Contract Agreement: Fp7 no: 309329 Website: www.nanosolutionsfp7.com Coordinator: FIOH
Table 1 Consortium List.
No. Beneficiary name Short name Country
1 TYOETERVEYSLAITOS FIOH Finland
2 KAROLINSKA INSTITUTET KI Sweden
3 UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN NUID UCD Ireland 4 NEDERLANDSE ORGANISATIE VOOR TOEGEPAST NATUURWETENSCHAPPELIJK
ONDERZOEK - TNO
TNO Netherlands
5 UNIVERSITE BORDEAUX UB France
6 UNIVERSITY COLLEGE LONDON UCL United Kingdom
7 UNIVERSITY OF PLYMOUTH UOP United Kingdom
8 HERIOT-WATT UNIVERSITY HWU United Kingdom
9 ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOMATERIALES CIC biomaGUNE Spain
10 LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN LMU MUENCHEN Germany
11 INSTITUTE OF OCCUPATIONAL MEDICINE IOM United Kingdom
12 TURUN YLIOPISTO U. TURKU Finland
13 TEKNOLOGIAN TUTKIMUSKESKUS VTT VTT Finland
14 ACONDICIONAMIENTO TARRASENSE ASSOCIACION LEITAT Spain
15 DANMARKS TEKNISKE UNIVERSITET DTU Denmark
16 FONDAZIONE TELETHON FTELE.IGM Italy
17 UNIVERSITAET LEIPZIG ULEI Germany
18 EIDGENOESSISCHE MATERIALPRUEFUNGS- UND FORSCHUNGSANSTALT EMPA Switzerland
19 BIOBYTE SOLUTIONS GMBH BIOBYTE Germany
20 INSIGHT PUBLISHERS LIMITED IPL United Kingdom
21 PLASMACHEM PRODUKTIONS- UND HANDEL GMBH PLASMACHEM Germany
22 INKOA SISTEMAS SL INKOA Spain
23 BIOTESYS GMBH BIOTESYS Germany
24 Zhejiang University ZJU China (People's
Republic of)
25 Fundação Universidade de Brasilia UNB Brazil
26 NATIONAL HEALTH LABORATORY SERVICES NIOH South Africa
27 NOORDWES-UNIVERSITEIT NWU South Africa
28 NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH NIOSH United States 29 SAIC - FREDERICK INC CORPORATION SCIENCE APPLICATIONS INTERNATIONAL
CORPORATION
NCL United States
30 NANOCYL SA NANOCYL Belgium
31 NANOLOGICA AB NANOLOGICA Sweden
32 UNIVERSITA DEGLI STUDI DI SALERNO NeuRoNe Italy
33 SOLVAY SA SOLVAY Belgium
34 POLYMER FACTORY SWEDEN AB POLYMERFACTORY Sweden
35 POLIMEROS Y SISTEMAS DE APLICACION TECNICA SL POLYSISTEC, S.L. Spain 36
37
UNIVERSITY OF MANCHESTER MISVIK BIOLOGY
UNIMANT MISVIK
UK * Finland**
* replaced UCL , partner 6; ** replaced VTT, partner 13
Contents
1 Summary ... 167 2 Background ... 167 3 Scientific and technological challenges ... 167 4 Objectives ... 167
5 Progress and Outcomes to date ... 167 6 Expected Impact ... 168 7 Directory ... 168 8 Copyright ... 169
1 Summary
Project Duration: 1.4.2013-31.3.2017
Project Funding: Fp7 GA contract no 309329, € 10 000 000
The overarching aim of the NANOSOLUTIONS consortium is to provide a means to develop a safety classification for engineered nanomaterials (ENM) based on an understanding of their interactions with living organisms at molecular, cellular and organism levels. The objective is to determine the “biological identity” of ENM, and subsequently develop a proof of concept that can predict from the properties of ENM their ability to cause health or environmental hazards.
2 Background
Engineered nanomaterials (ENM) have attracted a great deal of interest over recent years and their potential for economic exploitation has risen exponentially. Some of their properties however have given rise to concern that they may be harmful to humans. Scientists, regulators and industry need an effective test of these properties in order to be sure they are safe to use. While testing of individual applications of ENM is possible, it is expensive and time-consuming and is a barrier to innovation. By identifying those characteristics of ENM that determine their biological hazard potential it will be possible to create a set of biomarkers of their toxicity that will assess and predict their safe use.
