Project information European Research on Environment and Health Funded by the Sixth Framework Programme Snapshots of final results KI-NA-25-049-EN-C Sixty-six multidisciplinary pan-European research projects dealing with environment and health issues were funded by the European Commission’s Research Directorate- General (now called DG Research and Innovation) in the Sixth Framework Programme of Research (20022006). The main results are presented in this catalogue. All of these projects have now ended and have produced a wealth of new and interesting results that have improved the science base and that have the potential to support various EU policies. The projects presented addressed a multitude of issues ranging from health impacts of climate change to improved integrated environment and health risk assessment methodologies. This overview should be useful to many stakeholders policy makers at national, EU and global level. European Research on Environment and Health Funded by the Sixth Framework Programme Research and Innovation EuropeanResearchOnEnvironment&HealthFundedByFP6 COVER PgsLim 06 indd 1-3 KINA25049ENC_001.pdf 1 1/06/12 11:58 25/07/12 10:50 How to obtain EU publications Free publications: a SF>#2 LLHPELMEQQM?LLHPELMBROLM>BR a >QQEB#ROLMB>K2KFLK|POBMOBPBKQ>QFLKPLOABIBD>QFLKP6LR@>KL?Q>FKQEBFO@LKQ>@QABQ>FIPLKQEB 'KQBOKBQEQQMB@BROLM>BRLO?VPBKAFKD>C>UQL Priced publications: a SF>#2 LLHPELMEQQM?LLHPELMBROLM>BR a SF>LKBLCQEBP>IBP>DBKQPLCQEBÅR?IF@>QFLKP-ȵ@BLCQEB#ROLMB>K2KFLK EQQMMR?IF@>QFLKPBROLM>BRLQEBOP>DBKQPFKABU<BKEQJ EUROPEAN COMMISSION Directorate-General for Research and Innovation Directorate I – Environment Unit I.4 – Climate Change and Natural Hazards E-mail: [email protected] Contact: Tuomo Karjalainen European Commission B-1049 Brussels E-mail: [email protected] [email protected] EuropeanResearchOnEnvironment&HealthFundedByFP6 COVER PgsLim 06 indd 4-6 KINA25049ENC_001.pdf 2 1/06/12 11:58 25/07/12 10:50 EUROPEAN COMMISSION European Research on Environment and Health Funded by the Sixth Framework Programme 2012 Directorate-General for Research and Innovation EUR 25049 EN ! 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( #.$ 1SJOUFEJO#FMHJVN TABLEOFCONTENTS -3- 4 TableofContents EUfundingofresearchonenvironmentandhealthinFP5andFP7 EUfundingofresearchonenvironmentandhealthinFP6 Environmentandhealthissuesaddressedbytheprojectsfunded Projectdata ChapterI:Projectsfocusedoncoordination,harmonisation,networking,policysupport EMFNET:Effectsoftheexposuretoelectromagneticfields:fromsciencetopublichealthand saferworkplace ENVIE:Coordinationactiononindoorairqualityandhealtheffects EPIBATHE:Assessmentofhumanhealtheffectscausedbybathingwaters ESBIO:DevelopmentofacoherentapproachtohumanbiomonitoringinEurope HENVINET:Healthandenvironmentnetwork PHOEBE:Harmonisingpopulationbasedbiobanksandcohortstudiestostrengthenthefoundationof Europeanbiomedicalscienceinthepostgenomeera PRONET:Pollutionreductionoptionsnetwork VIROBATHE:MethodsforthedetectionofadenovirusesandnorovirusesinEuropeanbathingwaters withreferencetotherevisionoftheBathingWaterDirective76/160/EEC ChapterII:Projectsfocusedontheeffectsofexposuretoenvironmentalstressorsandunderlying mechanisms ATHON:AssessingthetoxicityandhazardofnondioxinlikePCBspresentinfood CASCADE:Chemicalsascontaminantsinthefoodchain:aNoEforresearch,riskassessmentand Education DEVNERTOX:Toxicthreatstothedevelopingnervoussystem:invivoandinvitrostudiesonthe effectsofmixtureofneurotoxicsubstancespotentiallycontaminatingfood DIEPHY:DietaryexposurestopolycyclicaromatichydrocarbonsandDNAdamage ECNIS:Environmentalcancerrisk,nutritionandindividualsusceptibility EUROPREVALL:Theprevalence,costandbasisoffoodallergyacrossEurope FOOD&FECUNDITY:Pharmaceuticalproductsashighriskeffectors FURANRA:Roleofgeneticandnongeneticmechanismsinfuranrisk GABRIEL:Amultidisciplinarystudytoidentifythegeneticandenvironmentalcausesofasthmainthe EuropeanCommunity GA2LEN:GlobalallergyandasthmaEuropeannetwork MONIQA:Towardstheharmonisationofanalyticalmethodsformonitoringqualityandsafetyinthe foodchain NEWGENERIS:Newbornsandgenotoxicexposurerisks:Developmentandapplicationofbiomarkersof dietaryexposuretogenotoxicandimmunotoxicchemicalsandofbiomarkersofearlyeffects, usingmotherchildbirthcohortsandbiobanks PHIME:Publichealthimpactoflongterm,lowlevelmixedelementexposureinsusceptible populationstrata PIONEER:Pubertyonset–influenceofnutritional,environmentalandendogenousregulators 5 9 15 33 65 67 69 73 75 77 81 85 87 91 95 97 99 103 105 109 113 117 121 125 129 133 137 141 145 TableofContents ChapterIII:Projectsfocusedonthedevelopmentofmethodsandtoolsforenvironmentandhealth riskandimpactassessment BENERIS:Benefitriskassessmentforfood:aniterativevalueofinformationapproach DROPS:Developmentofmacroandsectoraleconomicmodelsaimingtoevaluatetheroleof publichealthexternalitiesonsociety ENVIRISK:Assessingtherisksofenvironmentalstressors:contributiontothedevelopmentof integratingmethodology ESPREME:IntegratedassessmentofheavymetalreleasesinEurope 2FUN:Fullchainanduncertaintyapproachesforassessinghealthrisksinfutureenvironmental scenarios HEIMTSA:Healthandenvironmentintegratedmethodologyandtoolboxforscenarioassessment INTARESE:IntegratedassessmentofhealthrisksfromenvironmentalstressorsinEurope METHODEX:Methodsanddataonenvironmentalandhealthexternalities:harmonising andsharingofoperationalestimates NOMIRACLE:NovelmethodsforintegratedriskassessmentofcumulativestressorsinEurope QALIBRA:Qualityoflife–integratedbenefitandriskanalysiswebbasedtoolforassessingfood safetyandhealthbenefits SAFEFOODS:Promotingfoodsafetythroughanewintegratedriskanalysisapproachforfoods VERHICHILDREN:Valuationofenvironmentrelatedhealthimpactsforchildren ChapterIV:Projectsfocusedonthedevelopmentofinvitrotoxicitytestingstrategies ACUTETOX:Optimizationandprevalidationofaninvitroteststrategyforpredictinghumanacute toxicity CAESAR:Computerassistedevaluationofindustrialchemicalsubstancesaccordingtoregulations CARCINOGENOMICS:Developmentofahighthroughputgenomicsbasedtestforassessinggenotoxic andcarcinogenicpropertiesofchemicalcompoundsinvitro EXERA:Developmentof3Dinvitromodelsofestrogenreportermousetissuesforthepharmaco toxicologicalanalysisofnuclearreceptorsinteractingcompounds(NRICs) OSIRIS:Optimizedstrategiesforriskassessmentofindustrialchemicalsthroughintegration ofnontestandtestinformation PREDICTOMICS:Shortterminvitroassaysforlongtermtoxicity REPROTECT:Developmentofanovelapproachinhazardandriskassessmentorreproductive toxicitybyacombinationandapplicationofinvitro,tissueandsensortechnologies SENSITIV:Noveltestingstrategiesforinvitroassessmentofallergens ChapterV:Projectsfocusedonemergingrisks CELLNANOTOX:Cellularinteractionandtoxicologywithengineerednanoparticles CIRCE:Climatechangeandimpactresearch:theMediterraneanenvironment DIPNA:Developmentofanintegratedplatformfornanoparticleanalysistoverifytheirpossible toxicityandtheecotoxicity EDEN:EmergingdiseasesinachangingEuropeanenvironment ENSEMBLES:ENSEMBLEbasedpredictionsofclimatechangesandtheirimpacts HEALTHYWATER:Assessmentofhumanhealthimpactsfromemergingmicrobialpathogensin drinkingwaterbymolecularandepidemiologicalstudies HIWATE:Healthimpactsoflongtermexposuretodisinfectionbyproductsindrinkingwater 6 147 149 151 155 157 159 136 167 171 173 177 181 185 187 189 193 195 199 203 207 209 213 217 219 223 227 229 233 237 241 TableofContents IMPART:Improvingtheunderstandingoftheimpactofnanoparticlesonhumanhealthandthe environment MICRODIS:Healthandsocioeconomicimpactsofextremeevents NANOINTERACT:Developmentofaplatformandtoolkitforunderstandinginteractions betweennanoparticlesandthelivingworld NANOSAFE2:Safeproductionanduseofnanomaterials NANOSH:Inflammatoryandgenotoxiceffectsofengineerednanomaterials NORMAN:Networkofreferencelaboratoriesandrelatedorganisationsformonitoringofemerging environmentalpollutants PARTICLE_RISK:Riskassessmentforparticleexposure POLYSOA:Polymersinsecondaryorganicaerosols ChapterVI:Otherprojectsofinterest 1 AnnexAParticipatingcountriesandinstitutesinFP6fundedenvironmentandhealthprojects AnnexBVariousissuesaddressedbyFP6projects AnnexCEnvironmentalfactors(stressors)addressedbyFP6projects AnnexDHealthendpointsaddressedbyFP6projects 1 COSTactions,projectswithminorrelevancetohumanhealth,specificsupportactionsnot carryingoutresearch 7 245 249 253 257 261 265 269 271 273 277 311 331 337 8 EUFundingofResearchonEnvironmentandHealthinFP5andFP7 EUFUNDINGOFRESEARCH ONENVIRONMENTAND HEALTHINFP5ANDFP7 9 10 EUFundingofResearchonEnvironmentandHealthinFP5 EnvironmentandhealthresearchfundedbytheFifthFramework Programme(FP5–19982002) FP5wasthefirstEUresearchframeworkprogramme in which a dedicated environment and health research activity emerged. Environment and health researchwasmainlyfundedbytheQualityofLifeand ManagementofLivingResourcesthemeofFP5,which had a key action entitled 'Environment and Health'. Withabudgetof€160millionovertheperiod1998– 2002, this key action initiated more than 90 trans nationalresearchprojects,theresultsfromwhichare 2 available . The last projects ended in 2008, although some additional results became available later. Projects pertaining to ecotoxicological aspects were also funded by two key actions within the Energy, Environment and Sustainable Development programme. SelectedresultsfromFP5projects: 9 Theadverserespiratoryhealtheffectsoffineparticles,nitrogenoxidesandin particular smoking were widely demonstrated. The use of biomarkers to give earlyindicationofeitherpotentialtodevelopdiseaseorevidenceofexposure showed the utility of this emerging science for a variety of environmental stressors. These results have effectively fed into the EU policy process on air pollution; 9 Endocrinerelated reproductive effects were widely studied showing correlationsbetweenexposuretoarangeofchemicalsandadverseeffectsina variety of animal models ranging from invertebrates to various mammals. Humanstudiesshowed,amongothers,thatreproductivehealthisdeteriorating inseveralregionsinEuropeasevidencedbydecliningspermcountsandother parameters, but causes behind this change remain unclear. In addition, developmental and/or neurobehavioural effects of some chemicals were observedinanimalsaswellasinexposedhumanpopulations; 2 http://ec.europa.eu/research/environment/pdf/env_health_projects/env_health_brochure.pdf; http://ec.europa.eu/research/environment/themes/projects_en.htm#2 11 EUFundingofResearchonEnvironmentandHealthinFP5 9 9 Fears about the adverse health effect of mobile phone use and other electromagnetic sources were not supported by research findings, although it canbeconcludedthatmoreresearchisneededtodrawcausalconclusions; Clear evidence of links between transport noise, classroom performance and health indicators were made. Noise can have adverse effects on the cardiovascularsystem. 12 EUFundingofResearchonEnvironmentandHealthinFP7 EnvironmentandhealthresearchfundedbytheSeventh FrameworkProgramme(FP7–20062013) Running from 2007 to 2013, FP7 has a budget of 53.2 billion euros over its seven year lifespan, the largest funding allocation yet for the EU research framework programmes. It is designed to build on the achievements of its predecessors towards the creation of the European Research Area and carry it further towards the development of the knowledgeeconomyandsocietyinEurope.Since 2010, renewed emphasis has been put on innovation aspects of the programme to promote growth and jobs, also in anticipation of the next framework programme, Horizon 2020 theFrameworkProgrammeforResearchandInnovation. The research activities funded by the FP are mainly managed by two Directorates 3 General (DGs) in the European Commission: DG Research and Innovation and DG 4 InformationSocietyandMedia .SomeactivitiesarealsofundedbyotherDGssuch 5 asDGEnterpriseandIndustryandDGMOVE . th More information on the 7 Framework can be found on the CORDIS website 6 dedicatedtoEuropeanresearch .Asynopsisandanalysisof the projects in the environment and health area from the 7 firstfivecallsforproposalshasbeenpublished .Themain funding for research has come from the specific 'Environment and Health' subactivity, embedded in the Environment(includingClimateChange)theme. 3 http://ec.europa.eu/research http://ec.europa.eu/dgs/information_society/index_en.htm 5 http://ec.europa.eu/enterprise/index_en.htm 6 http://cordis.europa.eu/fp7/home_en.html 7 http://ec.europa.eu/research/environment/pdf/fp7_catalogue_eh.pdf; http://ec.europa.eu/research/environment/pdf/fp7_catalogue_eh_projects_september_2011.pdf 4 13 14 EUFundingofResearchonEnvironmentandHealthinFP6 EUFUNDINGOFRESEARCH ONENVIRONMENTAND HEALTHINFP6 15 16 EUFundingofResearchonEnvironmentandHealthinFP6 Introduction This catalogue describes and analyses in some detail 66 projects selected from the four calls for proposals launched by the European Commission in FP6 (specific supportactions,whicharenotresearchprojects,arenotincluded;theyarelistedat theendofthischapter).Itshouldbenotedthatprojectswhichhaveonlyaminoror indirect health and/or environmental component have been included (e.g., 8 9 10 ENSEMBLES ,CIRCE ,SAFEFOODS )forthesakeofcompletenessandrelevanceto environmentandhealthrelevantpolicies. The 66 projects represent 612 participating institutions from 58 countries from all overtheworldandhavereceivedatotalEUcontribution€316M(€79Mperannum) or€283M(€71Mperannum)ifthethreeprojectsmentionedaboveareomitted. Thesespendinglevelsrepresentasubstantialincreaseascomparedtothespending in FP5, where approximately €40M per annum were allocated to environment and healthresearch. In addition to more traditional smalltomedium scale specific targeted research projects (STREPs) and coordination actions (CAs), FP6 saw the introduction of two new funding instruments, namely integrated projects (IPs) and networks of 11 excellence(NoEs) . x Theintegratedprojectwasaninstrumenttosupportobjectivedrivenresearch, where the primary deliverable was new knowledge. The projects were quite large(thelargestprojectinthiscataloguehas69participatinginstitutions)with asubstantialbudgetandlongduration(usuallyfiveorsixyears); x Networks of excellence were designed to strengthen scientific and technological excellence on a particular research topic by integrating at Europeanlevelthecriticalmassofresourcesandexpertiseneededtoprovide European leadership and to be a world force in that topic. This expertise was networkedaroundajointprogrammeofactivitiesaimedprincipallyatcreating aprogressiveanddurableintegrationoftheresearchcapacitiesofthenetwork partnerswhile,ofcourse,atthesametimeadvancingknowledgeonthetopic. OnlyfourNoEswerefundedintheenvironmentandhealthareainFP6,allby ThematicPriority5(FoodQualityandSafety).Theyhadupto34participating institutionsandhadasimilardurationtothatofIPs. 8 ENSEMBLESEnsemblebasedpredictionsofclimatechangesandtheirimpacts www.ensembleseu.org 9 CIRCEClimatechangeandimpactresearch:theMediterraneanenvironment www.circeproject.eu 10 SAFEFOODSPromotingfoodsafetythroughanewintegratedriskanalysisapproachforfoods www.safefoods.wur.nl 11 http://cordis.europa.eu/fp6/instruments.htm 17 EUFundingofResearchonEnvironmentandHealthinFP6 One of the main drivers for environment and health research during the course of FP6hasbeentheEuropeanEnvironmentandHealth StrategyandtheassociatedActionPlan,adoptedin 12 2004 , the first phase of which cam to an end in 2010. This initiative aimed to improve our understanding of the links between environmental factorsandhealthandwaspartiallyinspiredbythe needtolinkpolicywithresearchresults.TheActionPlanhasservedasacatalystto increaseresearchspendingattheEUlevel,i.e.,FP6.FouroftheactionsintheAction Planwererelatedtoresearch. Theavailabilityofextraresourcesandpolicysupporthasallowedtheconcentration andrefocusingofeffortstobuildupaEuropeanResearchAreainspecificfieldsof environmental health science. The research/policy interface was enhanced by the introductionintheFP6ofaspecific'ScientificSupporttoPolicy'programme,which allowed the close exchange of ideas between research and policymakers and the discussionofpolicyoptionsandpolicyimplicationsofresearchundertaken. Astudycarriedoutbyanexternalimpactassessmentbody on the longerterm impact of European Union funding of research in the field of Environment and Health was fundedbyDGResearchandInnovationin2010.Thestudy concluded,interalia,that x There is objective evidence that projects funded by theFPshavecontributedtonumerousEUpolicies:EU researchonenvironmentandhealthhasalreadyhad importantpolicyimpact; x AnimportantlongertermimpactoftheEUfundingis that the environment and health research has created an important common European research platform with a very high degreeoflegitimacyamongtheactors.Actorsexpressedawishtoincreasethe Europeancooperationonenvironmentandhealthresearchfurtherintheyears tocome; x NationallevelstakeholdersaremoreconvincedthanEUlevelstakeholdersthat the funded research projects/activities in the area of environment and health havecomplementedand/orcontributedtonationalpolicies/actions; x Gaps remain both at research and policy levels that need to be filled in the future. Thedetailedconclusionsarepublicallyavailableinareport. 12 http://europa.eu/legislation_summaries/environment/general_provisions/l28133_en.htm 18 EUFundingofResearchonEnvironmentandHealthinFP6 Environment and health research funded by FP6 has fed and has the potential to feedintoalargenumberofpolicyinitiativessuchasTheEuropeanEnvironmentand Health Action Plan, the EU Sustainable Development Strategy, the Community Strategy for Endocrine Disrupters and the REACH regulation on chemicals. Each of theprojectsheetsincludedinthiscatalogueidentifiesthemainpoliciestowhichthe projectcouldcontributeorhascontributedalready. By the end of 2011 all except one project have ended and thus final results are available. However, it should be noted that many projects still continue publishing resultsinscientificjournals,andsomeactivitiescontinueinotherprojectsfundedby FP7. 