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

NanoSafetyCluster - Compendium 2012
1 Summary
Engineered Nanoparticles (ENP) are increasingly produced for
use in a wide range of industrial and consumer products. Yet it is
known that exposure to some types of particles can cause
severe health effects. Therefore it is essential to ascertain
whether exposure to ENP can lead to possible health risks for
workers and consumers. We have formed a consortium of wellknown
scientists from European Universities and Research
Institutes, with over 100 publications in the field of
Nanotoxicology. Our aim is to develop an approach for the Risk
Assessment of ENP (ENPRA). Our objectives are:
• to obtain a bank of commercial ENP with contrasting
physico-chemical characteristics and measure them;
• to investigate the toxic effects of ENP on 5
(pulmonary, hepatic, renal, cardiovascular and
developmental) target systems and 5 endpoints
(oxidative stress, inflammation; immuno-toxicity;
fibrogenecity; genotoxicity) using in vitro
•
animal/human models;
to validate the in vitro findings with a small set of
carefully chosen in vivo animal experiments;
• to construct mathematical models to extrapolate the
exposure-dose-response relationship from in vitro to in
vivo and to humans;
• to use QSAR like models to identify the key ENP
characteristics driving the adverse effects;
• to implement a risk assessment of ENP using the
Weight-of-Evidence approach;
• to disseminate our findings to potential stakeholders.
To harmonize the research activities between our EU
group and the US, we have established links with
scientists from US Universities (Duke, Rochester) and
Government Agencies (NIH/NIEHS, NIOSH and EPA)
with on-going research in Nanotoxicology.
Our objectives here are
• to share information and agree on experimental
protocols;
• to avoid duplication of work.
• to further validate the findings of this proposed study.
2 Concept
Nanotechnology is one of the key industries in Europe1. The
estimated economic impact of nanoparticles in industrial,
consumer, and medical products will be US$ 292 billion by 2010
and US $1 trillion by 2015. The prosperity of our continent
depends on the safe and sustainable development of this
emerging technology 2. Every new technology brings with it
new risks and for nanotechnology, the potential health risks to
workers and consumers are paramount. They can arise from
exposure to nanomaterials either at work or through consumer
products. These risks, if not assessed and managed properly,
can prevent economic growth and deprive us of a much needed
competitive edge, but more importantly could have grave
potential consequences for human and environmental health
2;3. Being aware of the health issues concerning engineered
nanomaterials, in 2006, some of the ENPRA partners have
written an article, published in Nature4, outlining the grand
challenges for the safe handling of nanotechnology. It is clear
that the production of safe nanomaterials is essential to
establish and sustain the confidence of end users. This
confidence is the ultimate guarantor for nanotechnology
growth. It is therefore essential to develop an effective
approach for improving the assessment and management of
potential health risks from exposure to engineered
nanoparticles (ENP)5. This is the overall aim of ENPRA.
2.1 Aim and Objectives
The principal aim of ENPRA is to develop and implement a novel
integrated approach for ENP Risk Assessment (ENPRA). This
approach is based on the Exposure-Dose-Response Paradigm
for ENP (Figure 1). This paradigm states that exposure to ENP of
different physico-chemical characteristics via inhalation,
ingestion or dermal exposure is likely to lead to their
distribution, beyond the portal-of-entry organ to other body
systems. The cumulative dose in a target organ will eventually
lead to an adverse response in a dose-response manner. Our
approach will adapt the traditional Risk Assessment approach to
ENP and will cover: Hazard Identification; Dose-Response
Assessment; Exposure Assessment and Risk Assessment,
Management.
The specific objectives of ENPRA are: (i) for Hazard
Identification: To characterize a panel of commercially available
ENP carefully chosen to address the relevant hazards,
properties and potential mechanisms1; (ii) for Dose-response
Assessment: To assess the hazards of these ENP by means of in
vitro toxicology tests based on five body systems: (1)
pulmonary; (2) hepatic; (3) renal; (4) cardio-vascular and (5)
developmental, and five endpoints: (a) oxidative stress; (b)
inflammation and immune-responses; (c) genotoxicity; (d)
fibrogenecity and (e) developmental toxicity; (iii) To verify the in
1
The ENP selected represent a subset from a panel of ENP chosen as
reference materials for testing in a UK government (DEFRA) funded
project and is very likely to be fed into the OECD plan for reference
materials testing. The samples were chosen with contrasting properties on
size/surface area (TiO2), charge (silica), shape (MWCNT), surface chemistry
(silver, iron).
16 Compendium of Projects in the European NanoSafety Cluster