3 Scientific and technological challenges
The way ENM interacts with living organisms is complex and their biological effect is largely governed by their surface properties and the way different biomolecules bind to this surface. By understanding the fundamental characteristics of ENM underpinning these biological effects NANOSOLUTIONS will provide a sound foundation on which to classify the materials according to their safety. In other words, NANOSOLUTIONS will investigate how ENM interact with living organisms at a molecular, cellular and organism level based on their material characteristics.
In determining the biological identity of ENM the project will develop a computational model that will predict from the properties of ENM their ability to cause harmful health or environmental hazards. This will give scientists the ability to predict these harmful effects rather than simply describe them once they have occurred.
4 Objectives
The main objective of NANOSOLUTIONS is to identify and elaborate those characteristics of ENM that determine their biological hazard potential. This potential includes the ability of ENM to induce damage at the cellular, tissue, or organism levels by interacting with cellular structures leading to impairment of key cellular functions. These adverse effects may be mediated by ENM-induced alterations in gene expression and translation, but may involve also epigenetic transformation of genetic functions. By determining the biological identity of ENM, the project will create a set of biomarkers of ENM toxicity that are relevant in assessing and predicting the safety and toxicity of ENM across species. This computational, predictive tool will become the global standard for ENM safety classification.
5 Progress and Outcomes to date
The Nanosafety Classifier is taking shape
The work on life-cycle analysis of nanomaterials has advanced greatly (WP4). Simulation of the engineered nanomaterials (ENMs) release and release characterization at laboratory scale have been set up for a variety of applications ranging from sportswear textiles to motor oil additives. Also, the basis for deriving the effect factors of nanomaterials and their application of the LCA case study for quantum dots has been established. These observations pave the way for a similar analysis of other types of nanomaterials.
One of the major objectives has been carrying out the experimental work to test the ENM and generate data on ENM interactions with living systems for the Classifier; this work has been performed in WP5-WP9 and further studies are still underway. For the first time, the relevance of the glycosylation on the bio-nano interactions has been shown. The work also highlighted the significance of a protein corona on nanoparticles in modulating particle properties and their biological interactions.
The study shows that the post-translational modification of proteins can significantly impact nanoparticle–cell interactions by modulating the protein corona properties (WP5).
Results from WP6 (Cell models) have highlighted dose- and time-dependent effects of the tested ENMs, but also underscored that different surface functionalizations of ENMs have distinct effects on the toxicity in different cellular models including macrophages, lung cells, T cells, and mesenchymal stem cells. In WP7 (Cross-species models) a toxicity screen has been attempted with all materials for two model organisms – microbes (E. coli) and the water flea (D. magna) to determine low, medium and high toxicity materials. In the test conditions, the CdTeQDs were observed to be
the most toxic from all the tested nanomaterials to microbes. The used test models enabled identification of the most toxic nanomaterials over species.
In WP8 (Disease models) the data shows that the surface functionalization of quantum dots determines their association with atherosclerotic lesions in the carotid artery of ApoE-/- mice fed a high-cholesterol diet. Also, it has been discovered that in asthmatic mice, core CuO exposure activates innate immunity reactions while it diminishes T-cell mediated adaptive immunity response. In WP9, translocation studies have been conducted across different barriers at cellular, tissue, organ and organism level. It has been observed that the surface functionalization of nanomaterials determines their behaviour across endothelia barriers and cell membranes and influences on nanoparticle uptake.
OMICS methods have been addressed in detail. The omics assessment is progressing well, and for the transcriptomics part, the data production is advancing rapidly (WP10). In addition, the project has developed the computational framework for the Nanosafety Classifier and agreed on the data formats and data repository (WP11). The Classifier will highlight the most relevant features that, across the data layers, will predict the safety of the nanomaterials and classify against the effect. A novel computational method has been developed for feature selection and prioritization from omics data based on fuzzy logic and random forests approaches. The method is able to retrieve very robust sets of features. The WP12 (Safety classification) has carried out an option analysis of the Classifier. It will facilitate further the development of the Classifier concept and design through the prototyping and testing of the tool, and it will also develop a specification for a high throughput system for future testing and analysis. Thus, the computational infrastructure of the Classifier is in place, and the prototype is currently being tested. The promises and the potential of the NANOSOLUTIONS Project seem to be very
encouraging now when the Project is starting its final year of work.