19 20 EUFundingofResearchonEnvironmentandHealthinFP6 Researchprogrammesandtrendsoffundingenvironmentand healthresearchinFP6 Environment and health research has a very wide scope and is of multidisciplinary nature. For this reason, funding for this activity spans across several thematic programmesandDirectoratesintheEuropeanCommission'sDirectorateGeneralfor Research (currently called DG Research and Innovation). Thus, several sources of fundingoccurredusingvariousfundinginstrumentsorschemes. As seen in Fig. 1 and Table 1, the main funding area for environment and health research projects in FP6 was the 'EnvironmentalHealthRisks'areaoftheThematicPriority5(Food Quality and Safety). It funded 20 projects with a total EC contribution of around €128M. This represents 30% of all projectsand41%ofthetotalECcontributiontoenvironmentand healthresearch. The Thematic priority 6 (Sustainable Development, Global Change and Ecosystems) and 1 (Life Sciences; Innovative Medicines Initiative, PovertyRelated Diseases, Stem Cells) funded 16 and 12 projects, respectively. This represents 24% and 18% (at EC contribution level: 28% and 21%) of all projects, respectively. The Thematic Priority 1 projects were predominated by those addressingthedevelopment ofalternativetoxicitytestingmethods,whereasPriority 6fundedprojectsweremorediverse. Unlike in the past, some funding started to emerge for nanotoxicological research from the Thematic priority 3 (Nanotechnologies and Nanoscience, KnowledgeBased Multifunctional Materials, and New Production Processes and Devises).11%oftheprojects,representing6%ofallFP6budget for environment and health projects, were funded from this ThematicPriority. FP6hadaspecificareadevotedtoscientificsupporttopolicies(oftenreferredtoas 'Priority8').Inthisareathecalltopicswereelaboratedinclose collaboration with the policy DirectoratesGeneral of the 21 EUFundingofResearchonEnvironmentandHealthinFP6 EuropeanCommission.Thenineprojectsfundedintheenvironmentandhealtharea represent 14% of all projects funded but only 4% of total funding (the projects fundedwererathersmall). Sustained–andevenincreasedfundingbyFP6toenvironmentandhealthresearch can be speculated to be attributable to several factors, including continued public concern for environment and health issues, the impetus provided by the European Environment and Health Action Plan 20042010, and support from policy DirectorateGenerals in the Commission, which recognise that to implement a numberofpoliciesattheEUlevelscientificsupportisneeded.Forthesereasonsthe three research framework programmes (FP5, FP6, FP7) have each had a dedicated environmentandhealthresearchactivityorsubactivity. 22 EUFundingofResearchonEnvironmentandHealthinFP6 Fig.1. SchematicrepresentationofEUfundingtoenvironmentandhealthrelatedresearch byvariousthematicprioritiesinFP6 140 120 100 80 No. of projects EU contribution (€M) 60 40 20 0 No. of projects EU contribution (€M) 1 3 5 6 8 12 7 20 16 9 NEST 2 65,3 19,2 127,9 89,8 12,4 1,6 1=Thematicpriority1:LifeSciences;InnovativeMedicinesInitiative,PovertyRelated Diseases,StemCells 3=Thematicpriority3:NanotechnologiesandNanosciences,KnowledgeBased MultifunctionalMaterials,andNewProductionProcessandDevises 5=Thematicpriority5:FoodqualityandSafety('Environmentalhealthrisks'sub area) 6=Thematicpriority6:SustainableDevelopment,GlobalChangeandEcosystems (Complementaryresearchsubarea) 8=ScientificSupporttoPolicy(socalled'Priority8'):Policyorientedresearchin specificactivitiescoveringwiderfieldofresearch NEST=NewandEmergingScienceandTechnologyprogramme 23 EUFundingofResearchonEnvironment andHealthinFP6 Table1. ThematicprioritiesandotherFP6programmesfromwhich environmentandhealthrelatedactivitieswerefunded Mainenvironmentandhealthissueaddressed Nbprojects EUcontri bution (€M) ThematicPriority1LifeSciences;InnovativeMedicinesInitiative,PovertyRelated Diseases,StemCells Developmentoftoxicitytestingmethods 9 Coordinationofresearchonbiobankingandcohorts 1 0.8 Environmentalcausesofallergy/asthma 1 11.3 Roleofchemicalsondevelopmentandageing Total 43.2 1 10.0 12 65.3 Thematicpriority3NanotechnologiesandNanoscience,KnowledgeBased MultifunctionalMaterials,andNewProductionProcessesandDevises Invitrotoxicityofnanoparticles 3 8.7 Coordinationofnanotoxicologyresearch 2 1.1 Invitroandinvivotoxicityofnanoparticles 1 2.4 Safetyofnanomaterials Total 1 7.0 7 19.2 ThematicPriority5Foodqualityandsafety('Environmentalhealthrisks'subarea) Food/environmentalcontaminantsforchemicalrisk assessment 9 58.2 Methodologiesandmodelsforrisk/benefitanalysisof foodcontaminants 4 14.7 Environmentalcancerrisks 2 11.4 Environmentalcausesofallergy/asthma 2 28.7 Detection/monitoringofenvironmental/food contaminants 1 12.3 Developmentoftoxicitytestingmethods 1 0.2 Waterbornemicrobialcontaminantsfor microbiologicalriskassessment 1 2.4 20 127.9 Total 24 EUFundingofResearchonEnvironmentandHealthinFP6 ThematicPriority6Sustainabledevelopment,globalchangeandecosystems (Complementaryresearchsubarea) Methodologiesandmodelsforintegratedenvironment andhealthrisk/impactassessment 5 29.9 Coordinationofresearch 3 5.5 Impactsofclimatechange 3 36.5 Methodologiesandmodelsforcost/benefitanalysisof environmentalcontaminants 3 2.9 Impactsofextremeevents 1 5.0 Developmentoftoxicitytestingmethods 1 10.0 16 89.8 Total 13 'Priority8 'Policyorientedresearchinspecificactivitiescoveringawiderfieldof research Coordinationofresearchonindoorairquality 2 1.6 Waterbornemicrobialcontaminantsfor microbiologicalriskassessment 2 4.2 Food/environmentalcontaminantsforchemicalrisk assessment 1 1.5 Coordinationofresearchonhealtheffectsofnon ionisingradiation(electromagneticfields) 1 1.5 Coordinationofresearchonbiomonitoringof environmentalcontaminants 1 1.1 Developmentoftoxicitytestingmethods 1 1.5 Valuationofenvironmentrelatedhealthimpacts 1 1.0 9 12.4 Riskassessmentofairpollution 2 1.6 Total 2 1.6 Grandtotal 66 316.2* Total NESTNewandemergingscienceandtechnologies *Thegrandtotalisapprox.€283Mifthreeprojectswithonlyaminorhealth component(ENSEMBLES,SAFEFOODSandCIRCE)areexcluded 13 Notanofficialterm,butwasfrequentlyusedforthisactivity 25 EUFundingofResearchonEnvironmentandHealthinFP6 Projecttypes Amongst the project types funded from the various Thematic Priorities, there is a clear predominance of specific targeted research projects (STREPs 39% of all projects funded; average EU contribution of €2M per project) and integrated projects(IPs;30%ofallprojectsfunded;average€10.4Mperproject).Theaverage number of participants in STREPs was 10 (smallest 4, largest 19 participating institutions),whichishigherthantheaverageinFP5.Theaveragenumber–36of participantsinIPsismuchhigher(smallest19,largest68participatinginstitutions). There are differences between the various Thematic Priorities: IPs were used as a fundinginstrumentespeciallybyThematicPriority1and6. DuetothelargenumberandtopicareasofSTREPsfunded,itisdifficulttohighlight theirachievements.NotableintegratedprojectsfundedbyFP6includethoseaiming at finding alternative methods and intelligent testing strategies for chemicals (e.g., 14 15 16 REPROTECT , ACUTETOX , OSIRIS ), promoting integrated environment and 17 18 health impact and risk assessment methodologies (INTARESE and HEIMTSA ) or exploring the risk for spreading of infectious diseases due to climate change 19 (EDEN ).Inadditiontoadvancingscientificknowledgeandproducingnewdata,IPs alsoundertookmanytraininganddisseminationactivitiesandresearcherexchanges werecommonwithinEuropeandbeyond. The introduction of networks of excellence as a funding scheme in FP6 to fight fragmentation resulted in the funding of four projects only, all in the Thematic Priority5.TheaverageEUcontributiontoaNoEwas€13Mandtheaveragenumber ofparticipatinginstitutions26(range19to34).Thesmallernumberofparticipating institutionsmayreflectthefactthattherewasarequirementfordurableintegration for this type of funding instrument; it would be easier with a smaller number of participants.Inadditiontotheirscientificaccomplishments,themajorachievement of Networks of Excellence was the numerous training activities offered both to network participants and beyond, in addition to many targeted dissemination activitiesengagingmanytypesofstakeholders. 14 REPROTECTDevelopmentofanovelapproachinhazardandriskassessmentorreproductive toxicity by a combination and application of in vitro, tissue and sensor technologies www.reprotect.eu 15 ACUTETOXOptimisationandprevalidationofaninvitroteststrategyforpredictinghuman acutetoxicitywww.acutetox.eu 16 OSIRIS Optimized strategies for risk assessment of chemicals based on intelligent testing www.osiris.ufz.de 17 INTARESE Integrated assessment of health risks from environmental stressors in Europe www.intarese.org 18 HEIMTSA Health and environment integrated methodology and toolbox for scenario assessmentwww.heimtsa.eu 19 EDENEmergingdiseasesinachangingEuropeanenvironmentwww.edenfp6project.net 27 EUFundingofResearchonEnvironmentandHealthinFP6 The four networks of excellence were projects dealing with allergy and asthma 2 20 21 (GA LEN ), environmental cancer risks (ECNIS ), endocrine disrupting chemicals 22 (CASCADE ) and harmonisation of analytical methods for monitoring quality and 23 safetyinthefoodchain(MONIQA ). x GA²LEN has achieved sustainability and is continuing as a nonprofit network, building on the foundation provided by the six years of FP6 funding. This network,GA²LENe.V.,isbasedattheCharitéHospital inBerlin. GA²LENprovidescontinuoussupporttoEU initiativesbutiscurrentlyseekingfurtherfundingnot only for the durable structure but also to allow the outputs needed to offer panEuropeansurveillanceonallergiesforEUpolicies. x The ECNIS NoE was only the first stage of the processofcreatingastronglyintegratedandviable Europeanresearchnetwork.Havingdrawntogether themostrelevantpartiestowardsthistaskandalso having identified the major gaps in available data and biomarker validation, the network deemed it as necessary to cement the integrationonamorepermanentbasis.Thisideahasbecomeamajorgoalof theECNIS2project,fundedbytheSeventhFrameworkProgrammeofResearch, with an ultimate goal of transforming network into a virtual centre, the EuropeanCentreforResearchandEducationonCancer,EnvironmentandFood (ECRECEF). x Aftersixbusyyears,CASCADENoEbecomeCASCADEACERT, a nonprofit association, which will continue to offer training, risk assessment and collaborative partnership as the leading European network within endocrine research. An international postdoctoral programme (CASCADE FELLOWS) to continue the research and researcher exchangeactivitiesofCASCADEhasbeenestablished. x Atameetingheldin2010,theMONIQA Governing Council decided that sustainability of MONIQA will be 20 GA2LENGlobalallergyandasthmaEuropeannetworkwww.ga2len.net ECNISEnvironmentalcancerrisk,nutritionandindividualsusceptibilitywww.ecnis.org 22 CASCADEChemicalsascontaminantsinthefoodchain:ANoEforresearch,riskassessment andeducationwww.cascadenet.org 23 MONIQATowardstheharmonisationofanalyticalmethodsformonitoringqualityandsafety inthefoodchainwww.moniqa.org 21 28 EUFundingofResearchonEnvironmentandHealthinFP6 implemented through a new legal entity. This new entity, referred to as MoniQA Association, was launched in 2011. It is registered as a nonprofit distributing association (Verein) established in Vienna, Austria and subject to thelawsofthatjurisdiction.TheMoniQAAssociationisaninternationalgroup of organisations dedicated to promoting safer food by, e.g., promoting harmonisationofanalyticalapproachesinfoodsafetyandqualityandproviding infrastructure for, and establishing, an international network for inter laboratoryvalidationtrialsforanalyticalmethodsandreferencematerials. Coordinationactionsaimtopromoteandsupportthenetworkingandcoordination of research and innovation activities. They can cover activities such as the organisation of conferences, performance of studies, exchanges of personnel or dissemination of good practices. Throughout the recent framework programmes a rather constant proportion of projects have been coordination actions (CA), in FP6 receiving an average EU contribution of around €1.3 M. The average number of participating institutions was 21 (range from 8 to 41). The coordination actions do notallowresearchactivitiestobefundedbutareaimedtosupportcoordinationand harmonisation of researchrelevant actions. They oftentimes identify research gaps 24 and are sometimes followed by more targeted research projects (e.g., ENVIE in 25 FP6,OFFICAIR inFP7). Three highprofile coordination actions were funded by the 'Scientific Support to 26 Policy' programme in FP6, namely EMFNET on health risks related to 27 28 electromagnetic fields, ENVIE on indoor air quality, and ESBIO on harmonising humanbiomonitoringinEurope. Inadditiontothefourprojecttypesmentionedabove,eightspecificsupportactions were funded in FP6. This funding instrument is used for activities such as organisationofconferences,operationalsupportanddissemination.Theseprojects arelistedinChapterVI. 24 ENVIE Coordination action on indoor air quality and health effects www.envie iaq.eu/home.html 25 OFFICAIROnthereductionofhealtheffectsfromcombinedexposuretoindoorairpollutants inmodernofficeswww.officairproject.eu 26 EMFNETEffectsoftheexposuretoelectromagneticfields:fromsciencetopublichealthand saferworkplacehttp://web.jrc.ec.europa.eu/emfnet 27 ENVIECoordinationactiononindoorairqualityandhealtheffectswww.envie iaq.eu/home.html 28 ESBIO–DevelopmentofacoherentapproachtohumanbiomonitoringinEuropewww.eu humanbiomonitoring.org/sub/esbio.htm 29 EUFundingofResearchonEnvironmentandHealthinFP6 CountriesandinstitutesparticipatinginFP6fundedenvironment andhealthrelatedresearchprojects All but one (Malta) EU member states were representedintheprojectsfundedbyFP6.Asseen in Fig. 2 and Annex A, Great Britain, Germany and Italy participated in over 40 projects, Belgium, Finland,France,theNetherlands,SpainandSweden in over 30 projects, and the Czech Republic, Denmark, Greece, and Poland in over 20 projects. Germany and Great Britain had the greatest numberofparticipatinginstitutionsaswell(over80each),followedbyItaly,France, Spain,theNetherlands,SwedenandPoland. FromotherEuropeancountriesthelargestparticipationwasthatofSwitzerland(23 institutionsin21projects),followedbyNorway(30institutionsin21projects). FromoutsideEurope,participantsincluded: 9Africancountries; 5countriesfromtheAmericas; 9 Asian countries, with Israel having a significant participation with 11 participatinginstitutionsin7projects; AustraliaandNewZealand. As regards the participation of international organisations, the United Nations was representedbyfourinstitutions,includingtheWorldHealthOrganization.TheJoint ResearchCentreparticipatedin20projects.Theother19internationalparticipants included associations funded by industry, and patient and other nongovernmental organisations. Table 2 gives an overview of the most active participating institutes in FP6 environmentandhealthrelatedresearchprojects. 31 EUFundingofResearchonEnvironmentandHealthinFP6 Fig.2. ParticipatingcountriesandinstitutesinFP6environmentandhealthrelatedprojects 100 90 80 70 60 No. of projects 50 No. of institutes 40 30 20 10 0 AT BE BU CY CZ DK EE FI FR DE EL HU IE IT LV LT LU NL PL No. of projects 17 31 7 2 22 24 4 33 35 49 20 14 12 45 3 6 2 38 27 9 4 8 8 32 34 51 No. of institutes 17 17 5 1 13 19 3 18 65 88 16 14 14 72 3 5 2 31 21 PT RO 8 8 SK 6 SI 6 ES 54 SE 24 UK 82 Table2. ThemostactiveinstitutionsparticipatinginFP6projects Nb Institute 20 JointResearchCentre(JRC),Ispra(IT) 14 KarolinskaInstitute,Stockholm/Huddinge(SE) 13 NationalInstituteforPublicHealthandtheEnvironment(RIVM),Bilthoven(NL) 11 ImperialCollegeofScience,TechnologyAndMedicine,London(UK) 10 UtrechtUniversity(NL) 9 NationalInstituteforHealthandWelfare(THL),Helsinki/Kuopio(FI);FlemishInstitutefor TechnologicalResearch(VITO),Mol(BE);InstituteofAppliedScientificResearch(TNO), variouslocations(NL);NationalHealthInstitute(ISS),Rome(IT);NationalInstituteof HealthandMedicalResearch(INSERM),variouslocations(FR);NoferInstituteof OccupationalMedicine,ód(PL) 8 CharlesUniversity,Prague(CZ);VUUniversity,Amsterdam(NL) 7 CatholicUniversityofLouvain,Brussels/LouvainlaNeuve(BE);NorwegianInstitutefor AirResearch(NILU),Kjeller(NO);StockholmUniversity,SE;TechnicalUniversityof Denmark,KongensLyngby(DK); 6 AarhusUniversity,Aarhus/Roskilde(DK);FraunhoferInstitute,variouslocations(DE); FreeUniversityofBrussels(BE);HelmholtzResearchCentreforEnvironmentalHealth, Munich(DE);InstituteofPharmacologicalResearchMarioNegri,Milan(IT);Maastricht University(NL);MaxPlanckInstitute,variouslocations(DE);UniversityofEastAnglia, Norwich(UK);UniversityofMilan(IT);UniversityofOslo(NO);UniversityofStuttgart (DE);WageningenUniversity(NL) 5 CatholicUniversityofLeuven(BE);FinnishInstituteofOccupationalHealth,Helsinki(FI); LundUniversity(SE);NationalandKapodistrianUniversityofAthens(EL);NationalCentre forScientificResearch(CNRS),variouslocations(FR);NationalInstituteforAgricultural Research(INRA),variouslocations(FR);NationalInstituteofPublicHealth,Prague(CZ); SpanishNationalResearchCouncil(CSIC),variouslocations(ES);SlovakMedical University,Bratislava(SK);UniversityofCrete,Heraklion(EL);UniversityofOxford(UK); UniversityofSouthampton(UK) 32 EnvironmentandHealthIssuesAddressedbytheProjectsFunded ENVIRONMENTANDHEALTH ISSUESADDRESSEDBYTHE PROJECTSFUNDED 33 34 EnvironmentandHealthIssues AddressedbytheProjectsFunded GeneralIssues H EALTH AsseeninAnnexB,environmentandhealthprojectsfundedbyFP6addressedavery large number of crosscutting and more targeted issues, some issues being more environmentallyorientedwhereasotherhadtheirfocusonhealth. Inadditiontocarryingoutresearchactivitiesperse,nearlyhalfoftheprojectsalso reviewedstateofthescienceonvariousissues,producingsynopsisreportsorother materials.Examplesofprojectsinclude: 29 x The HENVINET health and environment network, funded through as a coordination action by the Thematic Priority 6, had the ambitious task to provide policy support and to establish a longterm cooperation between researchers, policy makers and other stakeholders in the area of environment andhealthresearchandassessment.The project reviewed, exploited and on disseminated knowledge environmentalhealthissuesbasedonresearchandpractices.Thefourpriority diseases and disorders, broadly defined in the European Environment and Health Action Plan 20042010, were chosen as the topics the project focused on: Asthma and allergies; cancer; neurodevelopmental disorders; endocrine disruptingeffects. 