Nanomaterials Upptag Och Spridning I Kroppen Och Miljön, Svenska

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Svenska myndigheter och nanomatrial PM 3/15 Nanomaterials upptag och spridning i kroppen och miljön kemikalieinspektionen.se Kemikalieinspektionen är en myndighet under regeringen. Vi arbetar i Sverige, inom EU och internationellt för att utveckla lagstiftning och andra styrmedel som främjar god hälsa och bättre miljö. Vi har tillsyn över reglerna för kemiska produkter, bekämpningsmedel och ämnen i varor och gör inspektioner. Vi granskar och godkänner bekämpningsmedel innan de får användas. Vårt miljökvalitetsmål är Giftfri miljö. © Kemikalieinspektionen, Stockholm 2015. Artikelnummer: 511 153. Förord Kemikalieinspektionen har på uppdrag av regeringen tagit fram en handlingsplan för en giftfrivardag Handlingsplan för en giftfri vardag 2011– 2014 – Skydda barnen bättre. Insatser sker nu på flera områden både nationellt, inom EU och internationellt och ofta i samarbete med andra myndigheter. Att minska kemiska risker i vardagen är ett steg på vägen att nå riksdagens miljökvalitetsmål Giftfri miljö – det mål Kemikalieinspektionen ansvarar för. Inom ramen för handlingsplanen tar KemI fram sammanställningar som publiceras i Kemikalieinspektionens rapport respektive PM-serie. Publikationerna, som är kostnadsfria, finns på webbplatsen www.kemikalieinspektionen.se I Kemikalieinspektionens handlingsplan för en Giftfri vardag 2011-2014 framhålls behovet av insatser för att nå en hög skyddsnivå för eventuella hälso- och miljörisker orsakade av nanomaterial. Som ett led i arbetetet sammankallades myndigheter/statliga aktörer vars verksamheter är berörda av nanoteknik och nanomaterial till ett fjärde möte för kunskaps- och erfarenhetsutbyte samt diskussion. Myndighetsmötet ordnades denna gång i samarbete med Nordiska Nanomaterial Gruppen sponsrat av Nordiska Kemikalie Gruppen (NKG). Mötet bestod av en gemensam workshop på förmiddagen och ett myndighetsmöte med nordiska deltagare på eftermiddagen. Föreläsarna har själva bidragit med sammanfattningar från sina presentationer. I detta PM ingår bidrag från Kungliga Tekniska högskolan, Danska Miljöstyrelsen, Totalförsvarets forskningsinstitut, Lunds Universitet, representanter för OECD och EU kommissionen, Läkemedelsverket, Kemikalieinspektionen och Miljödepartementet. Samordning av arbetet och sammanställning från mötet har gjorts av Lena Hellmér, Kemikalieinspektionen. Ansvarig för arbetet var Lisa Anfält, chef för enheten EU koordinering på Kemikalieinspektionen. Innehåll Inledning............................................................................................................ 5 Summary ........................................................................................................... 6 1 Sammanfattningar från föredragen ..................................................... 9 Nanomaterials in a Life Cycle Perspective .................................................................................... 9 Dermal absorption of nanomaterials ............................................................................................. 9 Interactions of nanoparticles with organs protected by internal biological barriers ..................... 10 Measurement Techniques for Airborne Nanoparticles ................................................................ 11 Effekter efter inandning av metalloxider i friska och känsliga individer ....................................... 12 Nanosäkerhet ur ett EU- och OECD perspektiv .......................................................................... 13 Update on NM projects for the method, guidance and testing strategy development in the OECD Test Guidelines programme .......................................................................................... 14 Nytt om nano från Kemikalieinspektionen ................................................................................... 15 Nanomaterial i kosmetiska produkter – vad har hänt sedan de nya reglerna infördes? ............. 15 Danske aktiviteter vedr. nanomaterialer ...................................................................................... 16 Nanocellulose and NANoREG- project ....................................................................................... 17 2 Bilagor ................................................................................................. 19 Bilaga 1. Deltagarlista.................................................................................................................. 19 Bilaga 2. Föreläsarnas power-point presentationer .................................................................... 21 Inledning Detta PM är en sammanställning av det fjärde myndighetsmötet om nanoteknik och nanomaterial Syftet med mötet som redovisas i detta PM var att få kunskap om aktuell forskning och de frågor som svenska och statliga aktörer arbetar med inom nanoområdet samt att fortsätta utveckla myndighetsnätverket. Denna gång deltog även forskare och myndighetsrepresentanter från övriga Norden. En inbjudan till myndighetsmötet skickades till samtliga departement inom Regeringskansliet och de statliga myndigheter eller offentliga finansiärer som bedömdes ha aktiviteter eller intressen med anknytning till nanomaterial och nanoteknik i Sverige. Totalt deltog 49 personer från 24 aktörer på seminariet den 27 november 2014. Dessa var Bioforsk, Danmarks tekniska universitet, Europeiska kommissionen, Finska Arbetshälsoinstitutet, Totalförsvarets forskningsinstitut (FOI), Formas, Försvarets materielverk, Försvarsmakten, Generalläkaren, Kemikalieinspektionen, Kommerskollegium, Kungliga Tekniska högskolan (KTH), Livsmedelsverket, Lund universitet, Läkemedelsverket, Naturvårdsverket, Norwegian institute for water research, norska Miljødirektoratet, OECD sekretariat, Regeringskansliet, SINTEF Materials and Chemistry, Socialstyrelsen, Danska miljöstyrelsen och Trafikverket. Workshopen/seminariet hölls omväxlande på engelska och ”skandinaviska” och därför varierar språket även i rapporten. Som moderator för mötet fungerade Gregory Moore från Kemikalieinspektionen. Introduction This PM is a compilation of speeches made at the fourth network meeting with authorities on nanotechnology and nanomaterials. The purpose of the meeting accounted for in this PM was to acquire knowledge about current research and topical questions at Swedish and government authorities within the nano area and to continue developing the authority network on nanotechnology and nanomaterials. Participants at this meeting were researchers and authority representatives from the Nordic countries and the invitation was sent to all Swedish ministries and official financiers estimated to carry out activities or having interests in nanotechnology and nanomaterials in Sweden. 50 participants from 26 actors participated at the seminar on 27 November 2014, which was held alternately in English and a Scandinavian language and that is why the language varies in the report too. Moderator of the meeting was Dr. Gregory Moore, the Swedish Chemicals Agency. 5 Summary David Lazarevic, from KTH gave an introductory lecture on Nanomaterials in a Life Cycle Perspective. Engineered nanomaterials are being used in a growing number of products. The assessment of the impacts, or benefits, upon human health and the environment should be conducted from a life cycle perspective. However, current assessments are inadequate due to the lack of data on the emissions from engineered nanomaterials and nanoparticles during the production, use and disposal phases of a product life cycle, and the lack of characterisation factors for nanomaterials in life cycle impact assessment models. From the Danish EPA Anne Mette Zenner Boisen, presented two projects on dermal absorption of nanomaterials. The literary project from 2013 performed a scientific appraisal of the reliability and relevance of available studies on dermal absorption using Klimisch criteria and nanomaterial characterisation, database available from the Danish EPA. Recommendations include that study designs (in vivo and in vitro) should consist of a sufficient post-exposure duration to account for potential lag-times of dermal absorption. An experimental project on dermal absorption of TiO2 and ZnO in a realistic exposure scenario using in vitro and in vivo test methods is ongoing and will be published in 2015. Anders Bucht introduced us to the area of interactions of nanoparticles with organs protected by internal biological barriers. Inhalation of nanoparticles leads to surface adsorption of biomolecules in the lung lining fluid that influence responses of cells in the lung epithelium and uptake in the body. When translocated into the blood circulation a corona of blood plasma proteins will be formed which can activate the contact dependent coagulation system. This activation may elicit tromboinflammation, blood clot formation, as well as activate innate and adaptive immune responses. The important topic of Measurement Techniques for Airborne Nanoparticles was presented by Jakob Löndahl, Lund University. A major pathway for exposure to nanoparticles is through the air during breathing. Thus, it is necessary to have adequate monitoring techniques that ideally are able to separate engineered nanoparticles from the background. There is a range of instrumental options for measurement of airborne nanoparticles, but often it is necessary to choose between simplicity and accuracy (or high time resolution and relevant particle characteristics). It is still also difficult to measure relevant exposure metrics such as only the engineered nanoparticles. However, new methods are emerging that might overcome this problem at least partly. Åsa Gustafsson held a presentation about her thesis entitled ”Nanomaterials, respiratory and immunological effects following inhalation of engineered nanoparticles”. It shows that exposure to nano sized titanium dioxide (TiO2) induced long-lasting immune response in the airways. The long-term activation of the immune system could potentially trigger the development of diseases. The particles that were deposited in the alveolar region were also retained in the lung for a long time, up to three months after exposure. By comparing different inbred rat strains it was demonstrated that genetically determined factors influence the immune and respiratory responses to TiO2. An important issue of this thesis was to study the responses in sensitive individuals. These sensitive individuals were represented by groups of animals with an allergic airway inflammation or by rat strains that were genetically susceptible to inflammatory disorders. One study showed that when the mice were exposed to particles and an allergen during the same period, a decline in general health was observed. Altogether, this thesis emphasises the complexity of assessing health risks associated with nanoparticle exposure and the importance of including sensitive populations when evaluating adverse health effects of ENMs. 6 Eva Hellsten, former Head of the Chemicals unit at the European Commission, vice president in the OECD WPMN, and member of the Swedish Nano Commission, informed about nanosafety from an EU and OECD perspective and her experiences in the area. Within the EU, work on health and environment safety aspects of nanomaterials started in 2004. Via the EU research programmes, 25 million Euros have been invested each year in this area. The EU legislation has been reviewed to analyse in which ways legislation needs to be adapted to better cover nanomaterials. For legislative purposes adaptation of existing test methods is needed, e.g. testing of (eco)toxicology, exposure and measurements. Work to ensure that test methods are standardised and internationally harmonised is on-going within the OECD WPMN since 2006. In Sweden, a Government Nano Commission was initiated in 2012. The conclusions from this investigation (SOU 2013:70) stresses the importance of additional Swedish efforts in participating in EU and OECD work, as well as improved co-ordination and communication between Swedish authorities, academia industry and civil society. A Nano Council, with a Nano Centre as secretariat, was proposed to be established for this purpose. Jukka Ahtiainen, presently Senior researcher at the OECD secretariat continued with the topic and gave an update on NM projects for the method, guidance and testing strategy development in the OECD Test Guidelines programme. The OECD test guidelines for testing chemicals have been widely used for regulatory purposes all over the world since the establishment of the MAD principle in 1984. This Mutual Acceptance of Data ensures that if a chemical is tested under the GLP conditions according to an OECD Test Guideline, the data should be accepted in all OECD countries. The rationale behind this agreement is to save resources and avoid especially duplicate vertebrate testing. Eventually the OECD test methods are referred to or taken into the national chemicals legislation such as the test method regulation (440/2008/EU) in the European Union. Sofia Tapper from the Swedish Ministry of the Environment and Energy informed among other things about the Nano Commission and an action plan for safe use and handling of nanomaterials. The new Swedish government has shown interest in the commission and its conclusions and intends to continue pressing the European Commission for the importance of adequate EU-rules on nano materials. Work on establishing a possible Nano Centre or Nano Council continues. Elin Simonsson, the Swedish Chemicals Agency, briefly presented ongoing work at the agency on nano materials, i.e. amendments of REACH annexes, overview of the EU Commission recommended definition of nanomaterials and its survey of consequences with regard to measures for increased transparency of nanomaterials on the market. Tomas Byström, the Swedish Medical Products Agency, informed about the rules on nanomaterials in cosmetic products, which came into force in 2013. Some regulatory support is, however, lacking with regard to approved substances in nano form. Within the EU; 25 000 cosmetic products and nanomaterials have been notified. The European Commission will within short publish a catalogue listing nanomaterials used in cosmetic products. Flemming Ingerslev, gave an account of the activities of the Danish Environmental Protection Agency - 6 million DKK have been allocated per year during 2012-2015 to ”Bedre styr på nano”, with the overall aim to get an overview of where in Denmark there may be a risk to consumers and the environment from the use of nano products. 