology and Eco-Toxicology, we will develop
methods for toxicological profiling using toxicogenomics,
proteomics and metabolomics including some unique arrays that
are being adapted for ENM available to the consortium and
therefore identifying ENM specific Modes of Actions (MoA). We
will adapt existing in vitro tests nominated by current FP projects,
and harmonise toxicology and eco-toxicology endpoints into one
unified framework for hazard assessment. The tests will be
validated by reliability assessment and inter-laboratory round robin
comparative tests and the selected ones will be implemented in
High-Throughput Systems (HTS). Ultimately, we will integrate the
validated tests into an intelligent Testing Strategy (iTS) and