The NANOSOLUTIONS project also provides by far largest OMICs data resource against highly characterized set (n=30) of carefully selected ENMs for further studies. The results of the project and ultimately the Classifier will enable a remarkable progress in the grouping of nanomaterials based on their hazard and other features.
In order to facilitate the dissemination of research results and promote topical discussion on nanosafety, the project has organized two large international Conferences, such as the International Congress on Safety of Engineered Nanoparticles and Nanotechnologies (www.ttl.fi/senn2015) in Helsinki 12-15 April 2015, and Systems Biology in Nanosafety Research Conference in Stockholm 9-10 November 2015.
6 Expected Impact
The main innovation of the NANOSOLUTIONS project has been envisioned to be the development of the engineered nanomaterial (ENM) safety classifier. This novel hazard profiling principle will provide a basis that enables us to understand and define the toxic potential of all types of ENM. It will be used by companies that manufacture ENM and by a regulatory community to manage, reduce uncertainty, and clarify the current debate, since it will provide the potential to effectively “de-classify” many types on ENM in many applications, in terms of safety risks. The NANOSOLUTIONS ENM safety classification model will benefit industry and enable innovation, since being able to effectively assess the safety characteristics of ENM will speed up the innovation cycle and the development of commercially viable products using ENM.
7 Directory
Table 1 Directory of people involved in this project.
First Name Last Name Affiliation Address e-mail
Kai Savolainen FIOH Finland kai.savolainen@ttl.fi
Bengt Fadeel KI Sweden bengt.fadeel@ki.se
Juha Kere KI Sweden juha.kere@ki.se
Roman Zubarev KI Sweden roman.zubarev@ki.se
Kenneth Dawson NUID UCD Ireland kenneth.a.dawson@cbni.ucd.ie
Ingeborg Kooter TNO Netherlands ingeborg.kooter@tno.nl
Didier Astruc ISM France d.astruc@ism.u-bordeaux1.fr
Kostas Kostarelos UOM United Kingdom kostas.kostarelos@manchester.ac.uk
Richard Handy UOP United Kingdom r.handy@plymouth.ac.uk
Teresa F Fernandes HWU United Kingdom t.fernandes@hw.ac.uk
Sergio E. Moya CIC Biomagune Spain smoya@cicbiomagune.es
Fritz Krombach LMU Germany krombach@med.uni-muenchen.de
Lang Tran IOM United Kingdom lang.tran@iom-world.org
Riitta Lahesmaa U. TURKU Finland riitta.lahesmaa@btk.fi
Roland Grafström KI Sweden roland.grafstrom@gmail.com
First Name Last Name Affiliation Address e-mail
Socorro Vázquez Leitat Spain svazquez@leitat.org
Katrin Löschner DTU Denmark kals@food.dtu.dk
Paola Cormio FTELE.IGM Italy p.cormio@tigem.it
Irina Estrela-Lopis ULEI Germany irina.estrela-lopis@medizin.uni-leipzig.de
Peter Wick EMPA Switzerland peter.wick@empa.ch
Ivica Letunic BIOBYTE Germany letunic@biobyte.de
William Davis IPL Belgium wdavis@ipl.eu.com
Alexei Antipov PLASMACHEM Switzerland antipov@plasmachem.com
María Blázquez INKOA Spain maria@inkoa.com
Jürgen Bernhardt BIOTESYS Germany bts@biotesys.de
Changyou Gao Prof. cygao@zju.edu.cn
Paulo Cesar De Morais UNB Brazil pcmor@unb.br
Mary Gulumian ZJU South Africa mary.gulumian@nioh.nhls.ac.za
Victor Wepener ZJU South Africa victor.wepener@nwu.ac.za
Scott E. McNeil NIOSH / NCL USA ncl@mail.nih.gov
Julie Muller NANOCYL Belgium julie.muller@nanocyl.com
Roberto Hanoi Labrador NANOLOGICA Sweden hanoi@nanologica.com
Roberto Tagliaferri UNIMANT Italy rtagliaferri@unisa.it
Jacques-Aurélien Sergent SOLVAY Belgium jacques-aurelien.sergent@solvay.com
Andreas Nyström POLYMERFACTORY Sweden andreas.nystrom@polymerfactory.com
Jordi Férnandez POLYSISTEC Spain export@polysistec.com
8 Copyright
© 2017, FIOH on behalf of the NanoSOLUTIONS consortium.
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