WP1 tasks and deliverables

Tasks:
Physical and chemical characterisation of MNMs provided by NANoREG (NMBU, SINTEF)
Implementation of MNM dispersion SOPs for environmental exposure media (SINTEF, NMBU)
Characterisation of MNMs in exposure media and organisms (NMBU, SINTEF)

Deliverables:
Validated SOP for obtaining reproducible and stable MNMs in aquatic (ecotoxicology) media.
SOPs for in vitro and in vivo toxicity studies (collaboration with WP2 and WP3).
Articles in peer reviewed literature (3-4 papers).

WP2 tasks and deliverables

Tasks: (All tasks go beyond NANoREG).
Validation of SOPs for cellular uptake (URI), proliferation, and cell death (impedance-based methods) (UiB), cytotoxicity, genotoxicity (NILU, CBT), mutagenicity (NILU); Bhas 42 CTA (NILU), the human lung transformation assay in vitro (hLCTA) (STAMI).
Validation of hLCTA for carcinogenic potential of MNMs by assessing tumorigenicity of transformed cells in nude mice. (Beyond the brief of the NANoREG project) (STAMI).
Setting up an ALI-exposure monoculture and co-culture model (NILU)
Development of novel HTS methods for evaluating uptake and intercellular transfer of MNM (UiB), genetic and epigenetic changes (NILU).
Development of micro-fluidic systems for high-throughput cell-based assays, which provide a quantitative spatial and temporal control of MNM dose and interaction time, and mimick in vivo physiological environment (UiB).
Identification of new sensitive molecular biomarkers by investigating perturbations (genetic, epigenetic and transcriptomic) in relevant biological pathways. (NILU, UiB, CBT, STAMI)

Deliverables:
Comparison, evaluation, and validation of proposed in vitro methods for assessing nanotoxicity.
Comparison of in vitro effects with published in vivo data from inhalation and ALI studies .
Identification of the most sensitive molecular biomarkers of carcinogenicity and tumorigenicity.
Ranking of MNMs according to cytotoxicity, genotoxicity, mutagenicity, transformational/tumorigenic ability; identification of physico-chemical characteristic responsible for toxicity.
SOPs for HTP methods for human-related in vitro toxicity assessment.
Publications in peer reviewed literature (5-7 papers).

WP 3 tasks and deliverables

Tasks:
Validation of aquatic and terrestrial ecotoxicity SOPs selected in NANoREG for determining acute toxicological responses at the cellular and individual levels (SINTEF, NMBU).
Determination of bioavailability, internal exposure and uptake of MNMs to aquatic and terrestrial organisms (NMBU, SINTEF).
Development and standardisation of HTP ecotoxicity approaches for algae, bacteria and C.elegans (SINTEF, NMBU).

Deliverables:
OECD aquatic and terrestrial toxicity levels, EC50/PNEC-values for different MNMs, ranking of toxicity of examined MNMs and within MNM classes (e.g. CNTs).
Bioaccumulation factors for examined MNMs.
Suggested SOPs for HTP ecotoxicity assessment.
Publications in peer reviewed literature (3-4 papers).

WP 4 Tasks and deliverables

Tasks:
Experiment with innovative methods of interdisciplinary communication to encourage information exchange and learning across the project partners and WPs at each of the annual project meetings
Facilitate researchers to anticipate potential challenges and identify available alternatives in their work and to reflect on important uncertainties, underlying values, and embedded assumptions
Explore potential for enhanced interaction and communication among toxicologists, technology developers, regulators and other relevant stakeholders to ensure mutual learning, dissemination of results and implementation of new or modified test strategies.

Deliverables:
Policy brief on challenges on the horizon for ensuring the health and safety of MNMs
Academic article on important uncertainties, assumptions and choices shaping our knowledge of the different impacts of MNMs on human health and ecosystems
Workshop with a range of relevant stakeholders to discuss the project’s approach and results
Proposed guidelines for regulatory bodies on robust and reliable MNM testing strategies

WP5 tasks

Yearly partner meetings will be organized to monitor progress and to plan joint activities, discuss results and cross cutting topics, prepare reports, common publications, etc. Altogether, 3 project meetings are planned, and in addition an open workshop with various stakeholders.
To promote faster transfer of knowledge and career development of young scientists, exchange of postdocs will be encouraged, e.g. between NILU/CometBiotech/ UiB/STAMI and NMBU and SINTEF.