7 - - One part of the effort included to set up a register of consumer products releasing nanomaterials. Danish manufacturers have to report their production and import of nano products aimed for consumers to this register. A number of other projects are also included in the work, from which reports are published continuously. Denmark also contributes to the OECD work on developing ecotoxicological methods for testing nano materials. How can authorities make use of the results of nano research and how can authority work have an effect on research? Jukka Ahtiainen opened the discussion by presenting the Finish participation in the NANoREG project.The safety of nanomaterials is investigated in the EU’s just-beginning extensive NANoREG project as a joint effort by the authorities and the industry. Finland’s goal in the project is to continue to study the safety of microfibrillar and nanofibrillar cellulose. In Finland, participation in the NANoREG project is coordinated by the Finnish Safety and Chemicals Agency (Tukes) that is also responsible for oversight and guidance concerning the REACH regulation. Also included in the project are the Finnish Institute of Occupational Health, responsible for the experimental in vitro and in vivo studies, and Stora Enso and UPM as a joint Nordic Cellulosa consortium. Finland’s national research portion of the Nanoreg project focuses on microfibrillar and nanofibrillar cellulose materials that have several potential industrial applications in different products. Microcellulose and nanocellulose comprise wood fibre and fibre bundles originating from wood cellulose. The intention is to study the safety of biodegradable microcellulose and nanocellulose experimentally by means of biological testing. This is important in order for it to be possible to use nanocellulose, for example, as raw material for cosmetics, food additives or packaging. The ensuing discussion raised the cooperation between the OECD and NANoREG, the design of a possible Nano centre in Sweden and ways in which Nordic colleagues treat different aspects of nanomaterials. In conclusion, it was agreed that a combination of a Nordic workshop and authority meeting was fruitful, particularly with respect to the discussions. The moderator extended his thanks to speakers and participants. 8 1 Sammanfattningar från föredragen Nanomaterials in a Life Cycle Perspective David Lazarevic, PhD, Researcher, KTH Nanotechnology and nanomaterials have been promoted as having the potential to bring benefits to many areas of research, and to positively contribute to sustainable development. As such, this rapidly growing field is increasing attracting investments from governments and businesses worldwide. However, it is also recognised that engineered nanomaterials may pose a risk to human health and the environment. There is a general consensus that the potential health and environmental risks of engineered nanomaterial should be evaluated over their entire life cycle. Life cycle assessment is one tool which has been promoted for such an evaluation. This work reviewed the literature on the application of life cycle assessment to engineered nanomaterials to identify current research and difficulties in applying life cycle assessment in this field. Twenty five LCA studies of nanomaterials were identified, including nanomaterial such as cadmium telluride, calcium carbonate, carbon black, carbon nanofibres, carbon nanotubes, nanoclay, nanoscale platinum-group metals, silica, silver, silicon, titanium and titanium oxide. Product systems studied include: auto-body panels, biopolymers, coatings, electronic displays, electronic sensors, lithium-ion batteries, photo voltaic systems, packaging and agriculture polymer films, nanomaterial production processes, textiles and wind turbine blades. These studies only looked at parts of the life cycle, with no quantitative studies addressing the impact of nanomaterials to human health and the environment from the cradle to the grave. Results from these studies showed the potential for a significant cumulative energy demand in the production of nanomaterials such as carbon nanotubes and carbon nanofibres. However, this is reduced when taking into consideration the small amounts of nanomaterials in products and the potential benefits during the use phase, such as weight reduction. Due to the different properties and functions of engineered nanomaterials when compared to conventional materials and products, special attention is required during the goal and scope definition phase in order to obtain meaningful results. The life cycle inventories of current LCA studies cannot be classified as comprehensive as they often lack nanomaterial specific data related to the outputs of processes. Hence, populating life cycle inventory databases with nanomaterial specific information, such as size and shape, is of critical importance. Although the UNEP/SETAC framework for toxic impacts can in principle be used for specific impacts causes by nanoparticles, life cycle impact assessment methods currently lack characterisation factors for the release of nanoparticles indoors and outdoors. Hence, no LCA studies to date have considered the human toxicity and eco-toxicity of nanomaterials from a life cycle perspective with consideration of the nano-specific properties. Dermal absorption of nanomaterials Anne Mette Zenner Boisen,PhD Danish Ministry of the Environment Under the Danish Nano Initiative ‘Better Control of Nano’ the Danish Environmental Protection Agency (EPA) has initiated a series of projects with the aim of further clarifying possible risks to consumers and the environment from nanomaterials. Two of these projects investigating dermal absorption of nanomaterials were presented at the workshop on 27th November 2014. 9 The first, Danish EPA Environmental Project No. 1504, 2013 was a literary project conducted in 2013 by the Institute of Occupational Medicine IOM, UK. The project performed a scientific appraisal of the reliability and relevance of available studies on dermal absorption using Klimisch criteria and nanomaterial characterization (as described in Card and Magnuson 2010). The appraised studies are available in a database, which can be found in a link within the project report (original version). A link to an updated version of the database, which included more studies were also performed in 2013 and can be found on the Danish EPA website (mst.dk). This update did not change any of the conclusions found in the project report. Results from the project showed that a very low dermal absorption of nanomaterials is possible in some cases; Nano-specific characteristics that may influence dermal absorption include size, shape and surface chemistry; test method(s) which most closely simulate the transport of nanomaterials through human skin are evaluated in the report and research gaps concerning dermal absorption of nanomaterials are described. It has been noted in several studies that there can be a considerable lag time between application of a test substance and appearance in the circulation. Gulson et al. 2010 noted a lag time of ~30 h before the first detection of 68Zn in the blood and urine of human volunteers. Therefore one recommendation from the project is that study designs (in vivo and in vitro) should consist of a sufficient postexposure duration to account for potential lag-times. The second project, which is experimental is ongoing and will be concluded in the summer of 2015. This project is conducted by Aarhus University in Denmark. The main goal of this project is to investigate if TiO2 and ZnO nanoparticles are able to penetrate the skin in a realistic exposure scenario. Sun screen is used as the vehicle and 2.5% nanoparticles by weight are added to the sunscreen. The Main goal of the project is to investigate if TiO2 and ZnO nanoparticles are able to penetrate the skin in a realistic exposure scenario. Nanospecific characteristics investigated in the project are size and coating. Test methods include: The in vitro Epiderm model; An in vivo mouse inflammation model and an in vivo mouse xenograft transplantation model with human skin. The results from this project will be published in peer-reviewed scientific articles and in a Danish EPA project report in 2015. Interactions of nanoparticles with organs protected by internal biological barriers Anders Bucht, Division of CBRN Defence and Security, Swedish Defence Research Agency, and Department of Respiratory Medicine, Umeå University. The widespread exploitation of new types of nanoparticles in a variety of industrial applications and cosmetics has raised concerns about toxicity when dispersed in occupational and public environments, especially when humans are exposed by the inhalation route. We and others have demonstrated cellular uptake of titanium dioxide nanoparticles (TiO2 NP) when exposed to lung epithelial cells, and that the NP interactions with the cells results in inflammatory responses and oxidative stress ( 1 2). The ability of NPs to translocate intracellularly and activate cells is, however, highly dependent on particle properties (e.g. size, crystal structure surface chemistry and agglomeration), cell culture conditions and type of responder cells. For example, addition of serum proteins to cell cultures will greatly influence the responses to the NPs, most likely due to formation of a protein corona on the surface of the particles. The composition of biomolecules adsorbed on the surface will 1 Ekstrand-Hammarström B, Akfur CM, Andersson PO, Lejon C, Österlund L and Bucht A. Nanotoxicology 2012, 6:623-634 2 Andersson PO, Lejon C, Ekström Hammarström B, Akfur C, Bucht A and Österlund L. Small 2011,7:514-23 10 gradually shift when particles translocate into the cells, i.e. when exposed through the airways the NP corona will initially consist of components of the lung lining fluid and after cellular uptake biomolecules from the cell interior will attach to the particles. When NPs are further translocated into the blood circulation, a corona of blood plasma proteins will be formed, including components of the complement and the coagulation systems. Detailed analysis of adsorbed plasma proteins bound to TiO2 particles after incubation with human plasma has shown enrichment in proteins of the contact dependent coagulation system on the surface. Using a whole-blood model utilizing fresh non-anticoagulated human blood, it was shown that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact coagulation system, which in this model elicits thromboinflammation and blood clot formation ( 3). These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. From that study it was concluded that TiO2 NPs, generally considered to be relatively harmless, are highly thrombogenic when they enter the body and cross epithelial and endothelial borders. Such activation may potentially induce immune activation, inflammation and tissues damage in vivo. Measurement Techniques for Airborne Nanoparticles Jakob Löndahl, Div. of Ergonomics and Aerosol Technology, Lund University The rapidly growing nanotechnology sector has resulted in an increasing need to understand health risks associated with exposure to the new materials emerging. A major pathway for exposure is through the air during breathing. To investigate, control and limit airborne exposure to nanoparticles it is necessary to have adequate measurement techniques. Such techniques should ideally be able to separate engineered nanoparticles from the background and to measure the most relevant particle properties. Relevant particle properties may for instance be size, shape, surface area, chemical composition, solubility and biological activity. Among the easiest real time techniques to use are the instruments based on electrical charge. These measure particle number and/or surface area with reasonable accuracy, but are generally not able to sort out particles smaller than 100 nm. More advanced instruments include for instance the scanning mobility particle sizer (SMPS), the electrical low pressure impactor (ELPI), the aerosol particle mass analyser (APM) and the aerosol mass spectrometer (AMS). The latter being the most informative in terms of time resolved chemical composition with simultaneous particle size distribution. To measure certain particle properties it is necessary to perform sample collection with subsequent analysis by for instance electron microscopy, x-ray, PCR etc. There is a range of possibilities to measure a wide range of properties of airborne (nano)particles. However, due to instrumental limitations and cost effectivity it is often necessary to choose between simplicity and accuracy (or high time resolution and relevant particle characteristics). It is still also difficult to measure relevant exposure metrics such as only the engineered nanoparticles, but new methods are emerging. 3 Ekstrand-Hammarström B, Hong J, Davoodpour P, Sandholm K, Ekdahl KN, Bucht A, Nilsson B. Manuscript. 