30 x The CAIR4HEALTH support action aimed at strengthening, reviewing and exploiting research results, obtained by Europeanandotherprojectsinthepast,relatedtoairquality andhealthimpacts.Itidentifiedandanalysedtheknowledge gapsandresearchneedsinthefieldofairqualityandhealth, CAIR and the outcomes from the project form a scientifically soundbasistosupporttheEuropeanairqualityandhealthmanagementpolicy development.Someoftheresearchrecommendationsarebeingimplemented 31 by a project called TRANSPHORM , funded by the Seventh Framework Programme. 29 HENVINETHealthandenvironmentnetworkhttp://henvinet.nilu.no CAIR4HEALTHCleanairforhealth–researchneedsforsustainabledevelopmentpolicies www.cair4health.eu 31 TRANSPHORMTransportrelatedairpollutionandhealthimpactsintegratedmethodologies forassessingparticulatematterwww.transphorm.eu 30 35 EnvironmentandHealthIssuesAddressedbytheProjectsFunded x 32 EMFNET , which included 39 participating institutions including WHO, industrial representatives and NGOs, collatedresearchresultsfromEUfundedprojectsandother national and international actions, provided a regular updateonEMFresearchandrelevantinterpretation/advice forthefacilitationofpolicydevelopmentoptionsbytheEU and other bodies. It published more than 40 reports and 20 fact sheets and expert opinions, 4 EMF and health related volumes, and organized and co organized various seminars, workshops and conferences on specific policy relatedEMFandhealthtopics.Theseareavailableontheprojectwebsite. AnumberofprojectsfundedbyFP6madeanefforttoworktowardsharmonisingof methods and approaches to specific issues, and provided guidelines and good practiceexamplesforpotentialendusers.Twoexamples: x A group of 22 European experts on human biomonitoring, coming from national governments, research institutes, industry and nongovernmental organisations in 17 EU member states and Croatia, worked together in the ESBIO 33 coordination action to prepare a coordinated European approach on human biomonitoring. The funding of ESBIO was the first step in a longerterm perspective aimed at developing a coherent approach to human biomonitoring in Europe. The work continues 34 35 throughthefollowupprojectsCOPHES andDEMOCOPHES ,fundedbyFP7 andLIFE+programme,respectively.Thefundingofthisprojectwasthedirect resultoftheAction3 ofEuropeanEnvironmentandHealthActionPlan2004 2010, which called for harmonising human biomonitoring approaches in Europe. 36 x The main objective of the PRONET project was to facilitateexchangeandevaluationofinterventionson environmentandhealthexposurereductionmeasures on a regional level and promote implementation of successful initiatives in other regions of Europe. This PRONET projectfocusedontheexchangeofusefulpracticesin 32 EMFNETEffectsoftheexposuretoelectromagneticfields:fromsciencetopublichealthand saferworkplacehttp://web.jrc.ec.europa.eu/emfnet 33 ESBIO–DevelopmentofacoherentapproachtohumanbiomonitoringinEuropewww.eu humanbiomonitoring.org/sub/esbio.htm 34 COPHESEuropeancoordinationactiononhumanbiomonitoringwww.euhbm.info 35 DEMOCOPHESDemonstrationofastudytocoordinateandperformhumanbiomonitoringon aEuropeanscalehttp://www.euhbm.info/democophes 36 PRONETPollutionreductionoptionsnetworkwww.proneteurope.eu 36 EnvironmentandHealthIssuesAddressedbytheProjectsFunded two areas: (i) the reduction of transportrelated health hazards (air pollution and noise); and (ii) improvement of the indoor environment. As they are key areas in environmental policy the health of the population would benefit significantlyfromexposurereductionmeasures.PRONETsetupaninformation exchange platform for the development of effective and efficient health promotionbased policies and it formed a network of regional authorities and researchersatEuropean,nationalandregionallevel. Many projects funded by FP6 have contributed to building databases and inventoriescontainingdataon,e.g.,specificenvironmentalcontaminants. 37 x The NORMAN network , now established as a permanent selfsustaining network of reference laboratories, research centres and related organisations for the monitoring and biomonitoring of emerging environmental substances, had as its mainmission is to enhance the exchange of information and collection of dataonemergingenvironmentalsubstances.Itcontributedtothedevelopment ofthreedatabases: EMPOMAP: database of leading experts, organisations and projects dealingwithemergingsubstances; EMPODAT: a database of georeferenced monitoring data accompanied byecotoxicologicalinformationfrombioassaysandbiomarkers;contains over8000entries; EMPOMASS:databaseofmassspectrometricinformationonprovisionally identifiedandunknownsubstances. InnovationinFP6projects FP6 projects used innovative approaches to advance knowledge on environment health relationships. Innovation is most evident in the development of methods, toolsandapproachesforenvironmentalandhealthresearchtoadvancethecurrent stateofscienceinvariousaspectsofenvironmentandhealthresearch,includingthe understanding of mechanisms of disease development, and to support evolving policiesandpolicyassessments.Outstandingexamplesinclude: x Methods for combined exposure to chemicals and other environmental stressors: Risk assessment of chemicals is a highly developed discipline, exemplified by a large body of international, regional or national/federal guidelines for the domain of environment and human health. Such guidelines are directed towards the generation of valid and reliable assessment data to helpriskmanagerssetprioritiesandregulationsinthegoalofriskreduction.All 37 NORMANNetworkofreferencelaboratoriesandrelatedorganisationsformonitoringandbio monitoringofemergingenvironmentalpollutantswww.normannetwork.com/index_php.php 37 EnvironmentandHealthIssuesAddressedbytheProjectsFunded guidelines apply to the assessment of single chemicals or of commercial compounds as are present in products. No systematic approach exists for assessing chemical mixtures which are the predominant exposure scenario in 38 the real world. Therefore, the NOMIRACLE project addressed the following major shortcomings that exist within the current assessment approaches: i) they bear on direct effects of single compounds or products;ii)theydealwithuncertaintybyapplying defaultassumptions(‘safetyfactors’)whicharenot strictlybasedonscientificprinciples;iii)theydonot accountformultiplestressorsandindirecteffectsin a dynamic and heterogeneous environment; iv) they typically do not account forcumulative(integratedovertime,space,substances)effects;andv)theydo notallowforsitespecificandotherspatiallydetailedevaluations.Thekeytask of NOMIRACLE has been to meet and overcome such shortcomings, by developing novel methods and an overall conceptual framework for such complex risk assessments. The work has resulted in new tools and methods, scientificfindingsanddraftguidancedocuments.Thenewmethodsarepublicly availableintheNOMIRACLEToolBoxontheprojectwebsite. x Methods for intelligent testing strategies for chemicals: According to the REACH regulation, until 2018, all industrial chemicals with market volumes above1tonneperannumhavetobeevaluatedandacceptedaccordingtothis regulationwithrespecttotheirecotoxicologicalandtoxicologicalprofiles.Itis estimatedthatthiswillconcernca.20000industrialchemicalsinthenext10 years. Integrated testing strategies shift risk assessment from a “boxticking” approachwithextensiveanimaltestingtoamoreefficient,contextspecificand substancetailored approach. The underlying principle is to take advantage of existing information, to group information about similar substances and to integrate exposure considerations. The different and possibly contradictory informationisweighedandtherespectiveuncertaintiestakenintoaccountina WeightofEvidence(WoE)approach.Thusitcombinesallavailabletestingand non testing data and concludes whether or not additional data is needed. In case of data gaps, the intelligent testing strategy proposes the most appropriatemethodtoacquirethemissinginformation.Ideally,withregardto the 3R principle of replacement, reduction and refinement of animal testing, nontesting methods such as in vitro assays and QSAR (qualitative or quantitativestructureactivityrelationships)methodsarepreferredforthis 38 NOMIRACLENovelmethodsforintegratedriskassessmentofcumulativestressorsinEurope http://nomiracle.jrc.ec.europa.eu 38 EnvironmentandHealthIssues AddressedbytheProjectsFunded 39 purpose. Within this perspective, the OSIRIS integrated project developed integrated testing strategiesthatenabletosignificantlyincreasetheuse of nontesting information for regulatory decision making,andthustominimisetheneedforanimaltesting. 40 Onasmallerscale,theCAESAR projectbuiltmodelsto predict toxicity of chemical substances for REACH, using QSARapproaches. x Methods and tools for integrated environmental health impact assessment: 41 42 The HEIMTSA and INTARESE integrated 43 projects, with contributions from the 2FUN project, have developed a general methodology of integratedenvironmentalhealthimpactassessment (IEHIA), from emissions through to health impacts, aggregated via disability adjusted life years (DALYs) and/or via monetary values and that incorporates human health risk assessment as an integral component. The two main projects have elaboratedthatmethodologybydevelopingand working through the full chain approach for application EUwide for many pollutants, and demonstrated its application to the environmental health impact assessment of policies in several sectors, including the complex set of policies and measures to address climate change. The IEHIA methodologydevelopedandproposedhasbeenrelatedtootherapproachesto environmental HIA, e.g., the (modified) DPSEEA framework of WHO, and also situatedwithinthebroaderandmoreencompassingfieldofHIAgenerally.This provides a significant progress beyond the stateoftheart when the projects began. A toolbox was designed to help people design andcarryoutintegratedenvironmentalhealth impact assessments. It is aimed primarily at policymakerswhomaycommissionassessmentsorneedtouse 39 OSIRISOptimizedstrategiesforriskassessmentofchemicalsbasedonintelligenttesting www.osiris.ufz.de 40 CAESARComputerassistedevaluationofindustrialchemicalsubstancesaccordingto regulationswww.caesarproject.eu 41 HEIMTSAHealthandenvironmentintegratedmethodologyandtoolboxforscenario assessmentwww.heimtsa.eu 42 INTARESEIntegratedassessmentofhealthrisksfromenvironmentalstressorsinEurope www.intarese.org 43 2FUNFullchainanduncertaintyapproachesforassessinghealthrisksinfuture environmentalscenarioswww.2fun.org 39 EnvironmentandHealthIssuesAddressedbytheProjectsFunded their results and scientists responsible for conducting assessments. However, it is alsoexpectedtobeusefulforotherstakeholdersinvolvedinassessments,aswellas students who wish to learn about the principles and methods used. The toolbox is available at www.integratedassessment.eu. See also Technical Brief 8: Lessons LearnedandUserAssessmentavailableontheprojectwebsite. x Development of risk/benefit analysis methods for food contaminants: Two 44 45 projects,workingtogetherinacluster,namelyBENERIS andQALIBRA ,were funded,inadditiontoaspecificsupport 46 action BRAFO . The general objective of BENERIS was to create a framework for handling complicated benefitrisk situations, and apply it for analysis of the benefits and risks of certain foods. Thefirstfood commoditytobeusedinthedevelopmentofthe methodology was fish. The main outcomes of BENERIS are improved methodology (open assessment) for benefitrisk assessments, the web workspace Opasnet for performing them in a collaborative way, andtheOpasnetBasedatabasecontaining readytouseinformationneededinassessments.QALIBRA,ontheotherhand, developed a suite of quantitative methods for assessing and integrating beneficial and adverse effects of foods and apply them to selected food groups. The project developed a generalised modular approach to benefit riskanalysisusingmenusofdoseresponseandvaluation functions.Thesecovereddifferenttypesofpositiveandnegativehealtheffects that are commonly encountered in food safety assessment. The benefitrisk analysis methods developed in QALIBRA were implemented in webenabled softwareavailableforusebyallstakeholdersviaanintegratedwebsite. x The use of 'omics' and other approaches for biomarker development: The 25partner 47 NEWGENERIS integrated project investigated maternal exposure during pregnancy to selected carcinogenic and immunotoxic chemicals and evaluatedtheresultingfoetal(inutero)exposureand 44 BENERISBenefitriskassessmentforfood:aniterativevalueofinformationapproach www.qalibrabeneris.eu 45 QALIBRAQualityoflifeintegratedbenefitandriskanalysiswebbasedtoolforassessingfood safetyandhealthbenefitswww.qalibra.eu 46 BRAFOSpecificsupportactiontoinvestigatetheriskbenefitanalysisforfoods www.brafo.org 47 NEWGENERISDevelopmentandapplicationofbiomarkersofdietaryexposuretogenotoxic andimmunotoxicchemicalsandofbiomarkersofearlyeffects,usingmotherchildbirthcohorts andbiobankswww.newgeneris.org 40 EnvironmentandHealthIssuesAddressedbytheProjectsFunded its effects on the foetus and in later childhood, particularly in relation with childhoodcancerandimmunedisorders.Themainresearchtoolemployedby NEWGENERISwasbiomarkers,i.e.,chemicalsorcellularcomponentsmeasured inhumanfluidsortissues,indicativeofexposuretotoxicchemicalsoroftheir early biological effects. For biomarkers of exposure, high throughput techniques were developed. For biomarkers of carcinogenic risk – phenotypic effects, maternal and umbilical cord blood lymphocytes were analysed for micronucleiandmarkersofapoptosis/necrosisandinvitroproliferationrates. For biomarkers of carcinogenic risks genomic effects, new biomarkers were developed, based on the transcriptomic and proteomic signatures of the chemicalsofinterestinmaternalandcordbloodcells.Concerninggenotyping markersofsusceptibility,highthroughputanalysisofpolymorphismsencoding forsusceptibilitypredisposinggeneswascarriedout. 48 The PREDICTOMICS project aimed at developing a novel platform for anticipating liver and kidney chronic toxicity elicited by drugs and xenobiotics. By combining “omics” technologies and advanced cellular models, PREDICTOMICS provided valuable tools for reliable screening of new drugcandidatesbythepharmaceuticalindustry,aswellpotentialtoxins. x x Theuseoftransgenicanimals:Transgenicmiceareoftenusedtostudycellular andtissuespecificresponsestodisease.TheEXERAprojectdevelopednovel3D in vitro models of mouse tissues from five major organs for the pharmaco toxicological analysis of oestrogen receptor interactingcompounds.Theimprovedsystems generatedandexploitedinEXERAcanbeused astoolsforthecharacterisationofnewlysynthesized drugsthatinteractwith nuclear receptors and for the risk assessment of industrial “hormones” (chemicals)thatmaycontaminatethefoodandtheenvironment. Employing largescale environmental epidemiology: In FP6, the European Commission for the first time funded truly largescale environmental epidemiological studies, the best examples being the 49 NEWGENERIS and PHIME integrated projects. NEWGENERIS, already mentioned above under biomarker development, encompassed biobanks representing a total of around 300 000 motherchild pairs, constituting in effect a virtual European birth megacohortwithsubjectscomingfromregionswithawidediversityof 48 PREDICTOMICSShortterminvitroassaysforlongtermtoxicity www.predictomics.com/principal.htm 49 PHIMEPublichealthimpactoflongterm,lowlevelmixedelementexposureinsusceptible populationstratawww.phime.org 41 EnvironmentandHealthIssuesAddressedbytheProjectsFunded environmental conditions and dietary and lifestyle habits. This makes NEWGENERISoneofthelargeststudiesofitskindeverconductedandprovides it with a unique potential to discern the role of foodborne chemicals in the aetiologyofchildhoodcancerandimmunedisease. PHIME has been examining the links between longterm lowlevel exposure toxicmetalsonthenervoussystem(parkinsonism,hearing deficiency, peripheral neuropathy), coronary heart disease (CHD),stroke,osteoporoticfractures,diabetesmellitustype I and II and endstage renal disease. The project has examined thousands of subjects of all ages, including motherchildpairs,fromavarietyofregionsextendingfrom theFaroeIslandstoSeychellesandChina. 