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

NanoSafetyCluster - Compendium 2012
WP4: Interactions with in vivo models. In vivo testing is being
performed on at least eight different species to allow the
construction of species sensitivity distributions for the selected
nanoparticles. This also includes three standard toxicity species of
which the acute and chronic toxicity is well documented and
characterised for a variety of toxicants (e.g. Chlorella, Daphnia, and
Danio). The in vivo experiments address three main issues: namely
bioavailability, accumulation and toxicity. A series of chronic
experiments are being performed in which effects on growth and
reproduction are being determined. This work is led by Antwerp
with an input from Anton Dohrn. Antwerp is one of the world
leaders in molecular, cellular and whole-organism toxicology, and
both experimental and predictive modelling. In the last year
studies have concentrated on looking at the chronic toxicity and
internalisation routes of nanoparticles. In a chronic exposure
scenario over 21 days, the ZnO nanodispersion (Alpha Aesar
NanoTek) is toxic to Daphnia magna at low concentrations (around
0.02 mg Zn/L), whereby especially the reproduction was affected.
As it has already been observed in studies carried out in WP3,
toxicity of the ZnO nanodispersion cannot be solely due to the Zn
or Zn 2+ toxicity (see Figure 8).
Figure 8: Chronic toxicity of ZnO nanodispersion on the
reproduction of Daphnia magna (mean ± SD) after 21 days of
exposure. Number of juveniles per adult Daphnia; one-way ANOVA
with Dunnet’s post test, significant differences p < 0.001-0.01 (left)
and sigmoidal dose-response curve on the inhibition of
reproduction (right).
Results also showed the uptake and internalisation of the ZnO
nanoparticles in Ciona intestinalis (see Figure 9). However, under
the tested conditions, algae and daphnids did not take up the
particles.
Figure. 9: Feeding the animals with ZnO nanoparticles results in an
accumulation of the particles in the stomach tissue. TEM analysis of
this organ indicates that nanoparticles, found at the plasma
membrane of the cells facing the lumen, pass into the cytoplasm
and through the junctions (A). Clusters of ZnO nanoparticles can be
observed at the edge of zymogen granules (B), in the mitochondria
and scattered in the cytoplasm (C). Scale bars 0.5 μm.
WP5: Nanoparticle environmental impact. The biophysicochemical
behaviour of nanoparticles, and their ensuing bioavailability and
toxicity characteristics, strongly depends on the nature and the
extent of molecular interactions with organic and inorganic
materials in the environment. Wageningen together with an input
from Antwerp are responsible for analysing the influence of
chemical conditions and binding of particular species on the
biointeraction and bioaccumulation of nanoparticles. Wageningen
have extensive experience in the relationship between the
chemical speciation of dissolved and particulate material in
‘natural’ waters and its bioavailability. They are studying how the
nanoparticles and the nanoparticle-water interface is modified
when they enter a typical aqueous environmental system such as
river, estuarine and sea water and how this affects their biological
activity. Experiments are being carried out in laboratory controlled
and relevant microcosms. The rate of the actual transfer of oxide
nanoparticles across the cell membrane of a few selected aquatic
organisms (microorganisms, invertebrates and fish); in relation to
their local speciation and the physicochemical conditions at the
outer side of the biointerface will also be investigated. The
alteration of the nanoparticles during the in vivo experiments
described in (WP4) is being investigated in this section and related
to their effects. In the first half of the programme, studies have
mainly concentrated on the surface chemistry of SiO 2 particles and
their interaction with the soluble heavy metal ion Pb 2+ .
WP6: Integrated Modelling. No environmental toxicological study
is complete unless the various parts are integrated together in a
theoretical model. This is essential not only for planning the study
but also for assessing the final transfer parameters. Such a process
is continuously iterative throughout the investigation until towards
the end of the study, when the parameters are completely
optimised, and predictions as to the impact of the nanoparticles on
the aquatic environment can be made. The model is being
developed along the lines of previous environmental ecological
models which predicted the transport and fate of soluble
contaminants. A compartmental model is being used where the
compartments are represented by the cell membrane, cell
organelles, total cell, tissue and model aquatic organisms. The
model based on ECoS3 (developed by Plymouth Marine
Laboratory) allows the set-up and integration of sets of advection–
diffusion equations representing multiple constituents interacting
in a spatial context 3 . WP6 has developed working models of the
solubility of oxide NPs and the validity of these models has been
tested experimentally. The first step in the development of reliable
structure-activity toxicological predictive relationships has been
carried out and the modelling of the amount of NP that effectively
reaches an organism and is, subsequently, internalized by it, prior
to the toxic effect itself is taken care of using this model (see
Figure 10). The main advantage of this model is that it provides a
prediction of the amount of NP attached (or absorbed) and
internalized by a microorganism as a function of time, based on a
simple physicochemical mechanism.
3 Harris, J.R.W. & Gorley, R.N. 2005. ECoS, a framework for
modelling hierarchical spatial systems. Sci. Tot. Env. 314 –316:625–
635.
8 Compendium of Projects in the European NanoSafety Cluster