11 Effekter efter inandning av metalloxider i friska och känsliga individer Åsa Gustafsson, Forskningsingenjör PhD student, FOI Syftet med denna avhandling har varit att få en mer detaljerad förståelse av lungornas och immunsystemets påverkan efter inandning av nanopartiklar. En viktig del av arbetet har varit att skapa en förståelse om hur känsliga grupper i samhället påverkas av nanopartiklar. I detta arbete representeras speciellt känsliga individer av försöksdjur med inducerad allergisk luftvägsinflammation samt av djur med särskilt stor benägenhet att utveckla inflammatoriska sjukdomar. Dessa exponeringar är tänkta att efterlikna de som förekommer i arbetsmiljöer vid framställning av sådana nanomaterial. I denna avhandling har friska möss och råttor samt djur med en allergisk luftvägsinflammation andats in nanopartiklar av titandioxid eller järnoxid varefter de respiratoriska, inflammatoriska och immunologiska svaren studerats. Studierna visade att kroppen har svårt att göra sig av med titandioxidpartiklar som hamnar i lungblåsorna. Partiklarna inducerade en tidig ökning av celler i lungan redan efter 1 dag, och fortfarande efter tre månader kunde en förhöjd ökning av inflammatoriska celler observeras i lungblåsorna. Histologisk analys visade att det även fanns partiklar kvar i lungvävnaden. De djur som har en genetisk benägenhet för autoimmun-liknande sjukdomar utvecklade ett kraftigare immunologiskt svar efter partikelexponering jämfört med de djur som har medfödd benägenhet för allergiska sjukdomar. Djur med en allergisk luftvägsinflammation fick inga förvärrade andningsbesvär eller förvärrade inflammationer i lungan efter partikelexponering. Däremot var cellsammansättningen i lungan annorlunda jämfört med de allergiska djuren som inte fick partiklar. Dessutom påverkade tidpunkten för partikelexponeringen det inflammatoriska och immunologiska svaret i djuren beroende på om de ges vid allergensensibilisering eller senare då redan sensibiliserade djur utsätts för allergenet på nytt. Studien av järnoxidexponeringar visade att allergiska och friska möss som fick partiklarna i lungorna fick helt olika inflammatoriska svar. De friska mössen utvecklade en inflammation i lungan och i de lymfkörtlar som dränerar lungorna. Däremot observerade vi färre inflammatoriska celler hos möss med en pågående allergisk luftvägsinflammation en dag efter exponering för partiklar. Minskningen kunde även noteras i både luftvägar och lymfkörtlar. Cellminskningen kan bero på att lungor har förhöjda nivåer av fria syreradikaler vid pågående inflammation samt att järnoxid kan generera ytterligare reaktiva syreradikaler. Detta tillsammans kan leda till ökad oxidativ stress som i sig kan leda till celldöd. Studierna visade att titandioxidpartiklar ligger kvar i lungblåsorna under lång tid samt att en långvarig aktivering av immunsystemet kan uppstå vid lungexponering för nanopartiklar. En sådan immunaktivering skulle kunna leda till utveckling av immunmedierade sjukdomar. I råtta visades att nedärvda faktorer har betydelse för hur immunsystemet aktiveras efter inandning av titandioxidpartiklar. Allmäntillståndet hos allergiska möss försämrades efter titandioxidexponering men detta observerades inte i allergiska råttor. Däremot kunde en ökning av neutrofiler konstateras i möss och den råttstam som är benägen för autoimmuna sjukdomar. Den stora skillnaden mellan friska och allergiska djur vid lungexponering för nanopartiklar pekar på hur viktigt det är att inkludera känsliga individer vid hälsoriskbedömning av nanomaterial. 12 Nanosäkerhet ur ett EU- och OECD perspektiv Eva Hellsten, tidigare avdelningschef vid EU-kommissionen, vice ordf i OECD WPMN samt medverkan i svenska Nanoutredningen EU-kommissionen publicerade 2004 ”Towards an European Strategy for Nanotechnology” som framhöll nödvändigheten av att studera nanomaterialens miljö- och hälsoeffekter i samband med planerat utökat forsknings- och innovationsstöd till nanoteknologi via EU:s ramforskningsprogram. Året efter publicerades ”EU Action plan for Nanotechnology 20052009” som listar ett stort antal åtgärder inom forskning, etik, lagstiftning, internationellt samarbete etc. som EU-kommissionen och medlemsstaterna borde genomföra för att säkerställa en ”säker, integrerad och ansvarsfull” utveckling av nanoteknologi. Aktionsplanen slutredovisades av EU-kommissionen i en skrivelse 2009. Forskningssatsningarna har ökat radikalt i EU:s ramprogram sedan år 2000. Genom sjunde ramprogrammet har totalt flera miljarder Euro satsats. Vad gäller miljö- och hälsoforskningen ligger budgeten på cirka 25 miljoner Euro per år. Detta utgör mellan 5 och 10 % av den totala nano-budgeten (uppgifter från kommissionen varierar beroende på hur den totala nanoforskningen definieras inom ramprogrammen). Nano-området kräver långtgående samordning mellan olika politikområden. Inom EUkommissionen skapades en horisontell grupp med representanter från forskning, industri, miljö, konsumenthälsa och arbetsmiljö tidigt i processen för att koordinera åtgärder av olika slag, främst samordna lagstiftning med satsningar på forskning och kunskapsuppbyggnad om nano-säkerhet. Ett flertal medlemsländer har skapat statliga tvärgående organisationer för att säkerställa samordning på nationell nivå, inte minst när det gäller landets ställningstagande i olika nano-relevanta EU-frågor. EU-kommissionen har genomfört två översyner av lagstiftningen för nano-säkerhet (2008 respektive 2012). Kemikalielagstiftningen, Reach, är den viktigaste lagen för att se till att grundläggande information om potentiella risker tas fram. Dock krävs en anpassning av de metoder som används för ”vanliga” kemikalier till nanomaterial. Arbete med detta har därför pågått sedan ett antal år inom EU och internationellt. I arbetet har OECD en nyckelroll genom att länder världen över här enas om internationella standarder för testning inom kemikalieområdet. År 2006 etablerades OECD Working Party on Manufactured Nanomaterial (OECDWPMN) i vilket EU:s medlemsstater, EU-kommissionen, USA, Kanada, Australien, Japan, Korea m.fl. arbetar tillsammans för att se över hur testmetoder för kemikalier ska anpassas till att gälla även för nanomaterial. Även om lagstiftningen kan skilja sig åt mellan olika delar av världen bör de underliggande vetenskapliga testerna av farlighet inte ge olika resultat beroende på var i världen de är utförda. Det svenska regeringsuppdraget att utveckla nationell handlingsplan för nanosäkerhet samt säkerställa en god samordning av det nationella arbetet med nanosäkerhet redovisades i oktober 2013 (SOU 2013:70, www.regeringen.se ). Rapporten ger en bred översikt av området. Huvudförslagen innebär en ökad satsning på forskning om säkerhetsaspekter, ökade insatser inom EU och OECD samt en samordning av svenska myndigheter, forskare och intressenter genom bildandet av ett Nanoråd med ett operativt sekretariat, Nanocentrum. 13 Update on NM projects for the method, guidance and testing strategy development in the OECD Test Guidelines programme Jukka Ahtiainen, Senior researcher, OECD secretariat Historically the test guidelines have been developed and validated to be used for hazard identification and risk assessment of various chemicals. But are these test guidelines applicable for the regulatory testing of nanoforms of a substances or chemicals? In principle, most of the existing "endpoints" or more precisely measurement variables are applicable. However, the dosage of the test material and the characterization of the exposure need specific guidance in order to gain regulatory relevant data. The Guidance on sample preparation and dosimetry has been developed in the OECD (OECD 2012). As testing has to be adapted, and in a worst case for testing of each type of nanomaterial, will this challenge also the principle of MAD? The test conditions e.g. organic matter content during the test will affect the form and bioavailability of the nanomaterial, and detailed guidance is needed on the test conditions, Also, the conditions during the test should be documented carefully in order to achieve comparable and understandable results. The additional guidance for testing of nanomaterials with OECD test guidelines shall be seen as a refinement of the methods. This approach enables proper use of test guidelines and production of good quality data under the MAD principle for the regulatory purposes. The way forward Currently the harmonized guidance on testing the fate and effects of nanomaterials is being developed at various stages. New harmonized and validated OECD test guidelines are needed especially for the physical-chemical characterization (e.g. size, shape, surface chemistry and charge, zeta-potential) as well as for physic-chemical interactions (dissolution of ions and dispersion stability) of nanomaterials. This basic knowledge of the nanomaterial under assessment is crucial to guide further (eco)toxicity and fate testing – which tests in which compartment are relevant, but also to better understand and interpret the results. The basic reactions and transformations of the nanomaterial for example in aquatic media should be tested at various conditions e.g. pH, ion strength and organic matter content. Several OECD guidance documents are under development e.g. for aquatic toxicity testing (http://www.oecd.org/env/ehs/nanosafety). These comprise of decision frameworks based on the basic physical-chemical properties of the nanomaterial to be tested. One specific example in the environment fate testing is to develop technical guidance for dietary bioaccumulation of nanomaterials in fish using the OECD 305 test guideline. There are regulatory needs for harmonized guidance for testing the effects and fate of nanomaterials, however at the same time OECD is also developing guidance for grouping and categorization of nanomaterials. The grouping of nanomaterials will be based on their chemical composition including coatings, size, shape, basic physical-chemical reactions and biological effects. This will hopefully help to understand some basic mechanisms of the effects and provide possibilities for read-across interpretation between some nanomaterials. References OECD 2012 Guidance on sample preparation and dosimetry for the safety testing of manufactured nanomaterials. Series on the Safety of Manufactured Nanomaterials No. 36, OECD Paris, France 14 Nytt om nano från Kemikalieinspektionen Elin Simonsson, Kemikalieinspektionen Ändringar av bilagorna till EU:s kemikalieförordning Reach har planerats på att genomföras sedan 2013. Ändringarna är tänkta att anpassa informationskraven i bilagorna till nanomaterials speciella egenskaper. Arbetet har blivit ytterligare försenat och tidigaste tidpunkten för ett förslag från Europeiska kommissionen är nu satt till sommaren 2015. Diskussioner förs i en av Europeiska kommissionens expertgrupper (CASG Nano). En annan viktig fråga är Europeiska kommissionens rekommenderade definition som är avsedd att användas i lagstiftningssammanhang. Under 2014 har en översyn av definitionen pågått som förväntas bli färdig under 2015. Definitionen ska särskilt ses över med hänsyn till kravet på att minst 50 % av partiklarna ska vara inom nanoskalan (1-100 nanometer). Översynen är uppdelad i en vetenskaplig del och en policy del. Den vetenskapliga delen består av tre rapporter från Europeiska kommissionens vetenskapliga gren (JRC). Policydelen kommer bl.a. bestå av ett offentligt samråd där det kommer att vara möjligt lämna synpunkter på hur definitionen bör se ut. Den tredje frågan som är aktuell i EU just nu är Europeiska kommissionens konsekvensutredning om åtgärder för ökad transparens på marknaden. Den åtgärd som främst diskuteras är att eventuellt införa ett EU-register för nanomaterial. Kemikalieinspektionen har svarat på ett offentligt samråd i frågan. Konsekvensutredningen färdigställs under 2015 varpå Europeiska kommissionen kommer att avgöra om och vilka åtgärder de tänker vidta. Nanomaterial i kosmetiska produkter – vad har hänt sedan de nya reglerna infördes? Tomas Byström, Läkemedelsverket Reglerna för kosmetiska produkter har ändrats från att vara EU-direktiv som implementerades nationellt till att vara en direkt gällande EU-förordning. Förordning (EG) nr 1223/2009 om kosmetiska produkter trädde i kraft i slutet av 2009, men den tillämpades fullt ut först den 11 juli 2013. Bland de tydligaste nyheterna i EU-förordningen var särskilda regler för nanomaterial i kosmetiska produkter. Nanomaterial definieras som: ett olösligt eller biopersistent material som är avsiktligt tillverkat, med en eller fler yttre dimensioner, eller en inre struktur, med ett spann på mellan 1 och 100 nm. De regler som gäller för nanomaterial i kosmetiska produkter är: · · Varje användning av nanomaterial måste anmälas till EU-kommissionen 6 månader före produkter släpps ut på marknaden EU-kommissionen avgör från fall till fall om den anmälda användningen behöver granskas av en vetenskaplig kommitté Vissa ämneskategorier förhandsgranskade innan tillåtande (UV-filter, färgämnen, konserveringsmedel) Övriga nanomaterial granskas specifikt för den anmälda användningen, anmälan ska innehålla uppgifter om nanomaterialets egenskaper · Innehåll av nanomaterial måste framgå av innehållsförteckningen på förpackningen Exempel: Titanium Dioxide (nano) 15 Sedan reglerna för nanomaterial började tillämpas fullt ut har det inom EU anmälts cirka 25000 kosmetiska produkter med nanomaterial. Vanligaste kategorierna är solskyddsprodukter (7300 st.), sminkprodukter (7000 st.) och ansiktsprodukter (2700 st.). De anmälda ansiktsprodukterna är av allt att döma dagkrämer som innehåller UV-filter. Från tillverkare/importörer Sverige är cirka 150 produkter anmälda, varav 80 st. sminkprodukter och 60 st. solskyddsprodukter. Läkemedelsverket kan dock konstatera att flera aktörer som sätter solskyddsprodukter på marknaden inte anmält dessa på rätt sätt. Delar av det regulatoriska arbetet med nanomaterial har dock inte varit i tid. Rent formellt är de vanligaste nanomaterialen (Titanium dioxide, CI 77266) ännu inte tillåtna i nanoform. Detta delvis på grund av oklara definitioner av produkttyper som innebär inhalationsrisk (”spayprodukter”). EU-kommissionen skulle senast den 11 januari 2014 ha publicerat en katalog över de nanomaterial som används. Denna publicering har dock dröjt på grund av felaktiga anmälningar från företagen. Katalogen är sammanställd, och ska publiceras så snart den är översatt. Danske aktiviteter vedr. nanomaterialer Flemming Ingerslev, The Danish Environmental Protection Agency Nanomaterialer (NM) indgik i den danske kemikaliehandlingsplan fra 2010-2013, hvor fokus især var på at skabe overblik viden over de vigtigste nanomaterialer 4 samt at bidrage til EUarbejde med nanomaterialer 5. I den opfølgende kemikalieindsats (2014-2017) er der fokus på at sikre, at dansk viden om nanoteknologi bidrager til udviklingen af en fælles EU-løsning (http://kemikalieindsatsen.dk). Den ny danske regering vedtog i 2011 initiativet ”bedre styr på nano”, som har til formål at skabe øget klarhed over eksponeringsveje og konsekvenserne for forbrugere og miljø ved anvendelse af nanomaterialer. Den styrkede indsats på nanoområdet omfatter blandt andet udvikling af et nanoproduktregister. Der er i årene 2012-2015 afsat 6 millioner danske kroner til indsatsen. Samlet skal initiativet skabe overblik over situationen med hensyn miljø- og forbrugersikkerhed i forhold til nanomaterialer i Danmark. Initiativet omfatter således projekter som skal 1) skabe overblik over eksisterende viden vedr. nanomaterialers sundhedsegenskaber og deres miljøegenskaber, 2) bidrage til ny viden om nanomaterialers hudgennemtrængelighed og nanomaterialers opløselighedshastighed i miljøet, 3) undersøge udbredelsen, anvendelse og risici af konkrete nanoprodukter, samt 4) skabe generelt overblik over anvendelsen af nanomaterialer i Danmark. Et vigtigt element til at skabe overblik over nanomaterialer er det danske nanoproduktregister, som blev oprettet i juni 2014 i forbindelse med offentliggørelse af bekendtgørelsen om det danske nanoproduktregister (BEK nr 644 af 13/06/2014). Denne bekendtgørelse beskriver den registreringspligt som gælder alle virksomheder der sætter nanoprodukter på forbrugermarkedet i Danmark. Bekendtgørelsen omfatter således både producenter og importører af nanoprodukter. Nanoprodukter defineres som udgangspunkt som artikler eller kemiske blandinger, der indeholder nanomaterialer (jf. EU’s definition) og som frigiver disse nanomaterialer. Bekendtgørelsen undtager dog produkter, som reguleres under reglerne for fødevarer, fødevarekontaktmaterialer, medicinsk udstyr, kosmetik, pesticider og affald. 