42 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Environmentalstressorsaddressed Chemicals Chemicalsbringaboutbenefitsonwhichmodernsociety is entirely dependent, for example, in food production, medicines, textiles, cars etc. They also make a vital contribution to the economic and social wellbeing of citizens in terms of trade and employment. The global production of chemicals has increased from 1 million tonnesin 1930tohundredsof millionsoftonnes.There areabout100000differentsubstancesregisteredinthe EUmarketofwhich10000aremarketedinvolumesofmorethan10tonnes,anda further20000aremarketedat110tonnes.ThechemicalindustryisEurope’sthird largestmanufacturingindustry. However, certain chemicals have caused damage to human health and the environment,resultinginsufferingandprematuredeath.Wellknownexamplesare asbestos,whichisknowntocauselungcancerandmesothelioma,orbenzenewhich canleadtoleukaemia. Thelackofknowledgeabouttheimpactofmanychemicalsonhumanhealthandthe environmenthasbeenacauseforconcernintheEUinthepastcoupleofdecades. For this reason, the Commission has continued supporting research in this area in FP6, following a substantial investment in previous framework programmes. These projectshavethepotentialtosupportnumerousEUpoliciesandinitiatives,suchas Regulation (EC) no 1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH); Council Regulation (EEC)315/93 laying down Community procedures for contaminants in food; Commission Regulation (EC)1881/2006 setting maximumlevelsforcertaincontaminantsinfoodstuffs; EU water policies such as Council directive 98/83/EC on the quality of waterintendedforhumanconsumption; CommunityStrategyforEndocrineDisruptersCOM(1999)706final; CouncilDirectiveontheapproximationofthelawsoftheMemberStates relatingtocosmeticproducts(76/768/EEC) Three Rs (replacement, reduction, replacement) principle in animal experimentation AscanbeseeninFig.3andAnnexC,thelargestnumberofprojectsfundedinFP6 dealt with issues related to environmental chemicals (exposure to chemicals, alternative testing methods, life cycle assessment, health effects etc) (37 projects). 43 EnvironmentandHealthIssuesAddressedbytheProjectsFunded ThusthistrendfollowscloselythatseeninFP5.Itshouldbenoted,however,thatin 50 51 some larger integrated projects (e.g., INTARESE and HEIMTSA ) chemicals were onlyapartofawiderspectrumofenvironmentalstressorslookedatinanintegrated context and not the main focus. Among the chemicals studied, there was a large variety, ranging from heavy metals, cosmetics and persistent organic pollutants to pharmaceuticalproducts. The main objective of the CASCADE Network of Excellence 52 (NoE) was to act as an integrated research network in the field of chemical contaminants in food. Apart from the joint researchprogramme,theprojectdevelopedfromthestartan extensive training and dissemination scheme. The focus of CASCADE scientific activities was to characterise the health implications of exposure to chemicals acting through nuclear receptors. It focused on a limited set of model chemicals, namely dioxin (TCDD), bisphenol A (BPA), vinclozolin and genistein. Reliable health risk assessment information (e.g., toxicities, mechanisms of actions, human exposure levels, data gaps,researchneeds)hasbeenprovidedonTCDD,BPAandvinclozolin. 53 The NORMAN network started its activities in 2005 and it is now established as a permanent selfsustainingnetworkofreference laboratories, researchcentresandrelatedorganisationsforthe monitoring and biomonitoring of emerging environmental substances [defined as defined as substances that have been detected in the environment, but which are currentlynotincludedinroutinemonitoringprogrammesatEUlevelandwhosefate, behaviour and (eco)toxicological effects are not well understood]. Its mission was (andiscontinuing)to(i)enhancetheexchangeofinformationandcollectionofdata on emerging environmental substances; (ii) encourage the validation and harmonisationofcommonmeasurementmethodsandmonitoringtoolssothatthe demands of risk assessors can be better met; and (iii) ensure that knowledge on emerging pollutants is maintained and developed by stimulating coordinated, interdisciplinaryprojectsoncollaborative,problemorientedresearchandknowledge transfertoaddressidentifiedneeds. 50 INTARESEIntegratedassessmentofhealthrisksfromenvironmentalstressorsinEurope www.intarese.org 51 HEIMTSAHealthandenvironmentintegratedmethodologyandtoolboxforscenario assessmentwww.heimtsa.eu 52 CASCADEChemicalsascontaminantsinthefoodchain:ANoEforresearch,riskassessment andeducationwww.cascadenet.org 53 NORMANNetworkofreferencelaboratoriesandrelatedorganisationsformonitoringandbio monitoringofemergingenvironmentalpollutantswww.normannetwork.com/index_php.php 44 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Severallargescaleintegratedprojectswerefundedonadvancingalternativetesting methods for chemicals. In addition to OSIRIS and CAESAR 54 already mentioned previously, projects such as ACUTETOX 55 and REPROTECT were launched, focusing on specific issues and areas where such methods are needed. ACUTETOX undertookthechallenginggoaltocreateanintegratedtesting strategy, which is based exclusively on in vitro and in silico methodstoreplacetheanimaltestingusedtodayforpredicting humanacuteoralsystemictoxicity.REPROTECT,on the other hand, was set up in order to develop/optimise in vitro models that are able to detect adverse effects and mechanisms associated withreproductivetoxicity. Nanoparticles Nanotoxicologyisasubspecialtyofparticletoxicology.Itaddressesthetoxicologyof nanoparticles which appear to have toxicity effects that are unusual and not seen with larger particles. In 2011 the European Commission issued a recommendation to define nanomaterials as materials whose main constituents have a dimension of between 1 and 100 billionth of a metre. The extremely small size of nanomaterials also means that they muchmorereadilygainentryintothehumanbodythanlarger sized particles. How these nanoparticles behave inside the body is still a major questionthatneedstoberesolved. In 2004, the European Commission adopted the Communication 'Towards a European Strategy for Nanotechnology'. While acknowledging European excellence innanosciencesandthepotentialtranslationintocommerciallyviableproductsand processes, it also called for nanotechnology to be developed in a safe and responsible manner. Ethical principles must be adhered to and potential health, safety or environmental risks scientifically studied, also in order to prepare for possibleregulation. Consequently, in 2005, the European Commission adopted the Communication 'Nanosciencesandnanotechnologies:anActionPlanforEurope20052009',defining aseriesofarticulatedandinterconnectedactionsfortheimmediateimplementation of a safe, integrated and responsible approach for nanosciences and 54 ACUTETOXOptimisationandprevalidationofaninvitroteststrategyforpredictinghuman acutetoxicitywww.acutetox.eu 55 REPROTECTDevelopmentofanovelapproachinhazardandriskassessmentorreproductive toxicitybyacombinationandapplicationofinvitro,tissueandsensortechnologies www.reprotect.eu 45 EnvironmentandHealthIssuesAddressedbytheProjectsFunded nanotechnologies, based on the priority areas identified in the abovementioned European Strategy. The Action Plan indicated, inter alia, that the Commission will promote safe and costeffective measures to minimise exposure of workers, consumers and the environment to manufactured nanoscale entities. It will also support a wide range of studies (including epidemiological studies) to (i) evaluate currentandfutureprojectedlevelsofexposure,(ii)evaluatetheadequacyofcurrent approaches to control exposure and (iii) launch appropriate initiatives, propose measuresand/orissuerecommendations. 56 Twoimplementationreportshavebeenpublishedsince2005,thelatestin2009 . Partially as a results of policy initiatives, a new area of study emerged in FP6 with funding of 10 projects (15% of total) (Fig. 3 and Annex C), namely projects dealing with exposure to and impacts of nanoparticles. The EU NanoSafety Cluster is a DG Research and Innovation initiative to maximise the synergies between the existing FP6 and FP7 projects addressing all aspects of nanosafetyincludingtoxicology,ecotoxicology,exposureassessment,mechanismsof interaction, risk assessment and standardisation. Participation in the NanoSafety cluster was voluntary for projects that commenced prior to April 2009, and is compulsory for projects started since April 2009. A detailedcompendium has been publishedontheprojectsfundedbytheThematicpriority3(Nanotechnologiesand nanosciences, knowledgebased multifunctional materials and new production processesanddevices)inFP6. 57 TheoverallgoaloftheNANOSH projectwasto characterise the levels of exposure to specific engineered nanoparticles and to delineate the health effects of selected nanosized particles relevant to the occupational environment. The project developed a strategy for assessingexposuretoengineerednanoparticlesinarangeofworkplacesaswellasa decision logic for determining whether workers were likely to be exposed to these particles. Most nanoparticles were able to damage DNA in vitro, and, for titanium oxide,thisseemedtobeduetoprimaryoxidativeDNAdamage.Somenanomaterials werealsocapableofincreasingchromosomedamageinvitro,zincoxideshowingthe clearesteffect. Otherfundedprojectsaredescribedinthecompendiummentionedintheprevious paragraph. 56 http://ec.europa.eu/nanotechnology/policies_en.html NANOSHInflammatoryandgenotoxiceffectsofengineerednanomaterials www.ttl.fi/partner/nanosh 57 46 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Ambientairpollution Air pollution is the environmental stressor that the largest number of European citizens are exposed to in their daily activities. The issue of air quality is still a major concern for manyEuropeancitizens.Itisalsooneoftheareasinwhichthe European Union has been most active. Since the early 1970s, theEUhasbeenworkingtoimproveairqualitybycontrollingemissionsofharmful substances into the atmosphere, improving fuel quality, and by integrating environmental protection requirements into the transport and energy sectors. European Union policy on air quality aims to develop and implement appropriate instruments to improve air quality. The control of emissions from mobile sources, improving fuel quality and promoting and integrating environmental protection requirementsintothetransportandenergysectorarepartoftheseaims. The objective considered in the EU Sixth Environment Action Programme 2002 58 2012 istoachievelevelsofairqualitythatdonotgiverisetounacceptableimpacts on, and risks to, human health and the environment. The Community is acting at manylevelstoreduceexposuretoairpollution:throughEClegislation,throughwork at the wider international level in order to reduce crossborder pollution, through working with sectors responsible for air pollution and with national, regional authoritiesandNGOs,andthroughresearch. 59 The EU Thematic Strategy on Air Pollution states that even with full implementation of existing laws, environment and health problems will persist in 2020ifnofurtheractionistaken.ItisestimatedthatcurrentlyintheEUthereisa lossinlifeexpectancyofover8monthsduetoPM 2.5 inair,equivalentto3.6million lifeyearslostannually.Expressedinmonetaryterms,thedamagetohumanhealthis estimatedtobebetween€189609billionannually. Many projects were funded on exposure to and health impacts of air pollution in 60 FP5 .Perhapsdue tothis,FP6sawapauseinfundingoftargetedprojectsonthis issue. Although 16 projects funded were focused to some extent on ambient air 61 pollution as a stressor, only one support action (CAIR4HEALTH ) had as its main focus air pollution (Fig. 3 and Annex C). In other projects, air pollution was one aspectfocusedinwithintheframeworkofalargerstudy. 58 SixthEnvironmentActionProgrammeEnvironment2010:Ourfuture,Ourchoice http://ec.europa.eu/environment/newprg 59 http://europa.eu/legislation_summaries/environment/air_pollution/l28159_en.htm 60 http://ec.europa.eu/research/environment/themes/projects_en.htm 61 CAIR4HEALTHCleanairforhealth–researchneedsforsustainabledevelopmentpolicies www.cair4health.eu 47 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Asithasbecomeclearerthatoutdoorairpollutionat‘normal’levelshasanadverse impactonpopulationhealth,policymakers,researchersandotherswereinterested in understanding how big this effect might be. This has led to the development of methods and tools attempting to answer two related kinds of questions: (i) One (‘burden of disease’) question focused on the mortality and morbidity impacts of current concentrations of air pollution; (b) Another (‘health impact assessment’) question focused on the mortality and morbidity effects of changing air pollution levels,andsometimesalsoonthewiderhealthimpactassessment(HIA)ofpolicies and measures designed to reduce outdoor air pollution. Within this context, the 62 mainaimsofthe HEIMTSA OutdoorAirCaseStudy were (using baseline scenarios for the years 2020, 2030 and 63 2050) were to extend the methodology of CAFE in order to provide a methodology for HIA of outdoor air pollution acrossthefullimpactchain. Transport is an essential component of modern life and may both improve and deteriorate public health. Main problems related to transport are air pollution, climate change, water and soil pollution, transport accidents and injuries, traffic noise, physical inactivity, psychological and social effects, but also problems as the 64 use of fossil fuels, the loss of public space/land/natural habitats etc. INTARESE evaluated the health benefits of alternative transport scenarios and measures. The general INTARESE methodology was applied to policies in five cities spread over Europe to reduce problems related to motorized traffic. The INTARESE methodology can be characterized as an integrated environmental health impact assessment. The conclusions were, among others that: (i) For the individuals who shift from car to bicycle, we estimated that beneficial effects of increased physical activity are substantially larger than the potentialmortalityeffectofincreasedinhaledairpollutiondosesandtheincreasein traffic accidents; (ii) The policies in Rome and London resulted in PM10 and NO2 emission decreases of about 30% (at street level) and 10% (city average level) respectively;(iii)Consistentwiththemodestchangeinairpollutionconcentrations, thepoliciesinRome,theHagueandLondonresultedinsmallgainsinlifeexpectancy andasmallreductioninthenumberofhospitaladmissions,whenexpressedatthe city area level. More information is available in the Technical Brief 5 'Integrated AssessmentsofWasteandTransport'issuedbytheproject. 62 HEIMTSAHealthandenvironmentintegratedmethodologyandtoolboxforscenario assessmentwww.heimtsa.eu 63 TheCleanAirforEurope(CAFE)Programme:TowardsaThematicStrategyforAirQuality http://ec.europa.eu/environment/archives/cafe/general/keydocs.htm 64 INTARESEIntegratedassessmentofhealthrisksfromenvironmentalstressorsinEurope www.intarese.org 48 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Indoorairpollution People spend 60 – 90 % of their life indoors – be it at home or in other public or privateindoorenvironments,suchasschools,cafésandrestaurants.Havingcleanair indoors is very important for the health of the population as a whole and it becomes particularly groupslikebabies,children important for vulnerable and the elderly or people already suffering from, e.g., respiratory or allergic diseases. The health effects of "cocktails" of differentindoorpollutants, their concentrations and their public health significance are being studied worldwide. Already today, for many pollutants, scientific evidenceshowsaseriousimpactonthehealthofthepopulation.Variousindoorair pollutants are responsible for or exacerbate respiratory diseases, allergies, intoxication and certain types of cancer (e.g., asbestos, radon, environmental tobacco smoke (ETS), combustion products, volatile organic compounds, biological pollutantsetc.). In the past ten years, EU has started to attach more importance to the issue of indoorairquality.Oneconsequenceofthiswastheinclusionofaspecificactionon improvingindoorairqualityintotheEuropeanEnvironmentandHealthActionPlan. ThishasalsoresultedatpracticallevelintheestablishmentofanEUExpertGroupon Indoor Air Quality by European Commission's Health and Consumer's Directorate General, which has organised several meetings on this issue. These meetings have gatheredrelevantstakeholders(includingtheENVIEprojectseebelowandWHO) todiscussfurtherdirectionsandpolicyactionsinthisarea.Indoorairqualityislikely to continue being an issue of importance for policy makers, especially in view of implementingtheDirectiveontheenergyperformanceofbuildings,whichwillhave animpactonindoorairqualityandwellbeingofpeople. 65 The aim of the ENVIE coordination action was to increase the understanding of the Europewide public health impacts of indoor air quality by identifying the most widespread and significant indoor causes for these health impacts and evaluating the existing and optional building and housingrelated policies for controlling them. The project organised a wellattended enduser workshop. It produced four comprehensive policyrelevant reports (Health Effects; Indoor Air Pollution Exposure; Characterisation of Spaces and Sources; Policies on Ind oor Air Quality:AssessmentandNeeds),whichareavailableontheprojectwebsite. 