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

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The exposures to be conducted will utilize a range <strong>of</strong><br />

environmentally relevant species in different exposure media<br />

<strong>and</strong> will measure a range <strong>of</strong> endpoints, thereby improving the<br />

current state-<strong>of</strong>-the-art. Variables such as aggregation <strong>and</strong><br />

dissolution <strong>of</strong> ENPs will be monitored in the test media using<br />

qualitative <strong>and</strong> quantitative methods. Our experiences will also<br />

allow us to recommend refinements to existing ecotoxicity test<br />

protocols for ENP studies <strong>and</strong> will provide information that can<br />

be used to investigate approaches for calculating predicted noeffect<br />

concentrations in WP 6.<br />

Obj.6: Establish <strong>and</strong> model how environmental physico-chemical<br />

properties in wastewater, natural waters <strong>and</strong> soil govern ENP<br />

parameters such as stability, soil–solution partitioning,<br />

downward transport <strong>and</strong> transformation (e.g. dissolution) that<br />

each may ultimately affect bioavailability to organisms.<br />

Baseline. The properties <strong>of</strong> the selected ENPs will be<br />

characterised in detail (in WP 1); however, the consequences <strong>of</strong><br />

these properties for behaviour <strong>of</strong> the ENPs in the natural<br />

environment (e.g. aggregation/dispersion, association with<br />

natural organic matter, binding to suspended sediments <strong>and</strong><br />

soils, dissolution rates) have so far not been studied. Although<br />

knowledge <strong>of</strong> the behaviour <strong>of</strong> natural metal oxides suggests<br />

that chemical factors (e.g. dissolved organic matter, pH, ionic<br />

strength) should influence the stability <strong>of</strong> metal oxide ENP, the<br />

bioavailability <strong>of</strong> ENPs to organisms has only been studied in<br />

simple or environmentally unrealistic systems, <strong>and</strong> it is unknown<br />

how these factors affect ENP uptake <strong>and</strong> toxicity. Work has<br />

been published showing that both pH <strong>and</strong> the presence <strong>of</strong><br />

naturally occurring macromolecules can influence the<br />

dissolution <strong>and</strong> aggregation <strong>of</strong> ENPs <strong>and</strong> it is likely that these<br />

affects may change bioavailability (Baalousha, et al. 2008;<br />

Diegoli, et al. 2008).<br />

NanoFATE progression beyond the “state-<strong>of</strong>-the-art”. In<br />

NanoFATE we will address the role <strong>of</strong> water <strong>and</strong> soil<br />

physicochemical properties <strong>and</strong> particle characteristics by<br />

determining the magnitude <strong>of</strong> ENP effects for key organisms<br />

exposed to different particle types <strong>and</strong> under different<br />

environmental conditions. Specifically we will adopt the<br />

following approach.<br />

1. Conduct tests to measure the toxicity <strong>of</strong> a selected set <strong>of</strong><br />

ENPs in a set <strong>of</strong> soils <strong>and</strong> waters <strong>of</strong> known physicochemical<br />

properties (VUA, UAVR, CU).<br />

2. Account for the role <strong>of</strong> dissolved metal in toxicity, by<br />

linking information on dissolution rates to predictions <strong>of</strong><br />

free metal ion concentration using the Windermere Humic<br />

Acid Model (WHAM) (Tipping 1984) or empirical<br />

relationships with either the free ion activity model (Morel<br />

1993), free ion effective dose model (L<strong>of</strong>ts et al. 2005,<br />

2006) or biotic lig<strong>and</strong> model, as a prediction <strong>of</strong> available<br />

exposure <strong>and</strong> associated effect (DiToro et al. 2001) (NERC,<br />

VUA, UAVR).<br />

3. Quantify additional toxicity (if any) beyond that predicted<br />

to be caused by the free metal ion.<br />

NanoSafetyCluster - Compendium 2012<br />

4. Use multivariate statistical methods such as principal<br />

component analysis <strong>and</strong> partial least squares regression to<br />

investigate the relationships between ENP derived toxicity<br />

<strong>and</strong> soil <strong>and</strong> water chemistry (VUA, NERC, UAVR).<br />

5. Investigate the use <strong>of</strong> rate transfer constants as a means to<br />

account for dissolution <strong>and</strong> the subsequent transfer <strong>of</strong> the<br />

causation <strong>of</strong> toxicity from ENP to free metal ion forms<br />

(VUA, NERC).<br />

Meeting this objective will require integrative working among<br />

ecotoxicologists <strong>and</strong> environmental <strong>and</strong> physical chemists. We<br />

will need to quantify how physical properties <strong>of</strong> ENPs change<br />

with time in diverse chemical environments <strong>and</strong> how this affects<br />

ENP exposure. The information derived from these studies will<br />

allow us to modify assessments <strong>of</strong> risk in receiving waters <strong>and</strong><br />

soils made in WP 6.<br />

Obj.7: Establish the mechanisms <strong>of</strong> uptake, internal trafficking<br />

<strong>and</strong> toxicity <strong>of</strong> ENPs.<br />

Baseline. To date, information on the toxicokinetics <strong>of</strong> ENPs is<br />

very sparse. Very little is known <strong>of</strong> their uptake, internal<br />

trafficking <strong>and</strong> distribution <strong>and</strong> the effects <strong>of</strong> ENP properties on<br />

these parameters. This is despite the fact that these aspects are<br />

important to underst<strong>and</strong> mechanisms <strong>of</strong> action <strong>and</strong> long-term<br />

effects <strong>of</strong> ENPs.<br />

In relation to mechanisms <strong>of</strong> toxicity, some observations do<br />

indicate that nanoscale materials used in biomedical <strong>and</strong><br />

pharmaceutical research may modulate the expression <strong>of</strong><br />

cancer genes (Omidi et al., 2003), <strong>and</strong> genes involved in cell<br />

signalling (Regnstrom et al., 2006). For ENPs, recent studies<br />

have indicated genotoxicity <strong>and</strong> cytotoxicity in cultured human<br />

cells <strong>and</strong> generation <strong>of</strong> pulmonary fibrosis <strong>and</strong> lung tumours in<br />

rats (Wang et al., 2007). Such effects have, however, only<br />

recently been studied in aquatic organisms (see review <strong>of</strong><br />

Moore, 2006; also Klaper et al. 2009; Shinohara et al. 2009) <strong>and</strong><br />

we know <strong>of</strong> no published genotoxic studies in terrestrial<br />

invertebrates (although NERC have submitted a paper on ENP<br />

immunotoxicity in earthworms) <strong>and</strong> only a single molecular<br />

toxicity study for terrestrial plants (Lee et al. 2009).<br />

Compendium <strong>of</strong> Projects in the European NanoSafety Cluster 99<br />

A

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