4 The Danish Environmental Protection Agency. Survey on basic knowledge about exposure and potential environmental and health risks for selected nanomaterials. Environmental Project 1370, 2011. 5 The Danish Environmental Protection Agency. Information Requirements for nanomaterials – IRNANO. Environmental Project 1469, 2013. 16 Endvidere undtager den produkter, hvor nanomaterialerne ikke bevidst er fremstillet i nanostørrelse og endelig undtager bekendtgørelsen visse konkrete produkttyper (bl.a. maling og gummiprodukter) med indhold af titandioksid, carbon black og silicium dioksid. Første indberetningsår slutter d. 30. august 2015. I Nanoproduktregisteret er der dels nogle tvungne informationskrav og dels nogle frivillige krav. De tvungne krav omfatter information om den indberettende virksomhed, om produktet, om nanomaterialets kemiske sammensætning og om det er registreret under REACH. Endvidere er det frivilligt at indberette en række oplysninger om selve nanomaterialet (blandt andet partikel størrelse, størrelsesfordeling, oplysninger om aggregering m.m.). De frivillige oplysninger svarer til dem, som OECD har vedtaget harmoniserede standard formater for (OHTs). Som hjælp til de virksomheder der skal indberette, har Miljøstyrelsen udarbejdet vejledninger på dansk og engelsk 6 7. Der er endvidere oprettet en help-desk og en FAQ-side, hvor virksomheder kan få svar på spørgsmål (http://mst.dk/virksomhedmyndighed/kemikalier/miljoestyrelsens-nanoindsats/). Nanocellulose and NANoREG- project Finnish Safety and Chemicals Agency The safety of nanomaterials is investigated in the EU’s just-beginning extensive NANoREG project as a joint effort by the authorities and the industry. Finland’s goal in the project is to continue to study the safety of microfibrillar and nanofibrillar cellulose. To date, only a little is known about the health and environmental hazard impacts of nanoparticles, although the industrial use of nanomaterials has increased rapidly. For example, they are already common in sports equipment, sunscreens and other cosmetics products. Nanotechnology is a technique for building nanometre-scale structures (one nanometre is one millionth of a millimetre). Interest in the use of nanoparticles is great, as they can be used to improve product characteristics; for example, nanoparticles help make a coat of paint more scratch-resistant. On the other hand, the safety of nanoparticles raises questions. It is difficult to identify risks, as matter can have an unknown behaviour in nanoscale. The effect on cellular level can also vary according to what impurities have attached to the nanoparticle or which substance has been purposefully used to coat it. The industrial use of nanomaterials has stirred up animated discussions in the EU. The REACH Regulation regulating the registration, evaluation, authorisation and restriction of chemicals plays a central role in legislation. The idea of safety-promoting dialogue between the industry and the authorities has come up to complement the idea of just using regulatory measures. This forms the basis of the NANoREG project to be implemented in the years 2013 to 2017. Authorities, research institutes and companies and consortiums from fourteen European countries will participate in NANoREG. The project aims at developing guidelines for safe usage risk management and safety instructions, while assessing the need for new legislation. 6 Miljøstyrelsen. Vejledning om indberetning til det danske nanoproduktregister. Vejledning fra Miljøstyrelsen nr. 5, 2014. 7 The Danish Environmental Protection Agency. Guideline for the Danish Inventory of Nanoproducts. Guidance from the Danish Environmental Protection Agency No. 5, 2014 17 A stable and safe operating environment is a benefit that is shared by both the authorities and the industry. It is necessary for new applications and innovations, and the resulting investments, to be possible in the first place. In Finland, participation in the NANoREG project is coordinated by the Finnish Safety and Chemicals Agency (Tukes) that is also responsible for oversight and guidance concerning the REACH regulation. Also included in the project are the Finnish Institute of Occupational Health, responsible for the experimental in vitro and in vivo studies, and Stora Enso and UPM as a joint Nordic Cellulosa consortium. Finland’s national research portion of the Nanoreg project focuses on microfibrillar and nanofibrillar cellulose materials that have several potential industrial applications in different products. Microcellulose and nanocellulose comprise wood fibre and fibre bundles originating from wood cellulose. The intention is to study the safety of biodegradable microcellulose and nanocellulose experimentally by means of biological testing. This is important in order for it to be possible to use nanocellulose, for example, as raw material for cosmetics, food additives or packaging. In the responsible development of products manufactured from micro and nanocellulose, research plays a key role. Research works aim to find and confirm potential benefits in microcellulose and assess the safety measures required for manufacturing and utilization of the materials. For this reason, the Nordic Cellulosa consortium acts in close cooperation with other fields and authorities, and promotes research in safe applications of microfibrillar and nanofibrillar cellulose. 18 2 Bilagor Bilaga 1. Deltagarlista Bioforsk Joner Erik Danmarks Tekniske Universitet Bloch Hartmann Nanna Cupi Denisa Europeiska kommissionen Hellsten Eva Finnish Institute of Occupational Health Stockmann Juvala Helene Hyytinen Eija-Riitta Einola Juha Finnish Safety and Chemicals Agency Palomäki Jaana Bucht Anders FOI Ekstrand-Hammarström Barbro Gustafsson Åsa Formas Vikström Anna Försvarets Materielverk Henningsson Kenth Ramfjord Birgit Westlund Robert Försvarsmakten Jalalian Nazli Generalläkaren Duf Jessica Kängström Marianne Andersson Yvonne Kemikalieinspektionen Anfält Lisa Gellerstedt Therese Hellmér Lena Moore Gregory Simonsson Elin Wendt - Rasch Lina Virefjord Tania Kommerskollegium Housset Cedric KTH Lazarevic David Livsmedelsverket Pihlström Tuija Svensson Kettil Löndahl Jakob Lund University Nilsson Annika Bohgard Mats 19 Byström Tomas Läkemedelsverket Hillgren Anna Salin Kia Hedlund Britta Naturvårdsverket Mattsson Cecilia Norwegian Institute for water research Macken Ailbhe Norwegian Environment Agency Andersen Sjur Gudbrandsen Marius OECD Secretariate Ahtiainen Jukka Regeringskansliet Tapper Sofia SINTEF Materials and Chemistry Roman Netzer Socialstyrelsen Domeij Helena The Danish Environmental Protection Agency Zenner Boisen Anne Mette Ingerslev Flemming Bengtsson Malena Trafikverket Reuithe Anna 20 Bilaga 2. Föreläsarnas power-point presentationer 21 Nanomaterials in a Life Cycle Perspective David Lazarevic [email protected] Division of Industrial Ecology Department of Sustainable Development, Environmental Science & Engineering KTH – Royal Institute of Technology • National action plan for the safe use and handling of nanomaterials (2013) • As part of this action plan: • Lazarevic and Finnveden, 2013. Life cycle aspects of nanomaterials. Environmental Strategies Research, KTH, Stockholm. (In English) • Finnveden and Lazarevic, 2013. Livscykelaspekter och nanomaterial. Avdelningen för miljöstrategisk analys, KTH, Stockholm. (In Swedish) • Liljenström, C., Lazarevic, D., & Finnveden, G. 2013. Silicon-based nanomaterials in a life-cycle perspective: including a case study on self-cleaning coatings. KTH, Stockholm. 2 Benefits and Risks of Nanomaterials “To some it represents the miracle cure for all that ails us. To others, it could be the end of the world as we know it” (Maynard, 2010). Potential Benefits • Expected significant impact on virtually all industrial sectors including healthcare, agrifood, transport, energy, materials, and ICT. • Potential areas • Monitoring • Remediation and pollution • Resource saving (energy) 3 Benefits and Risks of Nanomaterials Potential impacts • Toxicological risks to humans and the environment • Increase in the extraction of raw materials • Increase energy use during production phases • Higher material requirement (better specifications) • Increased waste production during production (hazardous waste) • End-of-life: what happens to waste products? 4 Nanomaterials in a Life cycle perspective The general consensus among scientists, researchers, and regulatory agencies is that the potential health and environmental risks of engineered nanomaterials (ENMs) should be evaluated over their entire life-cycle (Grieger et al. 2012). • • Life cycle Assessment Risk Assessment 5 Life Cycle Assessment • A Tool for assessing the potential environmental impacts associated with a product/service system by: o compiling an inventory of relevant inputs and outputs o evaluating potential impacts associated with inputs and outputs o interpreting results of inventory and impact assessment • LCA follows a cradle-tograve approach (Lazarevic & Finnveden, 2013) 6 Resources and materials Energy Components and semi -products Manufacture Use and maintenance Recycling and disposal Raw materials Process Waste Products Emissions LCA Phases • Goal and Scope Definition • Life Cycle Inventory (LCI) • Life Cycle Impact Assessment (LCIA) • Interpretation Hazardous waste Waste (volume) Land use Exotoxicity Human toxicity Eutrphoication Photochemical ozone formation Acidification Global Warming B A 0 20 40 60 80 100 120 7 Life Cycle Assessment • Enables the study and comparison of different options to supply a given function • Enables the identification of environmental ‘hotspots’ throughout the product/service life cycle • LCA attempts to be comprehensive with respect to the environmental interventions and environmental issues considered. 8 • LCA’s focus on the product/service system and RA’s focus on the emissions of a single substance • The results of LCA are comparative whereas the results of RA are absolute • LCA covers a range of environmental impacts whereas RA primarily cover toxicological and (eco)toxicological impacts. (Grieger et al. 2012) 9 Raw Materials Manufacturing Use E-O-L Babaizadeh and Hassan (2013): Comparison of TiO2 coated class with float glass Bauer et al. (2008) Greijer et al. (2011) Nanocrystaline dye sensitized solar cell (from nano-TiO2 and carbon black) Griffiths and O’Byrne (2013) MWCNT formation via catalytic chemical vapour deposition. Grubb and Bakshi (2011a, 2011b) Life cycle energy use of nano TiO2 production and e.g. steel, aluminium, polysilicon production Isaacs et al. (2010) Production of single wall carbon nanotubes Joshi (2008) Comparison of nanoclay composite biopolymer with biobased polymers Khanna et al. (2008) & Khanna and Bakshi (2009) polymer nanocomposites compared to steel, aluminum and PP Kushnir and Sandén (2008) Energy requirements for fullerene and nanotube synthesis Lloyd and Lave (2003) Clay polypropylene ENM's instead of steel or aluminum in vehicle body panels Lloyd et al. (2005) Nanofabrication technique of platinum group metal (PGM) particles in automotive catalysts Merugula et al. (2010) Comparison of Glass fibre reinforced plastics an vapour grown CNts for wind turbine blades Meyer et al. (2011) Socks with and without Ag ENM's Moign et al. (2010) Manufacturing of yttria-stabilized-zirconia ENM coating Osterwalder et al. (2006) Energy comparison of wet and dry synthesis methods for oxide nanoparticle production Roes et al. (2007) Comparison of polypropylene nanocomposite with conventional polypropylene Şengül and Theis (2011) LCA of quantum dot photovoltaic (QDPV) module compared to silicon and thin film PV’s Singh et al. (2008) SWCNT production Walser et al. (2011) Comparison of nanosilver t-shirts and conventional t-shirts Environmental impact categories Toxicological impact categories (non-nanoparticle release based) 10 Energy use Nanoparticle Toxicity impact (nanoparticle release based) Nanomaterials in a Life cycle perspective Incineration & Landfill Environmental Burden • Potentially energy intensive raw material extraction, processing, and nanomanufacturing processes • Potential depletion of non-renewable resources • Possible release of toxic emissions & unconventional liquid streams Extraction of Raw Materials Recovery Recycling Release of ENMs to the Environment End of life Reuse Production Release of ENMs to the Environment Distribution Use Missing Information • Impacts of raw material use on supply chains of other products • Potential release, fate and transport of ENMs • Performance of ENM products • Amount & characterisation of waste streams Uncertainties • Waste & emissions from ENM production • ENM exposure & toxicity • Preferred method of ENM disposal (Lazarevic & Finnveden, 2013) Engineered nanomaterial Product life cycle 11 Current use of LCA: Cradle to Gate CED for CNFs compared to aluminium, steel and polypropylene (Reproduced from Khanna et al. (2008)) 12 Current use of LCA: Cradle to Gate CED of polymer nanocomposites that provide equal stiffness to a steel component (Reproduced from Khanna and Bakshi (2009)) 13 Current use of LCA: Cradle to Use as part of a car, driving 280000 km (Reproduced from