65 ENVIE Coordination action on indoor air quality and health effects www.envie iaq.eu/home.html 49 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Noise Although now acknowledged as being an increasingly important environmental stressor,therewerenonoisefocusedtargetedprojectsfundedinFP6.Thesemaybe due to the fact that this issue was not identified amongst the highest priorities by the European Environment and 66 Health Strategy in 2004. Nevertheless, the HEIMTSA and 67 INTARESE integrated projects, included noise as a factor when developing a general methodology of integrated environmental health impact assessment (IEHIA). HEIMTSA in particular published a noise case study (Integrated environmental health impact assessment for noise due to urban road traffic), available on the project website. The reportcalculatedfromtheexposuredistributionsthehealth impact of noise for annoyance, sleep disturbance, and myocardial infarction. The health impact was also expressed in burden of disease and damage costs: for the year2050thenumberofdisabilityadjustedlifeyearslostduetourbanroadtraffic noisewasfoundtobe1.6millionandthedamagecosts14billionEuros. Nonionisingradiation Due to the funding of several projects in FP5 on the health 68 effects of electromagnetic fields (EMF) , which continued during the FP6 period including analyses of results, no new research projects were financed during this period. Nevertheless, the Commission monitored closely activities in thisfieldasaresultofthespecificaction'Followdevelopments regardingelectromagneticfields'intheEuropeanEnvironment andHealthActionPlan. InlinewiththeEUTreaty,itistheresponsibilityoftheMemberStatestoprotectthe healthofthepublicand,inparticular,totakedecisionsandmeasuresregardingEMF exposure levels. However, EU regulators felt the need to provide a common protective framework for the EU population. The purpose was to help Member Statesputcoherentandcomparableexposurelimitsinplace.ThisledtheEuropean Council to adopt in 1999 the Council Recommendation on the limitation of the 66 HEIMTSAHealthandenvironmentintegratedmethodologyandtoolboxforscenario assessmentwww.heimtsa.eu 67 INTARESEIntegratedassessmentofhealthrisksfromenvironmentalstressorsinEurope www.intarese.org 68 http://ec.europa.eu/research/environment/themes/projects_en.htm 50 EnvironmentandHealthIssuesAddressedbytheProjectsFunded 69 exposureofthegeneralpublictoelectromagneticfields(0Hzto300GHz) .Thisnon bindingtextservedastheframeworkofreferenceforthedevelopmentofotherEU 70 legislation,especiallyDirective2004/40/EC3ontheexposureofworkerstoEMF ,as 71 wellasDirectives1999/5/EC4onradioandtelecomsequipment (alsoknowasthe 72 R&TTE Directive) and 2006/95/EC5 relating to certain electrical equipment (also knowastheLowVoltageDirective). AscalledforbytheCouncilRecommendationmentionedabove,theCommissionis keeping 'the matters covered by this recommendation under review'. So far, the Commissionhasrequestedfourindependentscientificassessmentsofthevalidityof theexposureguidelinestomakesuretheyprovideahighlevelofprotectiontothe public, the most recent ones having been published in 2007 and 2009 by the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR). To date,theseassessmentshavenotidentifiedanyscientificrationalethatcouldleadto arevisionoftheexposurelimits. Within the context of reviewing scientific evidence, the 73 Commission funded in FP6 the EMFNET coordination action with39participatinginstitutions,theaimofwhichwastocollate and analyse research results from EU funded projects and other national and international actions, provided a regular update on EMF research and relevant interpretation/advice for the facilitationofpolicydevelopmentoptionsbytheEUandotherbodies. Itpublishedmorethan40reports(examples:reportonepidemiologicalstudies;on healtheffectsofRFwithrecommendationsfornonionisingradiationprotectionand research needs; on inventory of EMF research in Central European countries; on laboratory studies on ELF fields etc.) and 20 fact sheets and expert opinions (e.g., Comments on the BioInitiative working group report; Fact sheet on exposure to shortrange wireless technologies; Fact sheet on health risk posed by high voltage powerlines etc.),fourEMFandhealthrelatedvolumes,andorganisedandco 69 CouncilRecommendationof12July1999onthelimitationofexposureofthegeneralpublicto electromagneticfields(0Hzto300GHz),OfficialJournaloftheEuropeanUnionL199,pp5970, 30.7.1999. 70 Directive2004/40/ECoftheEuropeanParliamentandoftheCouncilof29April2004onthe minimumhealthandsafetyrequirementsregardingtheexposureofworkerstotherisksarising fromphysicalagents(electromagneticfields),OfficialJournaloftheEuropeanUnionL184,pp1 9,24.5.2004 71 Directive1999/5/ECoftheEuropeanParliamentandoftheCouncilof9March1999onradio equipment and telecommunications terminal equipment and the mutual recognition of their conformity,OfficialJournaloftheEuropeanUnionL91,pp1028,7.4.1999 72 Directive2006/95/ECoftheEuropeanParliamentandoftheCouncilof12December2006on theharmonisationofthelawsofMemberStatesrelatingtoelectricalequipmentdesignedfor usewithincertainvoltagelimits(codifiedversion)(TextwithEEArelevance),OfficialJournalof theEuropeanUnionL374,pp1019,27.12.2006 73 EMFNETEffectsoftheexposuretoelectromagneticfields:fromsciencetopublichealthand saferworkplacehttp://web.jrc.ec.europa.eu/emfnet 51 EnvironmentandHealthIssuesAddressedbytheProjectsFunded organised various seminars, workshops and conferencesonspecificpolicyrelatedEMFand health topics. Materials produced by the project are available on the project website. Some of the work continues under the 74 auspicesoftheEFHRAN project. Microbialagents Water is life! It is a precondition for human, animal and plant life as well as an indispensable resource for the economy. Water also plays a fundamental role in the climate regulation cycle. Protection of water resources, of fresh and salt water ecosystemsandofthewaterwedrinkandbatheinistherefore oneofthecornerstonesofenvironmentalprotectioninEurope. In2000,theEuropeanUniontookagroundbreakingstepwhen itadoptedtheWaterFrameworkDirective(WFD).Itintroduces a new legislative approach to managing and protecting water, based not on national or political boundaries but on natural geographicalandhydrologicalformations:riverbasins.Italsorequirescoordination ofdifferentEUpolicies,andsetsoutaprecisetimetableforaction,with2015asthe targetdateforgettingallEuropeanwatersintogoodcondition. The WFD is a framework for EU water policy and is complemented by other legislation regulating specific aspects of water use. These include (i) The Groundwater Directive (2006); (ii) The Environmental Quality Standards Directive (2008); (iii) The Urban Wastewater Directive (1991); (iv) The Nitrates Directive (1991);(v)ThenewBathingWaterDirective(2006);(vi)TheDrinkingWaterDirective (1998); (vii) The Floods Directive (2007); (viii) The Marine Strategy Framework Directive(2008). The2006BathingwaterDirective(the"new"Directive,repealingby2014the"old" 1976BathingWaterDirective)hasthepurposetopreserve,protectandimprovethe quality of the environment and to protect human health. The provisions of the Directive include a number of obligations for Member States, as well as rules generallyapplicableallacrosstheEU. WithintheframeworkoftheDrinkingWaterDirective,atotalof48microbiological andchemicalparametersmustbemonitoredandtestedregularly. 74 EFHRANEuropeanhealthriskassessmentnetworkonEMFexposurehttp://efhran.polimi.it 52 EnvironmentandHealthIssuesAddressedbytheProjectsFunded 75 EPIBATHE wasfundedasapolicysupportingproject because of the relative paucity of EU data describing the health effects of bathing in EU freshwaters and Mediterranean marine waters. Both environments provide important recreational resources throughout the Union. The provided new information to underpin the WHO Guidelines for recreational waters published in 2003.Thisinformation,togetherwithnewdatafortheUSA,hasbeenevaluatedby WHOinJanuary2009duringanexpertconsultationtoconsiderrevisionoftheWHO GuidelinesinthisareafromwhichelementsoftheEUBathingWaterDirective(2006) criteria derive. The project did not produce a clear evidencebase which would suggestthatarevisionofthewaterqualitycriteriaoutlinedinAnnex1ofthe2006 Bathing Water Directive should be undertaken. The risks attributable to bathing in freshwaterswerelessmarkedthaninmarinewaterenvironments.Thissuggeststhat a differential in standards applied to both environments, as is evident in the 2006 BathingWaterDirective,issupportedbytheavailableandnewlyderivedevidence. 76 VIROBATHE aimed to provide a procedure for analysis of EU bathing waters for noroviruses and adenoviruses by validated comparisonsofmethodsforprocessingwatersamplestoachieve thebestvirusrecoveryconsistentwithcostandfeasibilityofuse 77 in routine monitoring laboratories. HEALTHY WATER , on the otherhand,advancedourknowledgeonpathogenesis ofemergentmicrobialpathogensindrinkingwaterto understandtheirtransmissiontohumans.Theproject focused on all major types of pathogens, i.e., viruses, bacteria and protozoa, and concentrated on a representativesetofEuropeandrinkingwatersupplysystemsandsourcewatersof specificsensitivitytohumanhealth. 78 The HIWATE project investigated potential human health risks associated with longterm exposure to low levels of disinfectants (such as chlorine)anddisinfectantbyproductsoccurringinwaterforhumanconsumption 75 EPIBATHEAssessmentofhumanhealtheffectscausedbybathingwaters http://ec.europa.eu/research/fp6/ssp/epibathe_en.htm 76 VIROBATHEMethodsforthedetectionofadenovirusesandnorovirusesinEuropeanbathing waterswithreferencetotherevisionoftheBathingWaterDirective76/160/EEC www.virobathe.org 77 HEALTHYWATERAssessmentofhumanhealthimpactsfromemergingmicrobialpathogensin drinkingwaterbymolecularandepidemiologicalstudieswww.helmholtz hzi.de/en/healthy_water 78 HIWATEHealthimpactsoflongtermexposuretodisinfectionbyproductsindrinkingwater www.hiwate.eu 53 EnvironmentandHealthIssuesAddressedbytheProjectsFunded and use in the food industry. The study comprised riskbenefit analyses including quantitativeassessmentsofriskassociatedwithmicrobialcontaminationofdrinking waterversuschemicalriskandcomparedalternativetreatmentoptions. Climatechange A crosscutting and previously little funded issue that emergedinFP6istheimpactofclimatechangeonhealth. Eight projects were funded, reflecting the increasing importanceofclimatechangeasanissueingeneralandthe lack of data as regards health impacts in particular, as identified in the 3rd IPCC (Intergovernmental Panel on ClimateChange)report.Itshouldbenoted,however,thatallbutoneoftheprojects 79 (EDEN ),didnothavetheirmainfocusonthehealthimpacts. EDEN identified and evaluated European ecosystems and environmental conditions linked to global change, which can influence the spatial and temporal distribution and dynamics of pathogenic agents. It worked on providing predictive emergence and spread models including global and regional preventive, early warning, surveillance, and monitoring tools andscenarios.Diseaseswereselectedaccordingtothevectors andhostsinvolvedintheirepidemiology:tickborneencephalitis,haemorrhagicfever with renal syndrome (rodents), leishmaniasis (sandflies), West Nile and malaria (mosquitoes). Also, African sources of West Nile and Rift Valley fever viruses were studiedtoimprovecontrolforthebenefitofAfricanpopulations,andinvestigatethe risk of introduction in Europe. The results show, in general, climate change alone cannotexplaintheupsurgeoremergenceofvectorbornediseasesinEurope.This was demonstrated for the case of tickborne encephalitis in Baltic countries and CentralEurope,forwhichsocioeconomicalfactors(poverty)andhumanbehaviour aretightlyrelatedtothediseaserisk.Partsof the activities continue in EDENext, a project th funded by the 7 Framework Programme of theEU. 80 81 TheHEIMTSA andINTARESE integratedprojectshadasoneoftheirobjectivesto test the integrated environmental health impact assessment system (IEHIAS) and apply the INTARESE/HEIMTSA methodology to a realistic policy scenario. The so calledcommoncasestudywasthemeanstofulfilthismainobjective.Thecommon 79 EDENEmergingdiseasesinachangingEuropeanenvironmentwww.edenfp6project.net HEIMTSAHealthandenvironmentintegratedmethodologyandtoolboxforscenario assessmentwww.heimtsa.eu 81 INTARESEIntegratedassessmentofhealthrisksfromenvironmentalstressorsinEurope www.intarese.org 80 54 case study addressed the fact that policies and measures for mitigation of and adaptiontoclimatechangearenearlyalwayschosenwithafocusonthereductionof CO2eqandthecostofthemeasures.However,theremayberelevantsidebenefits ordamages,e.g.,decreaseorincreaseinhealthimpacts,whichshouldalsobetaken intoaccountduringthedecisionprocess.Thusthecasestudyaddressed,interalia, thefollowingquestion:whatarethe(negativeorpositive)healthimpactsofclimate change policies in Europe for the years 2020, 2030, and 2050? The results show that the impact of most climate change mitigation policies on environmental human health is nearly as important as the climate change effects themselves. Taking health impacts into account when making decisions about climate protection will change the cost benefit ratio and the ranking of policies considerably. It is thus obvious that any decision support in the field of climate protectionshouldbeaccompaniedbyanintegratedhealthimpactassessment.Quite some climate protection policies have important positive effects, i.e., they reduce healtheffectsconsiderably.Howeversomepolicies,especiallybiomassburningand reducingairexchangeratesinhouses,causequitehighadditionalhealthimpacts. 55 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Fig.3 Environmentalstressorsaddressedbytheprojects:Numberofprojectsfunded Environmental factors and issues addressed by projects 45 42 40 35 30 25 nb of projects 20 16 15 10 9 10 8 8 3 5 1 ts ev en e ex tre m ns ,w as te EM F, UV , no ise , Al le rg e ch an g e ts lim at e C In d oo ra ia lp ir p at ol lu ho g en ta n s s rti cl e pa M ic ro b an o N Am bi en ta ir C po he m llu ta n ica l s ts 0 56 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Healthendpointsstudied When analysing the health endpoints and diseases investigated in FP6 projects, it becomes evident that the project portfolio comprised mostly projects focusing on 82 83 several endpoints concurrently (e.g., PHIME or ATHON ), although a few 84 85 addressed a single endpoint or disease (e.g., GABRIEL or ECNIS ; 'onedisease' projectsarenotthenormintheenvironmentandhealtharea(AnnexD). Cancer,genotoxiceffects: Numerous factors found in the environment are known to cause or are likely to cause cancer in humans. They include tobacco, ultraviolet radiation, fibres, fine particles, and dust, and chemicals such as pesticides, dioxins, and benzidine. It is estimatedthatasmanyastwothirdsofallcancercasesarelinkedtoenvironmental causes. Many of these are linked to modifiable lifestyle factors such as smoking or physicalinactivity. The European Environment and Health Strategy aimed in its first cycle from 2004 2010 to establish a good understanding of the link between childhood respiratory diseases, asthma and allergies; neurodevelopment disorders; childhood cancer; as wellasendocrinedisruptingeffects.Thistranslatedintoaspecificresearchactionin the European Environment and Health Action Plan, namely Action 6 Targeting researchondiseases,disordersandexposures.Amongstthesubobjectiveswasthe development of European networks to promote research into uncommon cancers, the identificationof geneenvironment interactions involved in the development of cancerinhighriskpopulations,andthedefinitionofpreventionstrategies. As seen in Annex D, the largest number of FP6 projects was focused on genotoxic/mutageniceffectsandcancer. 82 PHIMEPublichealthimpactoflongterm,lowlevelmixedelementexposureinsusceptible populationstratawww.phime.org 83 ATHONAssessingthetoxicityandhazardofnondioxinlikePCBspresentinfood www.cascadenet.org/~athon 84 GABRIELMultidisciplinarystudytoidentifythegeneticandenvironmentalcausesofasthmain theEuropeancommunitywww.gabrielfp6.org 85 ECNISEnvironmentalcancerrisk,nutritionandindividualsusceptibilitywww.ecnis.org 57 EnvironmentandHealthIssuesAddressedbytheProjectsFunded 86 AsaresultoftheAction6,theNEWGENERIS integrated project (described previously, focusing on childhood cancerandimmunedysfunction)andtheECNISNetwork of Excellence were funded. ECNIS brought together European research groups from 25 institutions of 13 countries into a durable network of partners to conduct cuttingedge research on cancercausationandprevention.ThevisionofECNISwasthecreationofadynamic researchnetworkwhichaimedtodecreasecancerincidencebyidentifyingchemicals orotherfactorsintheenvironmentandfoodwhichcausecancer,byelucidatingthe mechanismsbywhichdietaryandlifestylepatternsincreaseordecreasecancerrisk, byfacilitatingthedevelopmentofnewfoodswithcancerpreventiveproperties;by discovering genetic (hereditary) factors, which make individuals more or less susceptible to cancer; and by formulating improved approaches to the risk assessmentofcarcinogens. 87 The major goal of the CARCINOGENOMICS projectwastodevelopaseriesofmechanism based in vitro tests that are representative of various modes of carcinogenic action for a number of major target organs for carcinogenicaction,e.g.,liver,lungs,andkidneys.Ithasalsotheobjectiveofbuilding aniterativeinsilicomodelofchemicalcarcinogenesis. Neurodevelopmentalandimmuneeffects AnothersubobjectiveofAction6mentionedintheprevioussectionwastosupport research on the causes and mechanisms of neuroimmune disorders, identifying genetic and environmental risk factors. Neurodevelopmental disorders result from impairmentsofgrowthanddevelopmentofthebrainandnervoussystemandlead tomanydisorders.Thesemechanismscanbeinfluencedbyenvironmentalfactors. Thenervousandimmunesystemshavemanyinteractionsthatdictateoverallbody health. 