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

NanoSafetyCluster - Compendium 2012
properties of nanomaterials (NMs) and their potentially
unpredictable behaviour, and thus models need to acquire a level
of sophistication to accommodate that. Both statistical and
mechanistic models are needed. Statistical models are necessary
when mechanistic understanding is lacking and to capture
uncertainties in relationships between nanoparticle properties and
their behaviour. However, mechanistic models are more
appropriate for extrapolating beyond existing data sets and
exploring different scenarios.
3 What is ModNanoTox
ModNanoTox is a small project, designed to develop a number of
well-documented integrated and technically advanced models
describing the behaviour of engineered nanoparticles in an
environmental or biological context to comprehensively address
the following key hypotheses:
1. Toxicity of nanoparticles is the result of physicochemical
properties and this has been documented reliably in
completed/ongoing studies. Properties found to be relevant
include size, surface area, structure and composition (WP1, 2)
2. Nanoparticle reactivity can be modelled computationally and can
be linked to toxicity (WP1).
3. Toxic responses from cell culture studies and whole organisms
can be correlated and rationalised and can be translated into tools
useful for model development (WP2).
4. Bioaccumulation into cells or whole organisms can be
characterized and modelled using biodynamic principles (i.e. by
characterizing uptake rate constants from food and water as well
as loss rate constants) (WP3).
5. Toxic responses from cell culture studies and whole organisms
can be modelled reliably by QSAR type approaches (WP4).
6. Exposure concentrations can be assessed reliably and
incorporated in appropriate models (WP5).
7. Mechanistic effect models can be developed by extrapolation
from ecological and (eco)toxicological observations and can be
built into risk assessment models (WP6).
4 Organisation of ModNanoTox
ModNanoTox consists of six RTD and one management
workpackage. The workpackages and their interdependence are
shown schematically in Figure 1. The specific objectives of each
workpackage are as follows:
WP1: Physicochemical properties assessment
1) To identify and select suitable physicochemical properties (size,
shape, phase, concentration, composition, surface modification,
method of synthesis) so that groups of structurally similar particles
can be identified for toxicity models.
2) To carry out atomistic simulations of surface reactivity of a
reference set of particles (Ag NPs) to support this selection.
3) To develop mechanistic understanding of nanoparticle reactivity
based on molecular models.
Public outreach Scientific
Legislators, industry publications
Figure 1. Workpackage structure of ModNanoTox.
WP2: Data evaluation
1) To characterise and classify existing toxicity data (data mining),
including evaluation of datasets from completed and on-going
projects, in order to prioritise data for modelling in other
workpackages.
2) To evaluate differences in parameters due to contributing
factors such as synthesis, storage, and through to testing.
3) To recognise data quality limitations.
4) To evaluate characterisation and classification techniques.
WP3: Bioaccumulation models
1) To model toxicity at the individual organism level using
bioaccumulation based toxicokinetic- toxicodynamic models.
2) To generate models, based on individual organisms, capable of
incorporating experimental nanoparticle uptake and toxicity data
and identify links to the mechanism of toxic action.
WP4: QSAR models
ModNanoTox: graphical presentation of work packages
Physicochemical property assessment
WP1
Bioaccummulation models
WP3
1) To model toxicity at individual organism level using QSAR
models, based on data mining and machine learning algorithms.
2) To adapt existing models and generate new models capable of
linking toxicity to nanoparticle properties.
WP5: Exposure concentration models
QSAR models
WP4
Exposure concentration models
WP5
Data
evaluation
WP2
1) To evaluate models to estimate environmental exposure,
including the REACH procedures.
2) To parameterize existing models for nanoparticles by extracting
data from the literature and by collecting results from ongoing FP7
projects.
76 Compendium of Projects in the European NanoSafety Cluster
Consortium Management
WP7
Population models and risk assessment
WP6
US EPA projects