Hischier and Walser (2012)) 14 Current limitations of Applying LCA to nanomaterials CNF emissions and impacts not included Khanna et al. (2007) 15 Life Cycle Assessment of Nanomaterials Goal and Scope Definition • ENMs may have specific functions and material properties that provide additional gains when used as a substitute for traditional materials Life Cycle Inventory • Lack ENM specific data related to the outputs of the processes o Data on Input side, no data on output side o It is important to know if ENMs change their form during their life cycle, due to aging and other influences such as weather, mechanical stress/pressure, etc. • LCI databases do not distinguish between bulk materials and ENMs • Populating LCI databases with ENM specific information, such as size and shape, is of critical importance 16 Life Cycle Assessment of Nanomaterials Life Cycle Impact Assessment • • • • ENMs may exhibit unconventional behaviour, leading to unexpected fate, transport, and toxicity mechanisms in human and ecological systems A complete lack of characterization factors for release of nanoparticles indoors and outdoors LCIA methods such as CML 2001, Eco-Indicator 1999 or Impact 2002 do not cover toxicological effects of nanoparticles The current understanding of effect mechanisms, dose-response relationships, as well as transport and transformations in the environment may not be sufficient to ascertain a representative characterization of ENMs. 17 Conclusions • • • • LCA of nanomaterials is still in the very early stages Consideration of the impacts of ENMs in LCA is currently inadequate, due to: – Lack of data on nanomaterial production – Lack of data and uncertainties on what should be included in the LCI – Uncertainties on how to assess the impacts of ENMs (LCIA) Need for cooperation between the LCA community and the nanotoxicology community LCA needs to be complemented by RA to assess risk related to specific life cycle stages 18 References Greijer, H., Karlson, L., Lindquist, S.E., Hagfeldt, A., 2001. Environmental aspects of electricity generation from a nanocrystalline dye sensitized solar cell system. Renewable Energy 23, 27–39. Hischier, R., Walser, T., 2012. Life cycle assessment of engineered nanomaterials: State of the art and strategies to overcome existing gaps. Science of The Total Environment 425, 271–282. Khanna, V., Bakshi, B.R., 2009. Carbon nanofiber polymer composites: evaluation of life cycle energy use. Environmental Science & Technology 43, 2078–2084. Khanna, V., Bakshi, B.R., Lee, L.J., 2007. Life cycle energy analysis and environmental life cycle assessment of carbon nanofibers production, in: Electronics & the Environment, Proceedings of the 2007 IEEE International Symposium On. IEEE, pp. 128–133. Khanna, V., Bakshi, B.R., Lee, L.J., 2008. Carbon nanofiber production: Life Cycle Energy Consumption and Environmental Impact. Journal of Industrial Ecology 12, 394–410. Lazarevic, D. and Finnveden, G., 2013. Life cycle aspects of nanomaterials. Environmental Strategies Research, KTH, Stockholm. 19 Dermal absorption of nanomaterials Projects from the Danish EPA Anne Mette Boisen Chemicals Unit, Danish Environmental Protection Agency (EPA) Presentation outline  Introduction to the Danish Nano Initiative Better Control of Nano  Dermal absorption of nanomaterials – Literary project (conducted by IOM from UK)  Dermal absorption of nanomaterials – Eksperimental project (conducted by Aarhus University from DK) Better control of Nano initiative (24 mio. DKK in 2012-15): Dermal absorption –Literary project  Danish EPA Environmental Project No. 1504, 2013 Report and database Scientific assessment of available studies on dermal absorption Aims • assessment of the extent of absorption of nanomaterials; • identification of nano-specific characteristics that may influence the absorption of nanomaterials; • evaluation of which test method(s) would most closely simulate the transport of nanomaterials through human skin • candidates for testing and assessment of the specific research areas that require more knowledge. Search strategy Assessment of reliability and relevance of studies -Klimisch criteria and NM characterization (Card and Magnuson 2010) Results and recommendations  Absorption of NM into systemic circulation: Possible (small fraction) few robust, well performed studies, no clear guidelines (hard to compare/interpret)  Parameters: Size, surface chemistry (coating), shape Results and recommendations  Test methods: Harmonised testing approaches (specific technical guidance given in the report). Human golden standard (but ethics and cost)  Candidates for testing: Systematic test of priority candidate properties (size, surface chemistry)  Research gaps: Effect of flexed skin, follicular penetration, children, extending the study period Dermal absorption –Experimental project Project manager Christiane Beer, Aarhus University Started spring 2014 ends summer 2015 Overview • Candidates for testing: Nanomaterials used in sunscreen: Titanium dioxide and Zinc Oxide • Investigation of characteristics: Size and coating • Test methods: In vitro Epiderm model In vivo mouse inflammation model In vivo mouse xenograft model Candidates for testing  Titanium Dioxide Size: (TiO2, rutile, high purity 99.9%, 30 nm) (TiO2, rutile, high purity 99.9%, 100 nm) Coating: (TiO2, rutile, 30 nm) coated: Silicone Oil (hydrophobe) (TiO2, rutile, 30 nm) coated: Silicon and Aluminium (hydrophile) UV-Titan M 161: TiO2 nanoparticles, rutile, 17 nm, coated: Alumina, stearic acid UV-Titan M 262: TiO2 nanoparticles, rutile, ~20 nm, coated: Alumina, silicone  Zinc Oxide: Coating: (ZnO, high purity 99.95%, 18 nm, uncoated) (ZnO, 99+%, 20 nm, coated: 1 wt% Silane Coupling Agent) (hydrophile) Vehicle Wt% 61.90 % 0.20 % 0.10 % 1.00 % 2.00 % 2.00 % 10.00 % 2.80 % 4.00 % 3.00 % 3.00 % 10.00 % Trade name INCI Phase Water 1 Aqua Keltrol AP 1 Xanthan Gum Dermofeel PA-3 1 Sodium Phytate, Aqua, Alcohol Verstatil PC 1 Phenoxyethanol, Caprylyl Glycol Propylen Glycol 1 Propylene Glycol Glycerin 1 Glycerin Waglinol AB 1215 2 C12-C15 Alkyl Benzoate Parsol 340 2 Octocrylene Parsol MCX 2 Ethylhexyl Methoxycinnamate Parsol 1789 2 Butyl Methoxydibenzoylmethane Mulsifan RT 11 2 Ceteareth-22 Soldoc EB 29 2 Isostearyle Isostearate C12-C15 Alkyl Benzoate is used to pre-disperse nanoparticles before adding them to the sun cream. 2.5 wt% NP In vitro model in vitro EpiDerm™ system (MatTek) 3D in vitro skin model Analyses • • • • • • TEER (trans epithelial electric resistance) electron microscopy (TEM) Histology skin corrosion/irritation tests (MTT assay) ICP-MS Cytokine analysis of medium (11 cytokines by multiplex flow cytometer assay) Set-up Each sample will be treated with 30 μl of the test substances (All 8 NP are tested).  Day 1 – Arrival of the cells  Day 2 – TEER measurement Exposure to sunscreen +/- nanoparticles and untreated control for 20 hours  Day 3 – Washing of the EpiDerm models (Medium samples for ICP-MS and cytokine analysis)  Day 5 – Medium exchange (Medium samples for cytokine analysis)  Day 7 – TEER measurement Sample preparation for EM and histology Medium samples for cytokine analysis MTT assay skin irritation/skin corrosion In vivo Inflammation model  Acute irritant contact dermatitis model TPA: 12-O-tetradecanoylphorbol-13 acetate Induced: Erythema Oedema Scaling Epidermal hyperplasia Infiltrates of monocytes lymphocytes neutrophils IL-1b, TNFa, IL-6 0 hours 4 hours 8 hours 24 hours Set-up A = Untreated (no sun spray, no nanoparticles) B = Control sun screen C = NP1 : (TiO2, rutile, high purity 99.9%, 30 nm) D = NP2 : (TiO2, rutile, high purity 99.9%, 100 nm) E = NP3 : (TiO2, rutile, 30 nm coated with Silicone Oil ) F = NP4 : (TiO2, rutile, 30 nm Coated with Silicon and Aluminium ) Set-up Day 1 2 3 4 8 TPA treatment X X X Sun screen application X X X Ear thickness Ear thickness Ear thickness Ear thickness Ear thickness EM, histology and ICP-MS sample preparation Storage blood and organs 10 µl sun screen per cm2 2 x 3 mm biopsies are taken from each ear for TEM and histology; leftover from the ear is frozen and stored for ICP-MS In vivo xenograft transplantation model Human skin Mouse skin Transplantation Engraftment In vivo xenograft model  Vehicle and NP1-4 are applied on day 1, 2, and 3  (10 µl sun screen per cm2).  On day 8, mice are killed (4 days post last treatment with NPs):  A = Untreated (no sun screen, no nanoparticles)  B = vehicle control sun screen no NPs  C = NP1 : (TiO2, rutile, high purity 99.9%, 30 nm)  D = NP2 : (TiO2, rutile, high purity 99.9%, 100 nm)  E = NP3 : (TiO2, rutile, 30 nm coated with Silicone Oil )  F = NP4 : (TiO2, rutile, 30 nm coated with Silicon and Aluminium ) Analyses • ICP-MS • TEM • histology Expected Outcome Experimental project • Project report (summer 2015) • Articles in peer reviewed scientific journals (summer 2015) Acknowledgements Literary project  Dr. Craig Poland, Steve Hankin, Craig Poland, Sheona Read, Julia Varet, Gillian Carse, Steven M. Hankin, IOM, United Kingdom,  Frans M. Christensen, COWI Denmark.  Reference group: Maxine McCall, CSIRO, Australia,  Jesper Bo Nielsen, Southern University of Denmark. Experimental project  Christiane Beer, Herman Autrup , Karin Stenderup, Lars Iversen, Duncan Sutherland, Jing Wang, Jens Randel Nyengaard, Torben Sigsgaard, Jakob Bønløkke, Aarhus University, Denmark.  Reference group: Craig Poland, Steve Hankin, IOM, United Kingdom. Uptake of TiO2-nanoparticles in lung epithelial cells ER TiO2-nanoparticles Mitochondria TiO2-nanoparticles 30nm Nucleus Interactions of nanoparticles with organs protected by internal biological barriers Anders Bucht, Swedish Defence research Agency Division of CBRN Defence and Security Raman imaging measures polymorph and size specific NP uptake and distribution in living lung epithelial cells a) P25/R9 -10 y /m -5 0 10 2200 P25 w vib=144 150 cm-1 0 100 5 50 c) y /m -5 -5 0 5 10 R9 w vib=448 cm-1 b) Raman mapping performed within the rectangular area visualized in (a) of P25 anatase characterized Leakage into nucleus region by the Eg vibrational mode at 145 cm-1. 0 50 440 30 0 220 5 c) Raman mapping of rutile characterized by the Eg vibrational mode at 450 cm-1. Small, soft NP agglomerates (such as anatase ”P25”) penetrates membranes more easily than hard agglommerates (such as rutile) 10 -5 0 5 Ekstrand-Hammarström B, Akfur CM, Andersson PO, Lejon C, Österlund L and Bucht A. Human primary bronchial epithelial cells respond differently to titanium dioxide nanoparticles than the lung epithelial cell lines A549 and BEAS-2B. Nanotoxicology 2011. TiO2 induce oxidative stress and pro-inflammatory response in lung epithelial cells a) Optical micrograph of A549 cell exposed to 50/50 wt% mixture of P25/R9 TiO2 nanoparticles. 10 -10 120.000 x magnfication P25 NP ontop of nucleus 0 b) Nucleus 80.000 x magnification 10 x /m Andersson PO, Lejon C, Ekström Hammarström B, Akfur C, Bucht A and Österlund L. Polymorph- and size-dependent uptake and toxicity of TiO2 nanoparticles in living lung epithelial cells. Small 2011 Changed properties of TiO2 NPs in serum Intracellular Superoxide production IL-8 [pg ml-1] MCP-1 [pg ml-1] control 150  4 1254  19 A14 256  20* 1209  133 A60 411  59* 1076  48 R5 487  73* 1193  121 R9 424  25* 1414  383 P25 840  126** 2178  131** Sample Exposure of A549 cells for 24 h exposure to 50 g TiO2 nanoparticles. Andersson PO, Lejon C, Ekström Hammarström B, Akfur C, Bucht A and Österlund L. Polymorph- and size-dependent uptake and toxicity of TiO2 nanoparticles in living lung epithelial cells. Small 2011. From studies of lung cells we know that: • Nanoparticles can penetrate the cell membrane and nucleus, and the penetration depends on size and particle structure. Z-potencial -24mV • NPs can induce oxidative stress and inflammatory response in cells, and this response depends on type of particle, cell type and exposure conditions. Analaysis of blood coagulation in vitro From studies of blood coagulation we know that: • TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. • this is in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. Tubing loops coated with heparin. Freshly drawn human blood is added to the loop together with the test nanoparticles. Rotated at 37°C in a heat cabinet. Aliquots of blood are removed at different time points during incubation for analysis Bo Nilsson and colleagues at Uppsala University Overall conclusions Remaining issues • A corona of biomolecules will be formed around the NPs before meeting the epithelial cell layer. • Do the adaptive immune system recognize biomolecules bound to the NPs as foreign bodies, thereby providing a risk for autoimmune reaction? • The corona will influence translocation through the epithelial barrier and the subsequent systemic response. • In the blood circulation, nanoparticles may have an impact on coagulation cascade, as well as induce innate and adaptive immune responses. Contributors and Collaborators Swedish Defence Research Agency The Toxicology team Barbro Ekstrand-Hammarström Åsa Gustafsson Sofia Jonasson Elisabeth Wigenstam Linda Elfsmark Bo Koch Christine Akfur Mona Koch Lina Thors Lina Ågren Ulrika Bergström Raman spectroscopy at FOI Per-Ola Andersson Christian Lejon Linnea Ahlinder Collaborators Dep. of Respiratory Medicine and Allergy, Umeå University Thomas Sandström and Anders Blomberg Dep.of Engineering Sciences and solid phase physics, Uppsala University Lars Österlund and colleagues Dep. of Immunology, Genetics and Pathology, Uppsala University Bo Nilsson and colleagues [email protected] • Do NPs in complex with biomolecules penetrate the blood-brain-barrier in concentrations that may harm the brain? Research on Nanosafety in Three Competence Centres at Lund University Measurement Techniques for Airborne Nanoparticles METALUND, Medicine and Technology for Working Life and Society JAKOB LÖNDAHL nmC@LU, Nanometer Structure Consortium CAST, Consortium for Aerosol Science and Technology The Lund Aerosol Group – One laboratory, two departments Ergonomics and Aerosol Technology Mats Bohgard, Ville Berg, Anders Gudmundsson, Christina Isaxon, Jonas Jakobsson, Jakob Löndahl, Patrik Nilsson, Erik Nordin, Joakim Pagels, Jenny Rissler, Christian Svensson, Aneta Wierzbicka, et al. Nuclear Physics Erik Swietlicki, Birgitta Svenningsson, Adam Kristensson, Göran Frank, Emelie Hermansson, Erik Ahlberg, Johan