86 NEWGENERISDevelopmentandapplicationofbiomarkersofdietaryexposuretogenotoxic andimmunotoxicchemicalsandofbiomarkersofearlyeffects,usingmotherchildbirthcohorts andbiobankswww.newgeneris.org 87 CARCINOGENOMICSDevelopmentofahighthroughputgenomicsbasedtestforassessing genotoxicandcarcinogenicpropertiesofchemicalcompoundsinvitro www.carcinogenomics.eu 58 EnvironmentandHealthIssuesAddressedbytheProjectsFunded 13 FP6 projects addressed some aspects of neurodevelopment in their work plans (Annex D). A further 7 projects looked at some 88 aspectsofeffectsontheimmunesystem.DEVNERTOX focusedon generating experimental models to improve developmental neurotoxicity testing and risk assessment for neurotoxic food contaminants (methylmercury and two PCBs: PCB153 and PCB126). Theresultsindicatethatthecombineduseofinvitroandinvivomethodologiesisa successful strategy to identify neurodevelopmental toxicity and characterize the mechanisms of actions of potentially neurotoxic substances. The analysis of behaviourisafirstchoiceapproachtodetectsubtleandlonglastingmodificationsin vivo.Learningandmemoryfunctionswereimpairedinbothratsandmice. Reprotoxiceffects One of the main aims of the European Environment and Health Strategy was to further our understanding of endocrinedisrupting effects. According to the International Programme for Chemical Safety, endocrine disrupters are exogenous substances that alter function(s) of the endocrine system and consequently cause adversehealtheffectsinanintactorganism,oritsprogeny,or(sub)populations.The most frequently studies effects are those related to the reproductive system (e.g., decreased semen quality, increased time to pregnancy or risk of development of testicularcancer). InadditiontothepreviouslydescribedCASCADENetworkofExcellencewithspecific focustorestructureresearchinEuropeonendocrinedisruptingchemicals,10other projects were funded with at least some relevance to the endocrine disruptingissue(AnnexD).Amongstthese,therewastheFOODAND 89 FECUNDITY project looking from various points of view at pharmaceuticals with a potential to affect human fecundity via exposurethroughthehumanfood chain, and the previously 90 mentioned REPROTECT integrated project developinginvitromodelsabletodetectadverseeffectsandmechanismsassociated withreproductivetoxicity. 88 DEVNERTOXToxicthreatstothedevelopingnervoussystem:invivoandinvitrostudieson theeffectsofmixtureofneurotoxicsubstancespotentiallycontaminatingfood www.imm.ki.se/devnertox 89 FOODANDFECUNDITYPharmaceuticalproductsashighriskeffectors http://foodandfecundity.factlink.net 90 REPROTECTDevelopmentofanovelapproachinhazardandriskassessmentorreproductive toxicitybyacombinationandapplicationofinvitro,tissueandsensortechnologies www.reprotect.eu 59 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Respiratorydiseases,allergy/asthma: There are over 100 million people with asthma, allergy and chronic obstructive pulmonary disease (COPD) in Europe. Over 80 million people in Europe have some form of allergic disease and their prevalence is increasing. Allergic diseases are a continuum from the atopic eczema and allergic rhinitis to asthma. In certain cases foodallergyisariskfactorforthedevelopmentofasthma.This'allergicmarch'isa challenge for healthcare systems. Approximately 300 million people around the world have asthma, and it has become more common in both children and adults globally in recent years. Estimates have shown that the number of people with asthmacouldgrowtoasmanyas400450millionpeopleworldwideby2025.Around 30millionpeopleinEuropehaveasthma,andasmanyas6millionsuffersymptoms whicharecharacterisedassevere. In view of this alarming picture, the European Environment and Health Strategy urgedtheEuropeanCommissiontosupportresearchonthe causes of asthma and allergy focusing on complex interactions, such as changes in the environment and lifestyles. As a result, 11 projects were funded touching uponsomeaspectsofthisissueinFP6(AnnexD).Perhaps 2 91 the most wellknown one was the GA LEN network of Excellence.ItwascreatedtocombatfragmentationintheEuropean researcharea, ensuring excellence in EU allergy and asthma research by bringing together institutionsandresearchersfromacrosstheEU.Oversevenyearslater,thevisionof GA²LENisstilltoreducetheburdenofallergicdiseasesinEuropebyimprovingthe health of European with allergic diseases, increasing the competitiveness and boostingtheinnovativecapacityofEUhealthrelatedindustriesandbusinesseswhile addressing health issues including emerging allergies. Work carried out by GA²LEN has established the EU as a leader in the field of allergy and asthma research and clinicalcare. 91 GA2LENGlobalallergyandasthmaEuropeannetworkwww.ga2len.net 60 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Infectiousdiseases SixprojectsfundedbyFP6werefocusedonthespreadofinfectiousdiseasesinthe environment (Annex D). In addition to the projects already described above under 'Microbial agents' and 'climate change' (EDEN, EPIBATHE, HEALTHY WATER), two largescaleintegratedprojectsfocusingonclimatechangehadasmallpartonhealth impacts,focusing,amongstothers,ontheriskofspreadofinfectiousdiseases. 92 ENSEMBLES concluded,interalia,thatclimatevariability, as characterised by extreme weather events and interannualvariability,isknownto affectcertaininfectious diseases. The impacts of longterm shifts in climate conditionsmayleadtoshiftsinthedistributionofinfectious diseases and areas suitable for food production. The impacts on health will outweigh the benefits, and populations in lowincome countriesarelikelytobeworstaffected.Methodsforestimatingthehealtheffectsof climate change are at an early stage of development. The project developed empricialstatistical models were developed to estimate the direct impact of daily temperature on respiratory and cardiovascular mortality (the direct effects of heat and cold) and on diarrhoeal disease mortality, based on observational studies of exposureresponsefunctions. 93 CIRCE , on the other hand, had a part on human health aiming at identifying and assessing selected health impacts of climate change in the Mediterranean. Several countries conductedhealthimpactassessmentsofclimate change. From these studies and assessments, it canbeexpectedthatprojectedtrendsinclimate changerelated exposures of importance to humanhealtharelikelytoincreaseinheatwave, drought and firerelated health impacts, change infoodbornediseasepatterns,changeinthedistributionofinfectiousdiseasesand potentially contributing to the establishment of tropical and subtropical species, increaseintheburdenofwaterbornediseasesandwaterstress,andincreaseinthe frequencyofrespiratorydiseasesandallergicdisorders. 92 ENSEMBLESEnsemblebasedpredictionsofclimatechangesandtheirimpacts www.ensembleseu.org 93 CIRCEClimatechangeandimpactresearch:theMediterraneanenvironment www.circeproject.eu 61 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Otherendpoints: Inadditiontothemajorhealthimpactsandendpointsdescribed above,otheraspectswerealsocovered(AnnexD).Someprojects lookedatcardiovasculardisease,metabolicdisorders,obesity, diabetes,andstroke,althoughtherewasnotanytargetedproject ontheseendpoints.Asmallnumberofprojectsalsofocusedon hepatic,renalandbonetoxicityaswellasgeneralmortalitytrends. 62 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Conclusions Taken globally, it can be concluded that the projects funded by FP6 have had an impactonmanyfronts,whichhasfrequentlyhavealonglastingeffectswellbeyond thelifetimeoftheproject. Examplesofimpacts: Many projects endeavoured to establish the current state of science in a particulardomainofenvironmentalhealthsciences(e.g.,EMFNETcollatedand analysed research results from EU funded projects and other national and internationalactionsonhealthrisksofexposurestoelectromagneticfields) The vast majority of projects advanced the state of the environment and health sciences, and some took innovative steps to accomplish this (e.g., NEWGENERIS, a project focused on childhood cancer and immune disorders, carriedoutexperimentalstudiestodevelopandvalidatenewbiomarkersand highthroughput analytical methodologies, including in vitro studies to assess effectsofenvironmentalcontaminantsonsperm,transplacentaltransportand metabolism,inordertoidentifynewrelevantbiomarkers) NewfundinginstrumentsintroducedinFP6allowedto advancethebuildingofaEuropeanResearchAreain some specific domains of environmental health 2 sciences (e.g., the GA LEN network of Excellence was created to combat fragmentation in allergy/asthma research in Europe, ensuring excellence in EU allergy andasthmaresearchbybringingtogetherinstitutions andresearchersfromacrosstheEU) Partially thanks to major policy initiatives taken during the course of FP6, projects were funded to tackle emerging issues (e.g., the EU NanoSafety Clusterwasinitiated,includingseveralFP6projects,tomaximisethesynergies betweentheexistingFP6andFP7projectsaddressingallaspectsofnanosafety including toxicology, ecotoxicology, exposure assessment, mechanisms of interaction,riskassessmentandstandardisation) Many projects funded have the potential to provide support to EU policies including ones where there is no EU legislation yet (e.g., ENVIE aimed to increasetheunderstandingoftheEuropewidepublichealthimpactsofindoor airquality,notyetregulatedintheEUinthesamewayasoutdoorairpollution, by identifying the most widespread and significant indoor causes for these health impacts and evaluatingthe existing and optional building and housing relatedpoliciesforcontrollingthem) 63 EnvironmentandHealthIssuesAddressedbytheProjectsFunded Manyprojectsbuiltdatabases,tools,methodsandmodelsthatcanbeusedby otherprojectsandstakeholdersinthefuture(e.g.,NORMANdevelopedthree databases, one of which contains georeferenced chemical monitoring data accompaniedbyecotoxicologicalinformationfrombioassaysandbiomarkers) 64 ProjectData PROJECTDATA 65 CHAPTERIProjectsFocusedonCoordination,Harmonisation,Networking,PolicySupport CHAPTERI Projectsfocusedoncoordination, harmonisation,networking, policysupport 67 68 CONTRACTNUMBER:502173 PROJECTTYPE:Coordinationaction TOTALPROJECTCOST:€2269394 ECCONTRIBUTION:€1534994 STARTINGDATE:March1,2004 ENDDATE:August31,2008 DURATION:54months EMFNET EFFECTSOFTHEEXPOSURETO ELECTROMAGNETICFIELDS:FROMSCIENCE TOPUBLICHEALTHANDSAFERWORKPLACE Summary: Research on possible health implications of exposure to electromagnetic fields (EMF) has been carried out by a numberofresearchcentres,laboratoriesanduniversities, supported by international, national and industrial funding bodies. Due to the extent and diversity of researchactivitiesbeingundertaken,itisusuallydifficult to provide relevant, authoritative and timely input for policy development at the EU level and elsewhere. Furthermore, research results can be misinterpreted inappropriately, applied to other sources or exposure conditions or may not adequately address the concerns of stakeholders. In order to properly address the issue of interpretation of scientific results on potential health effects of EMF, this coordination action was launched in 2004 involving 41 participants. The partners includedcoordinatorsofthepreviouslyEUfundedresearchprojects,coordinatorsof researchprojectsatnationallevel(Finland,France,Germany,Greece,Hungary,Italy, UK), representatives of other international activities such as the World Health OrganizationcoordinatedEMFproject,associationsofindustries,manufacturesand trade unions, and regulatory bodies. The main outcome of the project was the production of factsheets on numerous issues related to EMF risks, available on the 1 projectwebsite . Potentialcontributiontothefollowingpolicies: x x x CouncilRecommendationonthelimitationofexposureofthegeneralpublicto electromagneticfields(0Hzto300GHz)(1999/519/EC) Directive 1999/5/EC of the European Parliament and of the Council on radio equipment and telecommunications terminal equipment and the mutual recognitionoftheirconformity Directive 2004/40/EC of the European Parliament and of the Council on the minimumhealthandsafetyrequirementsregardingtheexposureofworkersto therisksarisingfromphysicalagents(electromagneticfields) EUfunding: x 'ScientificSupporttoPolicies'programme 1 http://web.jrc.ec.europa.eu/emfnet 69 Mainresults: x EMFNET has improved the understanding of EMF and health issues, and coordinated research activities. During its time course, it became one of the maininternationalactorsinthisarea; x EMFNETcollatedresearchresultsfromEUfundedprojectsandothernational and international actions, provided a regular update on EMF research (plans, priorities, gaps, prospects from ongoing research, results) and relevant interpretation/adviceforthefacilitationofpolicydevelopmentoptionsbythe EUandotherbodies; x TheEMFNETEuropeanFastResponseTeamonEMFandHealth,answered,on short notice, specific questions of the European Commission services concerningpotentialhealthimpactsofEMF; x EMFNET published more than 40 reports and 20 fact sheets and expert opinions, four EMF and healthrelated publications, and organised and co organised various seminars, workshops and conferences on specific policy relatedEMFandhealthtopics.Theseareavailableontheprojectwebsite; 2 x SomeprojectactivitiesweretakenoverbyaprojectcalledEFHRAN ,fundedby theEuropeanCommission'sHealthandConsumersDirectorateGeneral. Coordinator: x National Research Council, Institute of Biomedical Engineering, Milan, IT (Dr.PaoloRavazzani) Otherbeneficiaries: Organisation Country FraunhoferInstitute,Hannover DE InternationalAgencyforResearchonCancer,Lyon FR EuropeanCommission,JointResearchCentre,Ispra IT FI UniversityofKuopio VerumFoundationforBehaviourandEnvironment,Munich DE NationalAgencyforNewTechnologies,EnergyandtheEnvironment IT ofItaly(ENEA),Rome UniversityofGenoa IT NationalCentreforScientificResearch(CNRS),Villejuif FR CH WorldHealthOrganization,Geneva GraduateSchoolofChemistry,BiologyandPhysicsofBordeaux FR (ENSCBP) TechnicalUniversityofGraz AT FranceTelecom,IssylesMoulineaux FR 2 EFHRANEuropeanhealthriskassessmentnetworkonEMFexposurehttp://efhran.polimi.it 70 ResearchAssociationforRadioApplications,Bonn AristotleUniversity,Thessaloniki 'FredericJoliotCurie'NationalResearchInstituteforRadiobiologyand Radiohygiene,Budapest UniversityofRome'LaSapienza' NationalHealthInstitute(ISS),Rome FoundationforResearchonInformationTechnologiesinSociety, Zürich InternationalCommissiononNonIonizingRadiationProtection, Oberschleissheim UnionoftheElectricityIndustryEurelectric,Brussels EuropeanTelecommunicationNetworkOperators'Association, Brussels UniversityofLeeds GsmAssociation,London InternationalGlobalEthicsAssociationIgea,Ghent RadiationandNuclearSafetyOrganization(STUK),Helsinki MobileManufacturersForum,Brussels UniversityofBologna KarolinskaInstitute,Stockholm/Huddinge FinnishInstituteofOccupationalHealth,Helsinki UniversityofBradford EuropeanTechnicalTradeUnionOfficeforHealthandSafety,Brussels FederationofFrenchElectrical,ElectronicandCommunication Industries(FIEEC),Paris ARCSeibersdorfResearchGmbh,Seibersdorf NationalRadiologicalProtectionBoard,Harwell CentralInstituteforLabourProtection–NationalResearchInstitute, Warsaw NationalInstituteforOccupationalsafetyandPrevention(ISPESL), Rome NationalInstituteforWorkingLife,Stockholm FlemishInstituteforTechnologicalResearch(VITO),Mol 71 DE EL HU IT IT CH DE BE BE UK UK BE FI BE IT SE FI UK BE FR AT UK PL IT SE BE 72 CONTRACTNUMBER:502671 PROJECTTYPE:Coordinationaction TOTALPROJECTCOST:€824,977 ECCONTRIBUTION:€824,977 STARTINGDATE:April1,2004 ENDDATE:October31,2008 DURATION:55months ENVIE COORDINATIONACTIONONINDOORAIR QUALITYANDHEALTHEFFECTS Summary: The aim of the ENVIE project was to increase the understanding of the Europewide public health impacts of indoor air quality by identifying the most widespread and significantindoorcauses fortheseimpactsand byevaluatingtheexistingandoptionalbuilding and housingrelated policies for controlling them. It addressed, in particular, the issue regarding how indoor air quality might contribute to the observed rise in asthmaandrespiratoryallergy,togetherwithotheracuteandchronichealthimpacts. Itbuiltonthebroadscientificexperienceandthewealthofaccumulatedliterature from the domestic and international indoor air research projects as well as the variouscommitteesandexpertgroupsduringthepast20years.Theintentionwasto focusfromthestartonthoseindoorairqualityissuesthathavethehighestEurope wide health relevance. Having defined a shortlist of such 'reverse' indoor health exposuresourcechains,theprojectevaluatedthepolicyalternativesforminimising unwantedhealthconsequences,intermsofachievablepublichealthbenefits,while takingintoaccountpolitical,legal,technological,economicalandsocialfeasibility.A further outcome was the identification of a set of advisable and feasible indoor air quality policy options for Europe. The final results are available on the project 3 website (Fourcomprehensivereports:HealthEffects;IndoorAirPollutionExposure; Characterisation of Spaces and Sources; Policies on Indoor Air Quality: Assessment andNeeds). Potentialcontributiontothefollowingpolicies: x Regulation (EC) no 1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) Directive2001/95/ECongeneralproductsafety Directive89/106/EECrelatingtoconstructionproducts Directive2010/31/EUontheenergyperformanceofbuildings EUclimateandenergypackage x x x x EUfunding: x 'ScientificSupporttoPolicies'programme 3 www.envieiaq.eu/home.html 73 Mainresults: x x x x x Ashortlistof'reverse'indoorhealthexposuresourcechainswasdefined; A set of highly advisable and feasible indoor air quality policy options for Europewasidentified; Likely public health gains, represented by disabilityadjusted life years (DALY) reductions, were calculated, which could be achieved by the selection of differentgeneralandspecificindoorairqualitypolicies; Recommendationswereprovidedon 9 energyefficiency, buildingmaterials,productsandmaintenance,policies concerningtheimpactsofoutdoorenvironment; 9 policiesconcerningspecificbuildingconstructionsandequipment; 9 the development of health based ventilation guidelines to control exposuretopollutantsfromindoorandoutdoorsources,includingindoor moisture,andensurecomfortableindoortemperature; 9 the development of moisture control guidelines for building design and maintenance; AframeworkforaEUGreenPaperonindoorairqualitywasproposed:Thelist of proposed policies clearly shows that to tackle indoor air quality there is a needforanintegrativeapproach. Coordinator: x Institute of Mechanical Engineering, Lisbon, PT (Prof. Eduardo de Oliveira Fernandes) Otherbeneficiaries: Organisation NationalInstituteforHealthandWelfare(THL),Kuopio UniversityofMilan CommissionoftheEuropeanCommunitiesDirectorate GeneralJointResearchCentre,Ispra HelsinkiUniversityofTechnology NorwegianInstituteforAirResearch(NILU),Kjeller JózsefFodorNationalCentreforPublicHealth,Budapest InteruniversityMarineBiologyandAppliedEcologyCentre 'G.Bacci'(CIBM),Livorno TechnicalUniversityofDenmark,KongensLyngby AarhusUniversity,Roskilde SwedishNationalTestingandResearchInstitute,Borås AssociationforResearchandIndustrialCooperationof AndalusiaF.dePaulaRojas"(AICIA),Sevilla BuildingResearchInstitute(ITB),Warsaw CharlesUniversity,Prague RomeEnvironmentalHealthAuthority CranfieldUniversity 74 Country FI IT IT FI NO HU IT DK DK SE ES PL CZ IT UK CONTRACTNUMBER:022618 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€1990185 ECCONTRIBUTION:€1990185 STARTINGDATE:December1,2005 ENDDATE:March31,2009 DURATION:40months EPIBATHE ASSESSMENTOFHUMANHEALTH EFFECTSCAUSEDBYBATHINGWATERS Summary: EPIBATHE investigated the health risks associated with bathing waters to support reviews and revision of the EU’sBathingWaterDirective. It reviewed the international literature and research on all health risks from bathing waters. It defined gaps in current data that restrict the application of ‘evidencebased’ policy to European bathing water standards, and developed research protocols to fill the gaps. It undertook research across two bathing seasons, with the first epidemiological studies in the Mediterranean and Hungary. At the end, it produced a detailed policy interpretation of the findings. 