Martinsson, Pontus Roldin, Moa Sporre, Axel Eriksson, Cerina Wittbom et al. CAST Nanoparticles: what should we measure? Physical properties Size Number / surface area / volume Surface structure Electrical charge Radioactivity Shape Avoid measuring background particles What we want to measure is not similar to what we are able to measure Chemical properties Chemical composition (metals, toxins, …) Solubility Biological activity (viruses) Nanoparticles: how could we measure? Particle surface area monitors They are only a small fraction of the air (by mass) Nanoparticles smaller than the wavelength of visible light Examples: miniDiSC, NanoTracer, AeroTrak, NSAM, Partector Advantages: small, cheap, easy to use, suitable for personal exposure, hith time resolution (seconds), lung deposited surface area (??) Disadvantages: total concentration (10-300 nm), limited precision Particle size distribution, SMPS (FMPS) DMA 3E+5 CPC dN/dlogDp (cm‐3) Particle surface area monitors 2E+5 Idle engine Transient driving 1E+5 0E+0 10 100 1000 Dry mobility diameter (nm) Advantages: precise, high time resolution (~1 min) Disadvantages: complex, expensive Particle size distribution, ELPI Particle mass (and surface area) distribution APM, aerosol particle mass analyzer Advantages: high time resolution (seconds), some size information, possibility to analyse particles afterwards Disadvantages: complicated, not ideal for nanoparticles, lower precision than SMPS Particle mass (and surface area) distribution APM, aerosol particle mass analyzer (10-18 grams) Effective density [gcm‐³] DMA APM CPC 1.20 Why? A way to assess surface area, mass and lung deposition Cigarette smoke 1.00 Waterpipe smoke Fitted density 0.80 10 100 Diameter [nm] 1000 Aerosol Mass Spectrometer Particle composition with high time and size resolution (30-1000 nm), but requires a dedicated operator Analysis of sampled nanoparticles Lung deposition measurements No online methods available to obtain many important particle characteristics. Analysis of sampled particles needed: • Particle shape: electron microscopy (TEM, SEM) • Detailed chemical composition: e.g. x-ray, MS • Toxicity: in vivo (animals, humans) or in vitro (cell culture) • Biological properties: e.g. PCR Deposition Fraction Lung deposition measurements 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0.001 Total Extrathoracic Summary Biological analysis PCR, proteomics, biomarkers… Slow Tracheobronchial Alveolar Particle mass TEOM, gravimetric… 0.01 0.1 1 Particle diameter [µm] 10 100 Fast Particle number and surface area CPC, electrostatic… Cheap Simple (Unspecific) Summary • Possibilities to measure a wide range of properties of airborne (nano)particles • Sometimes a choice between simplicity and accuracy (or high time resolution and relevant particle characteristics) • Difficult to measure relevant exposure: - background particles vs produced particles - appropriate health metric unclear • New methods are emerging… Chemical analysis x-ray (PIXE, XRF, MAX-lab…), MS… Particle shape Electron microscopy, APM Particle size distribution (SMPS, ELPI, FMPS…) AMS, particle size and chemistry Expensive Complex (Specific) Background Nanomaterial Respiratory and immunological effects following inhalation of engineered nanoparticles Åsa Gustafsson Åsa Gustafsson Particle properties Studied effects Agglomeration Concentration Material composition Cytokines and chemokines in Lung lavage and in blood Shape NP Lung function Size Size distribution Surface charge, ζ-potential Cells in lung lavage and in lymph nodes Surface functionality Åsa Gustafsson Åsa Gustafsson How are susceptible individuals affected? Gustafsson et al (2011) J Immunotoxicol Study I Inflammatory and immunological responses in the airways following one exposure to titanium dioxide. Genetics Åsa Gustafsson • • • • • In vivo, Rat Administration Dose Particle size Analysis      Åsa Gustafsson Dark Aguoti Intratracheal 5 mg/kg body weight 200 nm and 2 µm 1, 2, 8, 16, 30 and 90 days following exposure Gustafsson et al (2011) J Immunotoxicol Gustafsson et al (2011) J Immunotoxicol I. Innate and adaptive immune system Nanoparticle 30 90 days after exp. Alveolar macrophages Lung epithelial cells Pro-inflammatory cytokines IL-1β, IL-10, IFN-γ, TNF-α, IL-8 Lymph nodes Pro-inflammatory cytokines IL-1β, IL-6, GM-CSF, TNF-α etc. 250 Neutrophils Neutrofiler ** 200 4 16 Antal celler (x10 ) (x104) Number of cells 8 Number Antal celler of cells (x104) (x104) Instillation 0 1 2 150 ** 100 ** 50 0 0 1 ** ** 2 # 8 16 30 17.5 Lymphocytes Lymfocyter 12.5 ** 10.0 90 90 (C) 7.5 ** 5.0 ## 2.5 0.0 0 Dagar efter instillering Days after exposure Dendritic cell ** 15.0 1 2 8 16 30 90 90 (C) Dagar efterexposure instillering Days after Lymphocyte - activation Åsa Gustafsson Åsa Gustafsson Gustafsson et al (2011) J Immunotoxicol Gustafsson et al (2011) J Immunotoxicol I. Titanium dioxide particles in lungtissue I. Cell differentiation TNF-α, IL-6, IL-1, GM-CSF, IL-8 Neu M1 TH1 IFN- GM-CSF TH1: Virus and bacteria TH2: Parasites IL-4, IL-10, IL-13 Neu: Neutrophil IL-6 IL-4 GCS-F IL-12 IL-10 TH17: Bacteria and fungal TH2 IL-13 IL-7 TH9: Reglation of parasites? TNF-α IL-5 IL-2 M2 IL-17 TREG IL-4, IL-5, IL-13 IL-1 20x 10x 40x IL-18 IL-9 TH9 TREG: T-regulatory lymphocyte M1: Macrophage type 1 – Virus and bacteria 100x TH17 M2: Macrophage type 2 - Parasite 100x 2 days IL-17, IL-6 Åsa Gustafsson Jonasson et al (2013) Inhal Toxicol II. Allergy schedule Study II Responses on the immune system and lung function following exposure to titanium dioxide in mice at different time points during the developement of allergic airway inflammation. In vivo Nanomaterial Particle administration Number of exposures Deposition, each exposure Dose, each exposure Allergen Åsa Gustafsson 90 days Åsa Gustafsson Jonasson et al (2013) Inhal Toxicol • • • • • • • 64x 30 days        Mice Balb/c TiO2 Aerosol 8 times á 2h 32±1 µg 1.5-1.8 mg/kg body weight Ovalbumin OVA Immunisation of allergen Allergen provocation Immunized OVA group OVA allergen 1. Allergen specific IgE antibodies 3. Airway reactivity OVA allergen 2. 4. Eosinophil inflammation TH2 immune activation IL-4, IL-5, IL-13 Åsa Gustafsson 2015-03-10 Jonasson et al (2013) Inhal Toxicol Jonasson et al (2013) Inhal Toxicol II. OVA-specific antibodies Airway inflammation II. Allergy schedule-Particle exposure OVA TiO2 Immunisation of allergen Allergen provocation Immunized OVA group Åsa Gustafsson 4 2 G r. 3 G r. 1 0 G r. 2 2 3 G r. r. 1 0 *** 6 O VA 20 Neutrophils Neutrofiler 8 ko nt ro ll *** G .3 Gr .1 .2 Gr Gr ll nt ro ko O VA 0.0 Immunized TiO2/OVA (gr. 3) *** *** G r. 1.0 0.5 *** 40 ll O.D * *** O VA *** 1.5 Immunized TiO2/OVA (gr. 2) Eosinophils Eosinofiler 60 nt ro 2.0 5 Number cells in BALF Antalof celler i BAL (x105) (x10 ) 2. Airway inflammation 1. OVA specific IgE antibodies Immunized TiO2/OVA (gr. 1) ko OVA allergen 5 Number cells in BALF Antalof celler i BAL (x105) (x10 ) OVA allergen Åsa Gustafsson Jonasson et al (2013) Inhal Toxicol Gustafsson et al (2014) Toxicol Study III II. Airway reactivity and TH2 immune activation Genetic influence on immunologic responses and lung physiology following exposure to titanium dioxide. 4. TH2 immune activation (IL-4, IL-5, IL-13) pg/ml in BAL 4 2 ** *** * * *** ********* *** IL -4 r. 3 r. 2 Gr. 1 Gr. 2 Gr. 3 *** *** 2500 2000 1500 1000 500 0 *** G G G r. 1 O VA 0 Kontroll OVA 25000 20000 15000 10000 5000 IL -1 3 * ** IL -5 6 ko nt ro ll RRS (cmH2Os/ml) 3. Airway reactivity • In vivo, Rat • • • • • • Nanomaterial Particle administration Number of exposures Deposition, each exposure Dose each exposure Allergen Åsa Gustafsson  Dark Aguoti (DA) Brown Norwegian (BN)  TiO2  Aerosol  10 times á 2h  160-170 µg  0.64-0.8 mg/kg body weight  Ovalbumin Åsa Gustafsson Gustafsson et al (2014) Toxicol Gustafsson et al (2014) Toxicol III. Allergen specific antibodies Airway inflammation Immunisation of allergen Immunized TiO2/OVA III. Airway reactivity Allergen provocation DA. Central airways Åsa Gustafsson 0.4 Kontroll n=8 OVA n=7 TiO2+ OVA n=7 *** 0.3 0.2 0.1 G (cmH2Os×mL-1) RRS (cmH2Os×mL-1) * 3 A A V 2 /O O O V A K on t ro ll 2 /O 0.00 Ti Ti O O V V A 0.0 0.5 0.0 Saline 5 2.25 2.00 1.75 1.50 1.25 1.00 0.75 0.50 0.25 0.00 Kontroll n=8 OVA n=7 OVA+TiO2 n=7 ** Saline MCh (mg×mL -1) 5 MCh (mg×mL -1) * *** Eosinofiler Neutrofiler Lymfocyter 3 * 2 0.1 1.25 TiO2/OVA PBS OVA 1.50 1.00 1.25 0.75 1.00 0.50 0.75 * 0.25 * 0.50 * 0.00 * Eosinofiler Neutrofiler Lymfocyter Neutrophils Lymphocytes 0.25 Eosinophils ** 2 0.2 K on t ro ll O.D 0.3 TiO2/OVA OVA DA Råtta * 1 DA rat BN rat 0.6 DARåtta Rat DA Control Kontroll 1.50 1 0.4 DA. Small airways 2. Airway inflammation OVA specific IgE antibodies Antal celler (x106(x10 ) 6) Number of cells in6BALF Antal celler (x10 ) 1. Åsa Gustafsson 3 Gustafsson et al (2014) Toxicol Gustafsson et al. Manuskript III. Mediators in healthy DA rats after titanium dioxid exposures Immunologic responses in airways and lymph nodes following inhalation to iron oxide (hematite) in healthy and in mice with allergic airway inflammation. IL-6 Healthy (control) 50 VEGF Healthy (TiO2) 25 000 40 50 40 30 15 000 125 100 10 000 100 80 75 25 10 30 40 50 10 30 20 3 000 20 25 20 IL-13 20 40 50 40 • • • • • • GM-CSF T H2 10 20 40 60 T H1 30 20 5 000 10 50 Proinflammatoric GCS-F 20 000 IL-7 Study IV T- , B-cell mature 6 000 9 000 50 12 000 15 000 Cardiovascular MIP-3α 75 60 80 IFN-γ 100 100 125 In vivo, Mice Nanomaterial Particle administration Dose Analysis Allergen • • • • • • Balb/c Iron oxide (Hematite) Intratracheally 5 mg/kg body weight 1, 2, och 7 days after exposure Ovalbumin IL-12 (p70) IL-18 Åsa Gustafsson Åsa Gustafsson IV. Cellular reduction i mice with an allergic airway inflammation IV. Inflammation in healthy mice 0.1 0.0 *** 0.15 0.10 0.05 0.00 Day 1 Day 2 Day 7 Number of cells (x106) Number of cells (x106) p=0.09 ** 0.015 ** 0.010 0.005 0.000 Day 1 Day 2 Day 2 Day 7 0.10 0.05 Day 1 0.04 0.03 *** 0.01 0.00 Day 7 ** 0.02 p=0.08 6 4 2 Åsa Gustafsson IV. Production of oxygen species Day 2 Day 7 Day 1 Day 2 Day 7 Eosinophils Macrophages * 1.0 0.5 Day 7 8 0 Day 1 Day 2 Eosinophils 0.05 1.5 0.0 0.00 Lymphocytes Eosinophils 0.020 Day 1 0.15 Number of cells (x106) 0.2 Hematite Hematit Neutrophils p=0.06 Number of cells (x106) 0.3 Vehicle Vehikel Macrophages 0.20 Number of cells (x106) 0.4 Hematit Hematite Number of cells (x106) Number of cells (x106) * Number of cells (x106) Vehikel Vehicle Neutrophils 0.5 Day 1 Day 2 Day 7 Lymphocytes 2.0 * 1.5 1.0 0.5 0.0 Day 1 Day 2 Day 7 Åsa Gustafsson Conclusions  TiO2-particles that are deposited in the alveolar region may remain over a long period of time (Study I and III).  TiO2-particles induce a long term activation of the innate- and adaptive immune system (Study I and III).  Inhalation of TiO2-particles before and during allergen provocation in immunized mice induced a neutrophil inflammation, body weight reduction and impaired general condition (Study II).  Inhalation of TiO2-particles does not exacerbate characteristics of alleric airway inflammation in rat, although there is a genetic variety regarding cellular composition (Study III).  Rats with inhereted predisposition towards developement of TH1 immune responses was more sensitive and expressed more mediators (Study III).  The cellular response in a lung with established allergic airway inflammation and associated draining lymph nodes does probably induce cell death following exposure to hematite NPs (Study IV). Åsa Gustafsson  It is important to include sensitive individuals when evaluating risk assessments of nanomaterials. Åsa Gustafsson Förväntad tillväxt i världen år 2000-2020 2020 – marknadsvärde 3 000 miljarder $ Nanosäkerhet ur ett EU- och OECD perspektiv Erfarenheter från EU-kommissionen, OECD och svenska regeringsuppdraget om nanosäkerhet KemI myndighetsmöte, 27 November 2014 Eva Hellsten Årlig tillväxt 2000 – 2008 ekonomi, sysselsättning, patent, vetenskapliga publikationer, investering i R&D ~ 20-35 % År 2000 – marknadsvärde 30 miljoner $ Adapted from M. Rocco et al 2011 EU Kommissionen år 2004… ”….Overall spending on R&D should be increased in Europe to balance the heavy investments that have been initiated by our main competitors” “….Any negative impact on public health, safety or the environment must be addressed upfront and as an integral part of technological development” “Towards a European Strategy for Nanotechnology, 2004” EU:s Aktionsplan 2005-2009 R&D finansiering av Nanotech från EU FP5 1998-2002 FP6 2002-2006 FP7 2007-2014  50-tal åtgärder som Kommissionen och medlemsländerna skulle genomföra för att säkerställa en “säker, integrerad och ansvarsfull” utveckling av nanoteknologi  Helhetsgrepp om forskning & innovation, industriell utveckling, etik, kunskapsuppbyggnad och lagstiftning för skydd av miljö och hälsa, internationellt samarbete etc.  Antogs inom EU 2005 280 miljoner € 1,4 miljarder € > flera miljarder € (?) Satsningen på miljö och hälsa har under åren ökat till dagens nivå på cirka 25 miljoner € per år “Nanosafety” som ett integrerat policy område Forskning och Innovation Inom EU kommissionen….. samordning mellan generaldirektoraten DG ENV Nano safety forskning Koordinering DG RTD DG ENTR DG INFSO DG SANCO Kommunikation Lagstiftning för nanomateria l DG EMPL Nano och REACH – en kapplöpning i tiden 2002 Nanotech R&D ökar i EU forskning 2003 REACH antas i EU Kommissionen (ton-gräns för registrering) 2004 ”Towards”-strategin 2005 ”Action Plan 2005-2009” 2006 REACH-lagstiftningen antas av EU Parlamentet och Rådet Vetenskapliga frågeställningar om nano och REACH Flertalet lagstiftningar för nanomaterial Kemikalier – REACH, Biocider, Pesticider Arbetsmiljö Konsument produkter – Läkemedel, Livsmedel, Kosmetika m.m. Miljö– Luft, Vatten, Avfall m.m. EU Kommissionens översyn av EU lagstifning 2008 resp 2012 EU:s Rekommendation av en definition för nanomaterial 2011 Risk-bedömning och nanomaterial Hazards Nya och/eller modifierade testmetoder och guidelines Validering Metoder av testmetoder. (eco)toxicity tests fate, transport characterization, standards, reference materials, metrics, dosimetry, validation Exposures exposure assessment Scientific uncertainty för att mäta och bedöma exponering Risk assessment Precautionary principle Proportionality principle Risk management Testmetoder Internationell samordning och harmonisering In vitro test Test Guidelines Databas OECD Working Party on Manufactured Nanomaterials (WPMN) – utveckla internationellt harmoniserade test metoder och test guidelines att användas i lagstiftning Exponerings ana lys OECD WPMN start 2006 Risk assesment Forskning – skapa internationella standards, nomenklatur, mät- och analytiska metoder ISO Livscykel analys Lagstiftning Samordning i medlemsländerna Myndigheter Forskare Industri NGO Central koordinering genom myndigheter & departement: Tyskland UK Nederländerna Jfr USA där NNI koordinerar Huvudförslagen – i linje med vad som görs inom EU och andra medlemsstater Satsning på forskning för att öka kunskap om miljö och hälsoeffekter I ett livscykelperspektiv. Anpassning av lagstiftning och testmetoder genom att förstärka arbetet inom EU och OECD Bygga upp ett Nanoråd och Nanocentrum för att bättre koordinera svenska insatser Sverige 2012 – regeringsuppdrag om nanosäkerhet  Utveckla nationell handlingsplan. Säkerställa en god samordning av arbetet med nanosäkerhet  Redovisades I oktober 2013. SOU 2013:70, www.regeringen.se  Remissrunda under våren 2014 med ca 70 svar OECD‐arbetet för nanomaterialsäkerhet idag – Innehåll: Ahtiainen Jukka | 27.6.2013 Myndighetsmöte  Nanomaterials upptag och spridning i kroppen och miljön  • OECD‐arbetet för nanomaterialsäkerhet idag • Jukka Ahtiainen, senior forskare, PhD OECD Sekretariat och Säkerhets‐ och kemikalieverket (Tukes)   • • OECD Working Party on Manufactured Nanomaterials (WPMN) Säkerhetsbedömning och testning Testmetodernas lämplighet Riskhantering I arbetsmiljön • • • OECD testmetoder (TG) och nanomaterialer Test Guidelines (TG) utveckling och WNT TG tillämplighet att testa nanomateraler or behov för nya metoder och riktlinjer (OECD GD) t.ex. testningstrategi • • Idag viktiga OECD projekten Fysikalisk‐ kemisk‐ egenskaper Miljöspridning och akkumulering Ekotoksisitet Hälsoeffekter (med toksikokinetik) • • • • Slutsatser och sammanfatning 27.11.2014, Kemi myndighetsmöte‐ Jukka Ahtiainen  OECD Working Party on Manufactured Nanomaterials (WPMN)  OECD Working Party on Manufactured Nanomaterials (WPMN) ‐ Vad har gjort hittills? Working Party on Manufactured Nanomaterials (WPMN) under OECD:s  kemikaliekomitteen var inträttade i September 2006 med uppgiften att verka för  internationell samverkan om hälso‐ och miljöriskrelaterade frågor när det gäller avsiktligt  tillverkade nanomaterialer.   För detta ändamål har ett antal styrgrupper bildats under WPMN  Systematisk analysering av resultat från “Sponsorship Programme” har börjat befintlig forskning (SG1 och SG3),  testar globalt och systematiskt givna representativa nanomaterialgrupper (SG3),  bedömer och förbättrar kemikalieprovningsmetodernas tillämpbarhet (SG4 och SG7) och    Guidance on sample preparation and dosimetry for the safety testing of manufactured nanomaterials (2012) I vilka man samlar information om:     Publikationer och riktlinjer för testning: uppgör anvisningar för riskbedömning och riskhanering (SG6 och SG8). redan 2012 och det andra projektet (phase 2) för verklig risk bedömning skall börjas snart (linken till EU projekten NANoREG som startade 2013).  Några riktlinjer och metoder måste förbättras, men i allmänhet test metoder och riktlinjer för kemikalier kan följas http://www.OECD.org/env/chemicalsafetyandbiosafety/safetyofmanufacturednanomaterials/ Varför måste OECD testmetoder utnytjas?   OECD test  guideline Good  Laboratory  Practise Mutual  Acceptance  of data For testing intrinsic properties  of chemicals (substances) Binding OECD countries and selected non‐members ►Avoids duplication of testing ►Reduces use of animals ►160 million euros saved each year (2010) ►“easily” adopted to EU  regulation (440/2008) for EU  regulatory needs 27.11.2014, Kemi myndighetsmöte, Jukka Ahtiainen Stakeholders (authority, NGO,  industry, academia) initiative TG proposal (SPSF) by MC Expert Group National Coordinators of the test  guideline programme (WNT) Commenting rounds Validation  package Draft  TGs OECD  secretariat Final approval by WNT at the meeting or written  procedure Joint Meeting , policy level and publication  Ahtiainen et al 2009/SETAc Göteborg 27.9.2012 | Nordisk råds Miljö‐och naturesursutvalg, Ahtiainen Jukka 3/9/2015 27.11.2014 Kemi myndighetsmöte, Ahtiainen Jukka OECD‐metoders tillämplighet att testa nanomaterialer (NM)  Biologiska “endpoints” (vad man observerar) är relevanta och tillämpliga OECD Test Guideline Programme – Hur att handla nya nanospesifika riklinjer och instrukrioner för NM testning  för NM testing till ex:       Number of offspring in reproduction tests‐ hur många babysar If the guidance given in the separate GDs can be seen as refinement of  Or should the NM specific guidance be inserted as annex in the TG? Bioaccumulation into tissues‐ akkumulering och spridning i kroppen the test guideline, should the result be still under MAD? CO2 production in biodegradation test‐ biologisk nedbrytning  Many apical and other endpoints in mammal tests‐ inflammationer Några nya “nanorelevant” Phys‐Chem‐ metoder behövs Guidance for similar matrices and test or for nanomaterial groups? Metals Metal CNTs Fullerenes NFC NCC oxides Soil tests Dosing and dosimetry of the test material and NM detection and Sediment tests characterization very important – Riktlinjer måste utveklas  TG development and guidance documents (GDs) and MAD  Aquatic tests Med harmoniserade riktlinjer oh metoder MAD‐principen torde hållas Bioaccumulation Degradation MAD = Mutual Acceptance of Data 27.11.2014 Kemi myndihetsmöte, Jukka Ahtiainen  27.11.2014 Kemi myndighetsmöte, Jukka Ahtiainen  OECD Test Guideline Programme – Hur att handla nya nanospesifika riklinjer och instrukrioner för NM  testning  Inhalation toxicity testing as an example  Minor changes in Test Guidelines  More extensive revisions in Guidance Documents (e.g. GD 29)  New Guidance Document for NM testing  Guidance for similar tests or for nanomaterial groups? Metals Metal oxides CNTs Fullerenes NFC Current  OECD guidance on  NM testing  Preliminary review of OECD test guidelines for their applicability to manufactured nanomaterials (2009)  Guidance manual for the testing of manufactured nanomaterials: OECD sponsorship programme – rev1(2009)  Guidance on sample preparation and dosimetry for the safety testing of NCC manufactured nanomaterials revision published 2012 Inhalation tox Oral tox  Dispersion protocols for in vitro testing (on-going work) Genotox  Development of integrated testing strategy for NM testing (started) Immunotox In vitro 27.11.2014 Kemi myndighetsmöte, Jukka Ahtiainen  OECD Horizontala mötena för detta (WNT &  WPMN) OECD metoder och instruktioner – phys‐chem characterization methods Aims: Review in terms of • …the need to amend existing or develop new OECD Test guidelines, …the need to develop specific Guidance for the testing of NM … identification of knowledge gaps regarding regulatory need Topic Venue The Hague, NL Inhalation Toxicology Environmental Fate and Ecotoxicology Berlin, DE Date 19‐20 October 2011 Physical‐Chemical Properties Querétaro, MEX Genotoxicity Ottawa, CAN 19‐21 November 2013 Toxicokinetics Seoul, COR 26‐28 February 2014 Physical‐Chemical Parameters:  Measurements and Methods Washington DC, USA 18‐19 June 2014 Categorization Washington DC, USA 17‐19 September 2014 26.11.2014, Nordic Nano WS‐ Jukka Ahtiainen  • 29‐31 January 2013 28 February – 01 March 2013 • The phys‐chem data is crucial for substance ID, to guide further testing and understand the results • Overlaps partly to env.fate methods (e.g. dissolution) • Reliable methods (MAD?) will enable triggering or waiwing of some testing‐ verkligen viktiga och nyttiga och behövs snart! Proposed methods Size, form, fiber rigidity, surface charge, zeta‐potential, surface chemistry… • Approved list of WPMN‐ men skulle vara på WNT listan! • Current status Not any included in the WNT project list! Cooperation with ISO TC 229 – samarbetet borde förbättras! • • 27.11.2014, Kemi myndighetsmöte‐ Jukka Ahtiainen  OECD‐ metoder och instruktioner– ecotoxicity and environmental fate methods OECD metoder och instruktioner– ecotoxicity and environmental fate methods TG: dissolution rate of nanomaterials in the aquatic environment Lead: US (US Army Corp) in cooperation with DTU TG: agglomeration behaviour of nanomaterials in different aquatic media Lead: GER (UBA), contracted to University of Vienna GD: agglomeration and dissolution of nanomaterials in aquatic media – decision tree GD: Assessing the Apparent Accumulation Potential of Nanomaterials Lead: UK (Uni Plymouth) with ES, NL, DE, FI TG: Nanomaterial Removal from Wastewater Lead: US (EPA) GD: Leaching in soil column  Cooperation: CAN (ENV CAN), US (EPA), GER (UBA) Lead: GER (UBA), contracted to University of Vienna GD Aquatic (and Sediment) Toxicology Testing of Nanomaterials Lead: US (US Army Corp) and UK (Uni Plymoth & Heriot‐Watt ‐ Alt dessa är viktiga, men mera behövs till ex. för jordtestning 27.11.2014, Kemi myndighetsmöte‐ Jukka Ahtiainen  27.11.2014, Kemi myndighetsmöte‐ Jukka Ahtiainen  Current OECD activities – ecotoxicity and environmental fate methods Current OECD activities – ecotoxicity and environmental fate methods GD: agglomeration and dissolution  of nanomaterials in aquatic media – decision tree GD: agglomeration and dissolution  of nanomaterials in aquatic media – decision tree • Lead: Germany (UBA); contracted to University of Vienna with EC,  DTU(DK) • Should support decision making regarding environment fate&  behaviour test performance/test strategy e.g. Identification whether nanospecific test is needed, • First information on mobility or possible  target compartments • Same timeframe like TG on agglomeration behaviour 26.11.2014, Nordic Nano WS‐ Jukka Ahtiainen  26.11.2014, Nordic Nano WS‐ Jukka Ahtiainen  Current OECD activities – ecotoxicity and environmental fate methods Current OECD activities – ecotoxicity and environmental fate methods GD Aquatic (and Sediment) Toxicology Testing of Nanomaterials GD Aquatic (and Sediment) Toxicology Testing of Nanomaterials 26.11.2014, Nordic Nano WS‐ Jukka Ahtiainen  26.11.2014, Nordic Nano WS‐ Jukka Ahtiainen  Current OECD activities – ecotoxicity and environmental fate methods GD Aquatic (and Sediment) Toxicology Testing of Nanomaterials 26.11.2014, Nordic Nano WS‐ Jukka Ahtiainen  Current OECD activities – human health Current OECD activities – ecotoxicity and environmental fate methods GD: Guidance on Fish Dietary Accumulation Studies for Engineered  Nanomaterials (content) • Introduction • scope of the guidance,  • limitations of TG 305,  • Bioaccumulation/ digestability • kinetics with nanomaterials…) • Decision tree and triggers for needing to do the test • Fate indications • In vitro digestability • Mixing into food • Practical in vivo testing: • Test designs, verification of exposure, detection and analytics • Calculations and interpretations of the results • Use in the risk assessment • Not BCF or BMF as such but useful information 26.11.2014, Nordic Nano WS‐ Jukka Ahtiainen  Current OECD activities – human health GD: Guidance on nanomaterial inhalation testing Guidances on nanomaterial genotoxicity testing  Project approved into the WNT work programme:  “Amendments to the Inhalation TGs and GD to Accommodate Nanomaterial Safety Testing (lead: US and NL)  Expertise to be broadened to WNT experts 26.11.2014, Nordic Nano WS‐ Jukka Ahtiainen  OECD‐ arbetet för nano‐säkerhet idag‐ slutsatser och sammanfattning   Mera phys‐chem‐metoder (OECD TGs) behövs  Många instruktioner (guidance documents, GDs) måste  utvecklas för att testa NM med OECD metoder  Alt detta menar att ECHA och dess instruktioner (ECHA  guidance for registration and fulfilling the information requirements) spelar mycket viktig roll Tusen tack‐ några frågor? 27.11.2014, Kemi myndighetsdag‐ Jukka Ahtiainen   Not yet included in the WNT work programme  OECD Workshop in Canada 2013‐ report available late  2014  Modifications of 487 (In vitro Micronucleus Test to accommodate NMs)  Comet assay  Not to use bacterial assays 26.11.2014, Nordic Nano WS‐ Jukka Ahtiainen  Ändringar av bilagorna till EU:s kemikalieförordning Reach Nanomaterial - en uppdatering om KemI:s arbete Elin Simonsson, Stockholm 27 november 2014 Översyn av kommissionens rekommenderade definition • Definitionen ses över särskilt med hänsyn till kravet på att minst 50 % av partiklarna ska vara inom nanoskalan (1-100 nm). • Kommissionens arbete med bilagorna blir ytterligare försenade. • Tidigare utlovades ändringar innan utgången av 2014 senaste beskeden är nu våren 2015. • Arbetet pågår i CASG Nano (Reach Competent Authorities subgroup on Nanomaterials ) Åtgärder för ökad transparens på marknaden • Kommissionen arbetar med en konsekvensutredning om åtgärder för ökad transparens på marknaden bl.a. ett EU-register för nanomaterial • Ett offentlig samråd har varit en del av arbete • Översynen ska vara klar senast i december 2014 men kommer sannolikt att försenas till våren 2015. • Översynen är uppdelad i en vetenskaplig del och en policy del. Frågor? • Konsekvensutredningen kommer att färdigställas under 2015 varpå kommissionen kan välja att föreslå åtgärder Snabb regelrepetition • Förordning (EG) nr 1223/2009 om Kosmetiska Produkter Nanomaterial i kosmetiska produkter – vad har hänt sedan de nya reglerna? Tomas Byström Enheten för Kosmetiska Produkter Läkemedelsverket • Egen definition ‘nanomaterial: ett olösligt eller biopersistent material som är avsiktligt tillverkat, med en eller fler yttre dimensioner, eller en inre struktur, med ett spann på mellan 1 och 100 nm • Arbetsgrupp har diskuterat justering av definitionen – Ingen ändring aktuell – Avvaktar hur definitionen i livsmedelsreglerna fungerar Snabb regelrepetition Vad har hänt? • Varje användning av nanomaterial måste anmälas till EU-kommissionen 6 månader före produkter släpps ut på marknaden • EU-kommissionen avgör från fall till fall om användningen behöver granskas av en vetenskaplig kommitté • 25000 produkter anmälda i hela EU – Spritt över så gott som alla kategorier – 7300 solskyddsprodukter – 7000 sminkprodukter (Carbon Black/TiO2) – 2700 ansiktsprodukter (troligen stor del dagkräm med SPF) • 150 produkter anmälda med hemvist i Sverige – 60 solskyddsprodukter – 80 sminkprodukter • Dålig kunskap hos en del företag som anmäler produkter (t ex har vatten och etanol anmälts som nanomaterial) – dock inte noterat