4 Moreinformationcanbefoundonthefollowingwebsite . Potentialcontributiontothefollowingpolicies: x Directive2006/7/ECconcerningthemanagementofbathingwaterquality EUfunding: x 'ScientificSupporttoPolicies'programme 4 http://ec.europa.eu/research/fp6/ssp/epibathe_en.htm 75 Mainresults: x Datawereacquiredfromtheeightepidemiologicalstudiescompleted2006and 2007. This information on EU fresh and Mediterranean waters has been analysed separately and also combined with existing data acquired using the same research methods in Germany and the United Kingdom. This meta analysis of the larger data set includes data on over 7 000 volunteers who participatedintheserandomisedcontrolledtrialsbetween1989and2007; x Water quality encountered during the Hungarian and Spanish investigations wasrelatively‘clean’aswouldbeexpectedfromthechoiceofsites,whichwere incompliancewiththeImperativestandardoftheEUbathingWaterDirective (1976). However, elevations in symptom reporting in the bather group, i.e., when compared to the nonbather group, were observed. It was also notable that the background rates of most symptoms, principally gastrointestinal (GI) symptoms, was lower in the EPIBATHE studies than in previous studies in the UKandGermany.Thesetemporaldifferencescouldbeduetoimprovementsin effluent treatment and the general health status of the European population overthe20yearperiodspannedbytheseinvestigations; x Theanalysisofthecombineddataset,specificallythecomponentfocusedon GIsymptoms,suggeststhatenterococciarebestpredictorofillnessinbathers using marine waters and Escherichia coli is a better index of GI symptoms in bathers using freshwater. The evidencebase created by this analysis suggests thatexposuretomarinerecreationalwaterspresentsapproximatelytwicethe risk associated with fresh waters containing similar faecal indicator organism densities. The EPIBATHE empirical field studies and combined data analysis does not suggest that a change in the water quality standards suggested by eithertheWHOortheEuropeanUnionareinneedofrevision; x The EPIBATHE project has produced data suggesting significant limitations in the microbiological methods defined in the revised Bathing Water Directive (2006); x The EPIBATHE team established relevant links and transmitted information to endusers in the European Commission and WHO, responsible for the developmentofinternationalwaterqualityguidelines. Coordinator: x UniversityofWales,Aberystwyth(Prof.DavidKay) Otherbeneficiaries: Organisation JózsefFodorNationalCentreforPublicHealth,Budapest Rovira&VirgiliUniversity,Reus NationalPublicHealthServiceofWales,Cardiff UniversityofEastAnglia,Norwich WorldHealthOrganisation,Geneva 76 Country HU ES UK UK CH CONTRACTNUMBER:022580 PROJECTTYPE:Coordinationaction TOTALPROJECTCOST:€1055000 ECCONTRIBUTION:€1055000 STARTINGDATE:October1,2005 ENDDATE:September30,2007 DURATION:24months ESBIO DEVELOPMENTOFACOHERENT APPROACHTOHUMAN BIOMONITORINGINEUROPE Summary: A group of 22 European experts on human biomonitoring, coming from national governments, research institutes, industry and nongovernmental organisations in 17 EU member states and Croatia, worked together in the ESBIO coordination action to prepare a coordinatedEuropeanapproachonhumanbiomonitoring.Humanbiomonitoringisa scientific approach for assessing human exposure to and health effects of environmentalpollutantsbasedonsamplingandanalysisofhumantissuesandfluids (e.g.,blood,urine).Itisseenasapotentiallypowerfultooltosupportenvironmental policy as well as public health policy. Human biomonitoring was therefore an importantelementoftheEuropeanEnvironmentandHealthActionPlan20042010. ThefirstpartoftheworkconsistedofthetechnicalpreparationoftheEuropeanpilot projectthatwastobelaunchedduringtheActionPlan(itwaslaunchedin2011).The workofESBIOwasmainlyfocussedonpreparationoftheconceptforacoordinated EUapproach,developmentofqualitycontrolandassuranceprotocols,elaborationof howbiomonitoringresultscanbeintegratedmostefficientlywithenvironmentand registeredhealthdataanddevelopmentofcommunicationstrategiesandscenarios foramoreextensiveuseofhumanbiomonitoringforpolicymaking.Thefinalreport 5 isavailableontheprojectwebsite .Theworkhascontinuedthroughthefollowup 6 7 projects COPHES and DEMOCOPHES , funded by FP7 and LIFE+ programme, respectively. Potentialcontributiontothefollowingpolicies: x EuropeanEnvironmentandHealthStrategy[COM(2003)338] x EuropeanEnvironment&HealthActionPlan20042010"[COM(2004)416] x Regulation (EC) no 1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) EUfunding: x 'ScientificSupporttoPolicies'programme 5 www.euhumanbiomonitoring.org/sub/esbio.htm COPHESEuropeancoordinationactiononhumanbiomonitoringwww.euhbm.info DEMOCOPHESDemonstrationofastudytocoordinateandperformhumanbiomonitoringona Europeanscalehttp://www.euhbm.info/democophes 6 7 77 Mainresults: x An effective network on human biomonitoring on a European level was established and an EUwide harmonised approach for human biomonitoring hasbeenelaborated; x The coordination action has drafted protocols for the following: (i) for a harmonised way of collecting and analysing selected pollutants; (ii) for data management; (iii) for interlaboratory comparison; (iv) for organisation of laboratory work; (v) for population sampling, recruitment and biological sampling; x A conference on the state of the art on human biomonitoring in Europe was held in Lisbon, contributing to the improvement of the communication betweenallstakeholders; x Anelectronichumanbiomonitoringinventorywascreated; x Aconceptwasproposedtoestablishbiomonitoringasapolicymakingtooland guidelinesprovidedforintegrationscenariosandimplementationstrategiesfor biomonitoring; x Knowledgewasgatheredonhowethicalissuesarealreadytakenintoaccount indifferentcountriesandprojects,currentlegalisation; x Themostcosteffectiveandeconomicwaytoperformahumanbiomonitoring pilotprojectwasidentified; x An extensive scientific basis for the utility and sensitivity of biomarkers to be usedinbiomonitoringwasprovided. Coordinator: x BiPROGmbH,Munich,DE(Dr.ReinhardJoas) Otherbeneficiaries: Organisation Country FlemishInstituteforTechnologicalResearch(VITO),Mol BE FederalEnvironmentAgency,Berlin/DessauRosslau DE NoferInstituteofOccupationalMedicine,ód PL LisbonFacultyofMedicine,PreventiveMedicineInstitute PT UniversityofCopenhagen DK CatholicUniversityofLeuven BE FrenchNationalInstituteforHealthSurveillance(INVS),St FR Maurice NL EnvironmentHealthSciencesInternational(EHSI),Hulst StateGeneralLaboratory,Nicosia CY InitiativLiewensufankasbl,Itzig LU EuropeanOilCompanyOrganisationforEnvironment,Healthand BE Safety(CONCAWE),Brussels 78 InstituteforMedicalResearchandOccupationalHealth,Zagreb RegionalEnvironmentalProtectionAgencyforLombardia(ARPA), Milan NationalHellenicResearchFoundation,Athens KarolinskaInstitute,Stockholm/Huddinge RegionalAuthorityofPublicHealth,BanskáBystrica NationalInstituteofPublicHealth,Prague AustrianFederalEnvironmentAgency,Vienna FinnishInstituteofOccupationalHealth,Helsinki HealthProtectionAgency,Salisbury/Didcot/Chilton NationalInstituteforHealthDevelopment,Tallinn HR IT EL SE SK CZ AT FI UK EE 79 80 CONTRACTNUMBER:037019 PROJECTTYPE: Coordinationaction TOTALPROJECTCOST:€3209528 ECCONTRIBUTION:€3209528 STARTINGDATE:November1,2006 ENDDATE:April30,2010 DURATION:42months HENVINET HEALTHANDENVIRONMENTNETWORK Summary: The aim of HENVINET was to support policy making to protect the health of populations and individuals. These policies need to integrate environmental and health issues. The main objective of HENVINET was to establish a longterm co operationbetweenresearchers,policymakersandotherstakeholdersintheareaof environment and health research and assessment. The project reviewed, exploited anddisseminatedknowledgeonenvironmentalhealthissuesbasedonresearchand practices.Thefocusoftheprojectwashumanhealthandthepossibilityofimproving healthaswellasreducingtheapparentincreaseintheprevalenceofcertaindiseases. Thefourprioritydiseasesandeffects,broadlydefinedintheEuropeanEnvironment and Health Action Plan 20042010, were chosen as the starting topics the project focused on: Asthma and allergies; cancer; neurodevelopmental disorders; and endocrine disrupting effects. HENVINET identified over 100 tools used in a number of different decision making contexts: from everyday operation by health practitioners to strategic longterm planning of policies for reducing the negative effects of the environmentonhealth.Suchtoolsincludesoftwaremodels,guidelines,handbooks, orsimpleindicators.Theyareaccessiblethroughasearchablemetadatabaseonthe 8 projectwebsite .Fourpolicybriefswereproduced:onbrominatedflameretardants decabromodiphenyl ether (decaBDE) and hexabromocyclododecane (HBCD); phthalates; impacts of climate change on asthma and other respiratory disorders; andthepesticidechlorpyrifos(CPF). Potentialcontributiontothefollowingpolicies: x EuropeanEnvironmentandHealthStrategy[COM(2003)338] x EuropeanEnvironment&HealthActionPlan20042010"[COM(2004)416] EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 8 http://henvinet.nilu.no 81 Mainresults: x A HENVINET developed a knowledge evaluation method and applied it to examples taken from four groups of health endpoints: asthma and allergies, cancer,neurodevelopmentaldisorders,andendocrinedisruptingeffects; x The evaluation methodology has three main steps: (i) First, based upon scientific review, the consortium translated each of the identified environmental health issues into a schematic framework using a causal chain diagram (DPSEEA framework). A webbased questionnaire was developed to engage experts to assess the diagrams completeness and accuracy, and the stateofknowledgeineachelementandlink;(ii)Inthesecondstep,theresults ofthefirststepweresummarisedandsubmittedforexternalexpertdiscussion withtheaimtoidentifyexpertagreementsanddisagreements,andtoprovide a list of prioritised actions for policymakers; (iii) In the final step, the results weresubmittedtodecisionmakersforfeedbackontheprocessandresults; x Theonlineexpertevaluationwasperformedforthreetypesofcases:(i)apolicy question: the members of the European Respiratory Society were asked how will climate change affect respiratory health; (ii) a risk assessment paradigm evaluated for phthalates, chlorpyrifos, and the brominated flame retardants DecaBDE and HBCD: experts were selected based on the literature review of the last 5 years; and environmental determinants of disease, assessed for specifictypesofcancer:aprofessionalsocietywasconsulted; x Amajorscientificachievementwasarrivedatbythecancertopicgroup,which was able to translate the knowledge about environmental determinants of cancerintoaseriesofsimplecausalchaindiagrams; x As an emerging issue, the consortium has chosen nanoparticles for expert evaluation,inordertoidentifythemostimportantgapsinscientificknowledge of various aspects of the causeeffect relationship between engineered nanoparticles and their potential health risks. The work resulted in a publicly accessibletoolforevaluationonline; x The methods on evaluation of knowledge and interpretation of expert elicitation results using the causeeffect diagram as a basis can be used for other environmental health issues. The results may support informed policy makingtoprotectthehealthofpopulationsandindividuals; x Webbasedsearchablemetadatabasesondecisionsupporttoolsareaccessible throughtheHENVINETnetworkingportal; x The HENVINET online networking portal has been established on http://www.henvinet.eufortheglobalenvironmentandhealthcommunity. 82 Coordinator: x NorwegianInstituteforAirResearch(NILU),Kjeller,NO(Dr.AlenaBartonova) Otherbeneficiaries: Organisation Country NationalVeterinaryInstitute,Oslo NO EcobabyFoundation,Amsterdam NL UnitedBristolHealthcareNHSTrust UK PublicHealthServicesGelderlandMidden,Arnhem NL CentralScienceLaboratory,York UK SlovakMedicalUniversity,Bratislava SK InstituteofFoodBioresources,Bucharest RO NationalAgencyforNewTechnologies,Energyandthe IT Environment(ENEA),Rome IT WorldHealthOrganization(WHO)–EuropeanCentrefor EnvironmentandHealth,Rome UniversityofHertfordshire,Hatfield UK WageningenUniversity NL UniversityofOslo NO InstituteofAppliedScientificResearch(TNO),Utrecht,Zeist NL FinnishMeteorologicalInstitute,Helsinki FI CommissionoftheEuropeanCommunitiesDirectorateGeneral IT JointResearchCentre,Ispra IT ConsortiumforInformationSystems(CSI)Piemonte,Turin InstituteforMedicalResearchandOccupationalHealth,Zagreb HR UmeåUniversity SE NorwegianSchoolofVeterinaryScience,Oslo NO SlovakTechnicalUniversity,Bratislava SK StockholmUniversity SE UniversityofSouthernDenmark,Odense DK NationalCentreforScientificResearchDemokritos,AghiaParaskevi EL AR ArgentineanAssociationofDoctorsfortheEnvironment(AAMMA), BuenosAires BeijingUniversitySchoolofPublicHealth CN IntegralUniversity,Lucknow IN eThekwiniMunicipality,Durban ZA NationalInstituteforPublicHealthofMexico,Cuernavaoa,Morelos MX NationalInstituteforCancerResearch,Genoa IT UniversityofAntwerp BE 83 84 CONTRACTNUMBER:518148 PROJECTTYPE:Coordinationaction TOTALPROJECTCOST:€827720 ECCONTRIBUTION:€800870 STARTINGDATE:March1,2006 ENDDATE:August31,2009 DURATION:42months PHOEBE HARMONISINGPOPULATIONBASED BIOBANKSANDCOHORTSTUDIESTO STRENGTHENTHEFOUNDATIONOF EUROPEANBIOMEDICALSCIENCEIN THEPOSTGENOMEERA Summary: The purpose of PHOEBE was to establish a collaborative research network to identify key issues and to lay the groundwork for efforts to ensure that Europe makes best use of its rich array of populationbased biobanks and longitudinal cohort studies. These include retrospectiveandprospectiveelementstocover majorcohortsthatalreadyexistandneworplannedinitiatives.Particularemphasis wasplacedonstudiesthatcancontributesubstantiallytocoordinatedinvestigations of the genetic and environmental determinants of complex diseases. PHOEBE worked to: (i) Promote communication between major biobanking initiatives; (ii) Enhance the effective sharing and synthesis of information and data; (iii) Avoid expensive mistakes and inefficiencies that can arise when individual initiatives repeatedly'reinventthewheel'.Harmonisationimpliestheuse,wherepossible,of complementary protocols for data management, genotyping, phenotyping, and ethicallegal constructs. PHOEBE cooperated closely with several related, international initiatives including the EUfunded GenomEUtwin (Genomewide analysesofEuropeantwinandpopulationcohortstoidentifygenespredisposingto common diseases), P3G (Public Population Project in Genomics) in Canada and PHGEN (Public Health Genomics European Network). A final conference “HarmonizingBiobankResearch:MaximizingValue–Maximizinguse”wasorganised in Brussels in 2009. The conference gathered more than 250 people from over 35 9 countries. More information is available in the project final report . Some of the 10 11 workhascontinuedintheFP7fundedBBMRI andENRIECO projects. Potentialcontributiontothefollowingpolicies: x Together for Health: A Strategic Approach for the EU 20082013 (COM[2007]630final) EUfunding: x 'LifeSciences,GenomicsandBiotechnologyforHealth'thematicpriority 9 http://www.fhi.no/dav/8cb1c605e3.pdf BBMRIBiobankingandbiomolecularresourcesresearchinfrastructurewww.bbmri.eu ENRIECOEnvironmentalhealthrisksinEuropeanbirthcohortswww.enrieco.org 10 11 85 Mainresults: x Throughthecoordinatedeffortsofmultipleprojects,thescienceofbiobanking maturedsubstantiallyduringthelifetimeoftheproject; x These diverse harmonisation initiatives resulted in the emergence of a new reservoirofknowledge,experience,andexpertisethatiscrucialtosharewith the biobanking community and which paves the way for the next phase of harmonisationobjectives; x PHOEBE was committed to mobilising this information within the biobanking