i Sverige – – – Förhandsgranskade och tillåtna nanomaterial (UV-filter, Färgämnen, Konserveringsmedel) Granskning av produktspecifik användning (information om nanomaterialets egenskaper ska ingå i anmälan) Vägledningsdokument om säkerhetsbedömning av nanomaterial • • Safety assessment of nanomaterials in Cosmetic Products http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_s_005.pdf Relevance, Adequacy and Quality of Data in Safety Dossiers on Nanomaterials http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_142.pdf • Innehåll av nanomaterial måste framgå av innehållsförteckningen på förpackningen • EU-kommisionen ska publicera en katalog över de nanomaterial som används i kosmetiska produkter – Exempel: Titanium Dioxide (nano) • Ett ämne (UV-filter) godkänt som nanomaterial – flera släpar Utmaningar för regelutveckling Vilka nanomaterial har utvärderats • Arbetet med säkerhetsvärderingar ligger aningen sent • Ett nanomaterial tillåtet – Tris-biphenyl triazine (UV-filter) • Nanomaterial som har utvärderats av vetenskapliga kommittén, regeländring om tillåtande kvarstår – Titanium Dioxide (UV-filter) – Zinc Oxide (UV-filter) – Carbon black (CI 77266, Färgämne) – Methylene Bis-Benzotriazolyl Tetramethylbutylphenol (UV filter) – utvärdering av kompletterande data kvarstår • Pågående utvärdering – Silica med derivat • Annan utvärdering – Säkerheten hos sprayprodukter (när finns inhalationsrisk?) • Data saknas vilket gör att värderingarna inte kan fullföljas • Oklara definitioner som berör restriktioner i användning av nanomaterial (t ex sprayprodukter och inhalationsrisk) • Trög process för regeländringar som resultat av ovanstående Kommande händelser • Katalogen över nanomaterial är på översättning för snar publicering • Fullfölja regeluppdateringarna rörande förhandsgranskade och tillåtna nanomaterial • EU-kommissionen har uppmanat medlemsstaterna att utöva tillsyn för att säkerställa att företagen gör rätt – Detta med anledning av de många tokiga anmälningarna Definition av Nanomaterial i livsmedel • Förordning (EU) nr 1169/2011 om tillhandahållande av livsmedelsinformation till konsumenterna • Definition konstruerat nanomaterial: avsiktligt tillverkat material som har en eller fler dimensioner i storleksordningen 100 nm eller mindre eller som består av åtskilda funktionella delar, antingen i sitt inre eller på ytan, varav många har en eller flera dimensioner i storleksordningen 100 nm eller mindre, inbegripet strukturer, agglomerat eller aggregat, som kan vara i en storleksordning över 100 nm men behåller egenskaper som är utmärkande för nanonivån. Egenskaper som är utmärkande för nanonivå inbegriper i) de egenskaper som avser de stora särskilda ytorna hos materialet i fråga, och/eller ii) särskilda fysisk-kemiska egenskaper som skiljer sig från egenskaperna hos samma materials icke-nanoform. Tack för att ni lyssnade! 2015‐03‐26 Overview Danish initiatives on nanomaterials • Research initiatives, consumer concern and general collaboration • Action plans for chemicals • “Better control of nanomaterials” • Overview of initiatives • The nano product register • Future Flemming Ingerslev, Section of Chemicals The Danish Environmental Protection Agency The Danish Environmental Protection Agency PAGE 2 Danish Action Plans for chemicals DK outside DK-EPA (in total around 2 mio DKK for nano) • Research • 2010-2013: • Environmental Chemistry, DTU and Aarhus University • Overview of important nanomaterials • National Research Center for the Working Environment (Danish Nanosafety Center) • Proposal for REACH-annexes (IR-nano!) • University of Copenhagen and others • 2014-16: • Industry • Specific products • Consumers • International work • Politicians • Danish EPA network group for nanomaterials! The Danish Environmental Protection Agency PAGE 3 The Danish Environmental Protection Agency PAGE 4 Projects on NMs under the DK nano-initiative Better control of nanomaterials NP - register Use/occurrence of NM • New government i Denmark 3. October 2011 with a green Government Programme • National Budget Agreement 2012 on “Better Control of Nanomaterials and their Safety” (~ 3.2 mio. € 2012-2015, ) Assessment of specific products • Subproject 1: Knowledge building with focus on exposure pathways and implications for consumers and the environment with regard to the use of nanomaterials (approx. 3/4 of budget) 1. NM’s in food, food contact materials, cosmetics, pesticides 2. NM’s in pigment 3. NM’s in waste 1. Products with photocatalytic titanium dioxide 2. Aerosol products with nanomaterials 3. Textiles with nanosilver 1. Oral and dermal uptake Processes and fate of NM • Subproject 2: Development of a nano product register in cooperation with other countries (approx. 1/4 of budget) 2. Fate processes in the enviroment 3. Human exposure 4. OECD test methods Effects of NM The Danish Environmental Protection Agency Supplementary surveys Potential Environmental and health risks due to nanomaterials in DK 1. Ecotoxicology 2. Toxicology PAGE 5 1 2015‐03‐26 Projects on NMs under the DK nano-initiative NP - register Use/occurrence of NM Assessment of specific products Supplementary surveys 1. NM’s in food, food contact materials, cosmetics, pesticides 2. NM’s in pigment 3. NM’s in waste 1. Products with photocatalytic titanium dioxide 2. Aerosol products with nanomaterials 3. Textiles with nanosilver 1. Oral and dermal uptake Processes and fate of NM 2. Fate processes in the enviroment 3. Human exposure 4. OECD test methods Effects of NM The Danish Environmental Protection Agency Potential Environmental and health risks due to nanomaterials in DK 1. Ecotoxicology 2. Toxicology PAGE 7 Projects on NMs under the DK nano-initiative NP - register Use/occurrence of NM Assessment of specific products Supplementary surveys 1. NM’s in food, food contact materials, cosmetics, pesticides 2. NM’s in pigment 3. NM’s in waste 1. Products with photocatalytic titanium dioxide 2. Aerosol products with nanomaterials 3. Textiles with nanosilver 1. Oral and dermal uptake Processes and fate of NM 2. Fate processes in the enviroment 3. Human exposure 4. OECD test methods Effects of NM Potential Environmental and health risks due to nanomaterials in DK 1. Ecotoxicology 2. Toxicology Projects on NMs under the DK nano-initiative NP - register Use/occurrence of NM Assessment of specific products Supplementary surveys 1. NM’s in food, food contact materials, cosmetics, pesticides 2. NM’s in pigment 3. NM’s in waste 1. Products with photocatalytic titanium dioxide 2. Aerosol products with nanomaterials 3. Textiles with nanosilver 1. Oral and dermal uptake Processes and fate of NM 2. Fate processes in the enviroment 3. Human exposure 4. OECD test methods Effects of NM Potential Environmental and health risks due to nanomaterials in DK 1. Ecotoxicology 2. Toxicology 2 2015‐03‐26 The Ministerial Order no. 644 of 13/06/2014 / Bekendtgørelse nr. 644 of 13/06/2014 Nano Product Register Objective: • To provide an overview of the nanoproducts that are on the Danish market, the extent of use and the purposes they are used for. • To provide information to sub-project 1 (knowledge building). • To inspire to an EU-solution for registration of nano products The Danish Environmental Protection Agency PAGE 13 The Danish Environmental Protection Agency Purpose and scope of the nanoproduct register PAGE 14 § 3. Excemptions § 1. The purpose of this Order is to establish a register of mixtures and articles that contain nanomaterials (nano products) and which are intended for sale to the general public, as well as require producers and importers of these mixtures and articles to report to the nano product register information on said mixtures and articles and the nano materials they contain. § 2. The reporting requirement to the nano product register includes mixtures and articles that are intended for sale to the general public and which contain nanomaterials, where the nanomaterial itself is released under normal or reasonably foreseeable use of the mixture or article or where the nanomaterial itself is not released but substances in soluble form that are classified as CMRs or environmentally dangerous substances are released from the nanomaterial; except as provided for in § 3. 1. Foodstuffs and food contact materials. 8. Nanomaterials listed Annex IV or V of REACH (Natural substances). 2. Feed. 9. Not intentionally produced at the nanoscale. 3. Medicinal products. 10. Nanomaterial is part of a fixed matrix 4. Medical devices. 11. Articles or their labels on which the nanomaterial is used directly as ink, in newspapers etc. 5. Cosmetic products. 6. Pesticides. 7. Waste. 12. Textiles with nanomaterial used as ink or for dyeing. 13. Paint, wood preservative, glue and filler that contains nanopigment added solely for colouring the mixture. 14. Articles of rubber, or rubber parts of articles, that contain the nanomaterials carbon black or silicon dioxide The Danish Environmental Protection Agency PAGE 15 • Registration is mandatory - not all information Voluntary Information on company: ID#, adress, contakt person etc. REACH: Use descriptor categories (PC, PROC. ERC, AC) Productinformation: name, amount, use, professional use (Y/N) Content of nanomaterial: in product or mixture (gram or %) PAGE 16 Important features/characteristics Product information Mandatory The Danish Environmental Protection Agency • Registrants are those introducing the nanoproduct to the Danish marked (i.e. no intention of traceability) • Registration is not triggered by hazards or risk of nanomaterials • Re-use of information from the Danish product register • Data only available for authorities and registrant (own data) Information on the nanomaterial: Fhysical information on Name, REACH-registration, occurrence nanomaterial: particle size, number in product size distribution, aggregation, agglomeratino, form, specific surface Chemical information: IUPAC, CAS area, crystalline state, surface no., EU-number, formula chemistry, surface charge The Danish Environmental Protection Agency PAGE 17 The Danish Environmental Protection Agency PAGE 18 3 2015‐03‐26 Guidance and help for registrants Ideas for future collaboration • Guidance in Danish and English Danish EPA network group for nanomaterials • Should I register my product (nano or not?) OECD test methods • 18 illustrative examples of products Shared knowledge (reports, advisory groups) • How to use IT-system? • Example of letter to supplier • List of common nanomaterials • List of product-groups that may be subject to registration Research projects EU-work (IR-nano) • FAQ on www • Help-desk The Danish Environmental Protection Agency PAGE 19 The Danish Environmental Protection Agency PAGE 20 4 NANoREG ‐ A common European approach to the  regulatory testing of nanomaterials EU‐projekt NANoREG och nano‐cellulosa  Vad och varför? Vetenskapliga svar för  administrativa frågor Snabbare och bättre Tillförlitligt omgivning  för industrin och  myndigheterna 27.11.2014 | Kemi myndighetsmöte, Jukka Ahtiainen  Allt med samma takt med  innovationer och inte att  förhindra dom 27.11.2014 | Kemi myndighetsmöte, Jukka Ahtiainen  NANoREG project‐ facts and figures: A common European approach to the regulatory testing of nanomaterials NANoREG ‐ målsättning The NANoREG project is funded by the EU Framework 7  Programme with € 10.000.000, total budget € 50.000.000 The aims of this project are: (I) to provide tools for risk assessment and decision making instruments; The project started on March 1st, 2013 and runs until August  31st, 2016 (42 months) (II) to develop, for the long term, new testing strategies adapted to innovation  requirements; (III) to establish a close collaboration among authorities and industry to come to  61 partners from 15 countries (Austria, Belgium, Denmark,  Finland, France, Germany, Ireland, Italy, the Netherlands,  Norway, Portugal, Spain, Sweden, Switzerland, United Kingdom) efficient Risk Management approach and to bring in ”safe by design” in the  application development phase. verktyg Coordination:Ministry of Infrastructure and the Environment,  The Netherlands, Tom van Teunenbroek (coordinator) strategi tillsammans med industrin ”safe by design” – ”value chains”‐ tänkandet inbildat 27.11.2014 | Kemi myndighetsmöte, Jukka Ahtiainen  3 NANoREG‐ Work package list‐ vad det innehåller Work package No Work package title Type of  activity Lead  partici pant No Lead  participant  short name Person‐ months Start month End month RTD 2 JRC 174,6 1 42 WP1 Scientific answers to  regulatory issues WP2 Synthesis, supplying  and characterization RTD 4 NRCWE 621,20 1 42 WP3 Exposure through life  cycle analysis RTD 7 CEREGE 535,90 1 42 WP4 Biokinetics and toxicity  testing in vivo RTD 3 BAuA 680,90 1 42 WP5 Advancement of  Regulatory Risk  Assessment and Testing RTD 12 NIA 1231,60 1 42 RTD 5 RIVM 124 1 42 OTH 10 TEMAS 170 1 42 MGT 1 Min I&M 30 1 42 WP6 WP7 WP8 Keeping pace with  innovation Interaction,  Dissemination and  Exploitation Project Management total 27.11.2014 | Kemi myndighetsmöte, Jukka Ahtiainen  3568,80 Nanocellulosa och REACH  Bleached pulp cellulose (CAS‐nro:65996‐61‐4):         Exempted from REACH registration according to REACH Annex IV If grinded mechanically to NFC (without chemical modifications),  should probably (?) stay exempted. The rationale should be given by  the manufacturer. If chemically modified e.g. with covalent bounds, would be considered as a new substance,  and this would lead to obligation to register NFC nanocellulose is nanomaterial by definition Om så här nanocellulosa behövs inte registreras Men om den formuleras med kemikaliska metoden? Och vad ska man då registreras när det är en polymer? Inget nytta att registrera monomer 27.11.2014 | Kemi myndighetsmöte, Jukka Ahtiainen  NANoREG och nanocellulosa (Nano Fibril Cellulose)  Finska koordinering på Säkerhets‐ och kemikalieverket (Tukes)  Samarbetet med industrin, forskning och myndigheten  UPM Corporation och Stora Enso (pengar finns här)  Toksikologiska (andningsorgan) studier på Arbetshälsoinstitutet i Helsingfors  Målet: “… to assess the in vivo and in vitro genotoxic and immunotoxic effects of nanofibrillar cellulose (NFC)” 27.11.2014 | Kemi myndighetsmöte, Jukka Ahtiainen  Tack! Box 2, 172 13 Sundbyberg 08-519 41 100 Besöks- och leveransadress Esplanaden 3A, Sundbyberg [email protected] www.kemikalieinspektionen.se