communityforthepurposeofmaximisingthescientificvalue,useandutilityof ourbiomolecularresources; x TohelpinthisendeavourPHOEBEhasbeenactivelyengagedinorleadingkey meetings, conferences, strategy building initiatives, biobanking projects and training; x The project produced reports and recommendations, guidelines and planned international conferences to promote much needed dialogue within the communityandbetweenstakeholders; x PHOEBE played an instrumental role to enhance crosstalk and collaboration betweenthenextwaveofbiobankingprojects. Coordinator: x NorwegianInstituteofPublicHealth,Oslo,NO(Dr.JenniferHarris) Otherbeneficiaries: Organisation UniversityofBristol UniversityofBonn UniversityofTrieste PompeuFabraUniversity,Barcelona KarolinskaInstitute,Stockholm/Huddinge UKBiobank,Stockport NationalInstituteforHealthandWelfare(THL),Helsinki McGillUniversity,Montreal VUUniversity,Amsterdam NationalInstituteofHealthandMedicalResearch(INSERM), Toulouse UniversityofMontreal UniversityofLeicester ErasmusUniversityMedicalCentre,Rotterdam EstonianGenomeProjectFoundation,Tartu CharlesUniversity,Prague NationalandKapodistrianUniversityofAthens ImperialCollegeofScience,TechnologyAndMedicine,London 86 Country UK DE IT ES SE UK FI CA NL FR CA UK NL EE CZ EL UK CONTRACTNUMBER:044159 PROJECTTYPE:Coordinationaction TOTALPROJECTCOST:€750000 ECCONTRIBUTION:€750000 STARTINGDATE:January1,2007 ENDDATE:December31,2009 DURATION:36months PRONET POLLUTIONREDUCTIONOPTIONSNETWORK Summary: There is a lack of systematic exchange of information and experience among EU MemberStatesontheissueofenvironmental healthprotection.Forthispurposeitwouldbe usefultoidentifyandanalysenationalandregionalactivitiesandtoexchangegood practices.ThemainobjectiveofthePRONETprojectwastofacilitateexchangeand evaluationofinterventionsonenvironmentandhealthexposurereductionmeasures on a regional level and promote implementation of successful initiatives in other regions of Europe. This project focused on the exchange of useful practices in two areas: (i) the reduction of transportrelated health hazards (air pollution and noise); and (ii) the improvementoftheindoorenvironment.Astheyare key areas in environmental policy, the health of the population would benefit significantly from exposure reduction measures. PRONET set up an information exchange platform for the development of effective PRONET and efficient health promotionbased policies. It formedanetworkofregionalauthoritiesandresearchersatEuropean,nationaland regionallevel.Theprojectestablishedalinkthroughpartnersandmemberstatesto the Transport, Health and Environment PanEuropean Programme (THE PEP), the EuropeanLocalTransportInformationService(ELTIS)andotherrelevantprojects.At workshops, network members came together to identify, analyse, assess and develop policy options, to gain insight into interventions and to disseminate the results to all stakeholders in European regions to accelerate the progress in environmentalhealthprotection.Theresultsareusedtomakerecommendationsfor 12 policiesatregionallevel.Moreinformationisavailableonthewebsite . Potentialcontributiontothefollowingpolicies: x EuropeanEnvironmentandHealthStrategy[COM(2003)338] x EuropeanEnvironment&HealthActionPlan20042010"[COM(2004)416] x ThematicStrategyontheUrbanEnvironment[COM/2005/0718final] EUfunding: x 'ScientificSupporttoPolicies'programme 12 www.proneteurope.eu 87 Mainresults: x PRONETbuiltaEuropeannetworkofpotentialstakeholderswithinthefieldsof indoorenvironmentandtransport,inordertofacilitateexchangeofexamples ofgoodpractice.ItestablishedcooperationwithotherEuropeanprojects,e.g., THEPEPandtheWHOproject'Actionstoreducehealthrisksduetoindoorair pollutionwithbiologicalagents'; x A database with diverse, innovative case studies was built: diverse in a spatial/geographicalsenseandcoveringavarietyoftopics,suchasreductionof volatileorganiccompoundsfrombuildingmaterials,reductionofallergens,or improvement in ventilation behaviour with respect to indoor environment. In thefieldoftransportthetopicsrangedfromalternativefuels,trafficzoningand congestionchargingtocomprehensivemethodsofpollutionreduction; x Most of the examples of good practices were collected by contacting a large number of stakeholders. For indoor environment, this resulted in a total of about150entriesandfortransportinabout400entries; x As regards indoor environment, case studies were grouped in 9 main categories: ventilation, radon, noise, moisture, moulds, allergens, volatile organic compounds, environmental tobacco smoke and combustion. As for transport, case studies were categorised in 10 groups: traffic restrictions, low emission vehicles, traffic or spatial planning, promotion of cycling, logistic concepts, awareness raising, public transport, comprehensive approaches, administrative/politicalinstruments,andnetworksanddatabases; x An assessment form was developed, aimed at reviewing the effectiveness of thecollectedcasestudies; x Factsheetswerecreatedfortheindoorandtransportcasestudies(availableon the project website). Keywords are available in each of the 23 official EU languages; x Forindoorenvironment,thefactsheetsconsistofthefollowinginformation:(i) The title, category and whether it is applicable in schools, homes or other settings;(ii)Adescriptionoftheproblem;(iii)Anoverviewofthemeasureand theactionsthatshouldbetaken;(iv)Adescriptionofthecasestudyonwhichit was based, including contact information of the case owner; (v) Some additional points in relation to the applicability that should be taken into account; x For transport, the information that is included in the fact sheet is slightly different from that in the indoor environment sheet: (i) The title and the categoryofthemeasure;(ii)Somegeneralinformationonwhathasbeendone within the measure; (iii) The expected or achieved results (reduction in exposureand/orimprovementinhealth);(iv)Someadditionalpointsinrelation to the applicability, that should be taken into account; (v) Conditions/restrictions that might be relevant; (vi) Contact information of the caseowner. x Results were disseminated to, e.g., ministries by, among others, the organisationoflocalworkshops. 88 Coordinator: x Public Health Services Gelderland Midden, Arnhem, NL (Dr. Peter van den Hazel) Otherbeneficiaries: Organisation Country MinistryoftheEnvironmentandConservation,Agricultureand DE ConsumerProtectionoftheStateofNorthRhineWestphalia, Düsseldorf MinistryforHousing,SpatialPlanningandEnvironment,DenHaag NL StockholmCountyCouncil SE NationalInstituteforPublicHealthandtheEnvironment(RIVM), NL Bilthoven NationalEnvironmentalResearchInstitute,Roskilde DK AT MedicalUniversityofVienna PublicHealthAgencyofBarcelona ES 89 90 CONTRACTNUMBER:513648 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€2847858 ECCONTRIBUTION:€2247624 STARTINGDATE:January1,2005 ENDDATE:March31,2007 DURATION:27months VIROBATHE METHODSFORTHEDETECTIONOF ADENOVIRUSESANDNOROVIRUSESIN EUROPEANBATHINGWATERSWITH REFERENCETOTHEREVISIONOFTHE BATHINGWATERDIRECTIVE76/160/EEC Summary: 13 Themainaimoftheproject wastoprovideaprocedure for analysis of EU bathing waters for noroviruses and adenoviruses by validated comparisons of methods for processing water samples to achieve the best virus recovery consistent with cost and feasibility of use in routine monitoring laboratories. The specific objectives wereto:(i)comparemethodsfornorovirusandadenovirus detection in recreational waters; (ii) derive a combination of concentration and detection techniques to provide a reproducible system of testing bathing waters for the target viruses; (iii) furnish scientific evidence to provide support for norovirus and adenovirus testing of environmental samples in respectoftheirroleastheappropriateviralindicatoroffaecalpollution;(iv)prepare the technology for EU Accession States as part of the development of their environmentalandsocialprogrammes;(v)sharetechnologybetweenlaboratoriesto achievewidercompetenceinthevirologicalanalysisofenvironmentalmaterials.The resultsfromVIROBATHEprovideabasisforfurtherworktolinkvirusoccurrencewith healtheffectsofrecreationalwateruse,eitherthroughcorrelationwithenterococci or by epidemiological studies based on projects such as EPIBATHE (described elsewhereinthiscatalogue).VIROBATHEhasshownthattheideaofusingvirusesas anindicatorofpollutionandasavalidparameterintheBathingWaterDirectivehas movedfromthe"conceptual"atthebeginningoftheprojectthroughthe"possible" stagereachedattheendofPhase1,wherethemethodswereshowntoworkinthe laboratory, to the "feasible" stage, where structured field studies have furnished evidencethatvirusescanbedetectedinsurveillanceprogrammes. Potentialcontributiontothefollowingpolicies: x Directive2006/7/ECconcerningthemanagementofbathingwaterquality EUfunding: x 'ScientificSupporttoPolicies'programme 13 www.virobathe.org 91 Mainresults: x TheprojectconcludedthatitisfeasibletointroducetheVIROBATHEdeveloped virusconcentrationanddetectionmethodsintovirologylaboratoriesofawide rangeofskillsandexpertise; x Target viruses could be concentrated by relatively inexpensive techniques, which should therefore be adaptable to routine environmental monitoring laboratoriesandtolaboratoriesincountrieswithlowresourceprovision; x Thechosenconcentrationmethodwasapplicableacrossallthefreshwaters– fromFrancetoPoland; x Adenoviruses and noroviruses were present in fresh and marine recreational watersandweredetectablewithvaryingfrequency; x TargetviruseswerewidelypresentinenvironmentalsamplesacrossEurope; x Adenoviruses were found to be statistically associated with human faecal pollutioninfreshwater; x Methodological considerations: (i) The nested polymerase chain reaction (nPCR) for adenovirus is reliable; (ii) at least some of the samples contained infectious adenovirus as detected by the integrated cell culture polymerase chain reaction (ICCPCR) method; (iii) detection, especially for adenoviruses, canbequantifiedbyaquantitativePCRtechnique;(iv)Noroviruseswerefound not to be a practical target for surveillance as they were not sufficiently abundantnorwasthereversetranscriptase(RT)PCRrobust;(v)Moreworkis needed to optimise a method for marine waters; (vi) Further work on nucleic acidextractionisneededtooptimiserecoveryaswellasonreducinginhibition ofthePCRbycomponents,especiallyinfreshwater; x The next stage will be to move from "feasible" to "operational", where quantitative determinations of target viruses (probably adenoviruses) will be reconciledwithlevelsofknownfaecalindicators(probablyenterococci)sothat meaningfuldiscussionsontheformulationofaviralparameterbasedonsound scientificdatacanbeheld. 92 Coordinator: x UniversityofWales,Aberystwyth,UK(Prof.DavidKay) Otherbeneficiaries: Organisation UniversityofPisa CentralScienceLaboratory,York NationalInstituteforPublicHealthandtheEnvironment (RIVM),Bilthoven UniversityofRome"TorVergata" PublicHealthServiceofBadenWürttemberg,Stuttgart HenriPoincaréUniversity,Nancy EnvironmentAgency,Starcross UniversityofBarcelona BavarianHealthandFoodSafetyAgency,Oberschleissheim FederalEnvironmentAgency,Berlin NationalVeterinaryInstitute,Oslo NationalHealthInstitute(ISS),Rome UniversityofPortoFacultyofPharmacy StateGeneralLaboratory,Nicosia HealthProtectionAgency,Reading 93 Country IT UK NL IT DE FR UK ES DE DE NO IT PT CY UK 94 CHAPTERIIProjectsFocusedontheEffectsofExposuretoEnvironmentalStressorsandUnderlyingMechanisms CHAPTERII Projectsfocusedontheeffectsof exposuretoenvironmental stressorsandunderlying mechanisms 95 96 CONTRACTNUMBER:22923 PROJECTTYPE:Specifictargeted researchproject TOTALPROJECTCOST:€4925004 ECCONTRIBUTION:€4610000 STARTINGDATE:April1,2006 ENDDATE:31March,2010 DURATION:48months ATHON ASSESSINGTHETOXICITYANDHAZARDOF NONDIOXINLIKEPCBSPRESENTINFOOD Summary: Polychlorinated biphenyls (PCBs), previously used onalargescaleforindustrialpurposes,areagroup oftoxicfoodcontaminantsthatareveryresistantto degradation.Althoughnowprohibited,duetotheir persistencePCBsarestillabundantintheenvironmentandpresentinhighlevelsin foods such as meat, fish and dairy products. Nondioxinlike PCBs (NDLPCBs) are poorly characterised from a toxicological point of view. ATHON was initiated to increasetheknowledgeonhealthhazardsofNDLPCBsinfood.Usingexperimental models,textminingandmathematicalmodelling,effectsafterexposuretoNDLPCBs were investigated in a controlled and reproducible manner. The results show that PCBs can be transferred rapidly across the placental barrier by passive diffusion. Neurotoxicity studies within ATHON increased the knowledge on underlying mechanisms that may contribute towards the epidemiology reports of cognitive impairment in children exposed to PCBs during pregnancy and lactation. Gene expressionchangesafterexposuretoseveralPCBswereobservedindifferentbrain areas. Both transcriptomics and proteomics revealed a genderspecific reaction to thePCBexposure.Bodyand organ relatedtoxicityendpointswerealsochangedas wellasendpointsrelatedtodevelopmentandreproduction.Afinalprojectsummary 1 isavailableontheprojectwebsite . Potentialcontributiontothefollowingpolicies: x x x x Council Regulation (EEC)315/93 laying down Community procedures for contaminantsinfood;CommissionRegulation(EC)1881/2006settingmaximum levels for certain contaminants in foodstuffs; Commission Regulation (EC)1883/2006 laying down methods of sampling and analysis for the official control of levels of dioxins and dioxinlike PCBs in certain foodstuffs; Commission Recommendation 2006/88/EC concerning the reduction of the presence of dioxins, furans and PCBs in feedingstuffs and foodstuffs; Commission Recommendation 2006/794/EC on the monitoring of background levelsofdioxins,dioxinlikePCBsandnondioxinlikePCBsinfoodstuffs CommunityStrategyforDioxins,FuransandPolychlorinatedBiphenyls Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Foodqualityandsafety'thematicpriority 1 www.cascadenet.org/~athon 97 Mainresults: x x x x x x x Studies after developmental and adult exposure in vivo (rats and mice) collectively indicated that one of the characteristic effects of NDLPCBs is disruptionofthyroidhormonehomeostasis.Forthehumansituation,however, itisnotclearwhetherPCBexposureleadstosimilareffects; AvarietyofcytochromeP450relatedchangeswereobservedinliver; Evaluation of the in vivo and in vitro neurotoxicity studies within ATHON increased the knowledge on underlying mechanisms that may contribute towardstheepidemiologyreportsofcognitiveimpairmentandmotordisorders in children exposed to PCBs during pregnancy and lactation. The effects observedalsoincludedisturbedauditoryfunctionandafeminisedbehaviourin males; Gene expression changes after exposure to several PCBs were observed in different brain areas as well as in peripheral blood. Both transcriptomics and proteomicsrevealedagenderspecificreactiontothePCBexposure; Evaluationperformedonbodyandorganrelatedtoxicityendpointsaswellas endpointsrelatedtodevelopmentandreproductionrevealedslightlyincreased neonatal mortality, slight delays in developmental milestones, transient decreased body weight, increased liver weight and changes in bone mineral density; Exposure to NDLPCBs was shown to have tumourpromoting activities on proteinlevelbothinvivoandinvitro; SeveralarticlesrelatedtothequalitativeandquantitativetoxicitydataforNDL PCBsgeneratedwithintheprojecthavebeenpublishedandfurtherarticlesare planned. Coordinator: x KarolinskaInstitute,Stockholm,SE(Prof.HelenHåkansson) Otherbeneficiaries: Organisation FlemishInstituteforTechnologicalResearch(VITO),Mol VeterinaryResearchInstitute,Brno PrinceFelipeResearchCentre,Valencia NationalInstituteforHealthandWelfare(THL),Kuopio TechnicalUniversityofKaiserslautern InstituteofPharmacologicalResearchMarioNegri,Milan UtrechtUniversity,InstituteforRiskAssessmentSciences VUUniversity,Amsterdam UniversityofOslo UmeåUniversity UnitedBristolHealthcareNHSTrust HealthCanada,Ottawa GermanStatutoryAccidentInsurance,Bochum 98 Country BE CZ ES FI DE IT NL NL NO SE UK DE CONTRACTNUMBER:506319 PROJECTTYPE:Networkofexcellence TOTALPROJECTCOST:€14400000 ECCONTRIBUTION:€14400000 STARTINGDATE:February1,2004 ENDDATE:January31,2010 DURATION:72months CASCADE CHEMICALSASCONTAMINANTSINTHE FOODCHAIN:ANoEFORRESEARCH, RISKASSESSMENTANDEDUCATION Summary: The main objective of the CASCADE Network of Excellence (NoE) was to act as an integrated research networkinthefieldofchemicalcontaminantsinfood.It was originally composed of 19 partner universities and institutes, but has been additionally expanded through the introduction of new partners. CASCADE is today a highly multidisciplinary network. The focus of CASCADE scientific activities was to characterise the health implications of exposure to chemicals acting through nuclear receptors. It focused on a limited set of model chemicals, namely dioxin (TCDD),bisphenolA(BPA),vinclozolinandgenistein.Reliablehealthriskassessment information (e.g., toxicities, mechanisms of actions, human exposure levels, data gaps, research needs) has been provided on TCDD, BPA and vinclozolin. From the startCASCADEdevelopedanextensivetraininganddisseminationscheme.Aftersix years, CASCADE NoE become CASCADE ACERT, a nonprofit association, which will continue to offer training, risk assessment and collaborative partnership as the leadingEuropeannetworkwithinendocrineresearch.Aninternationalpostdoctoral programme(CASCADEFELLOWS)tocontinuetheresearchandresearcherexchange activities of CASCADE has been established. For more information, see the project 2 website . Potentialcontributiontothefollowingpolicies: x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x EuropeanEnvironmentandHealthStrategy[COM(2003)338] x CommunityStrategyforEndocrineDisruptersCOM(1999)706final x Council Regulation (EEC)315/93 laying down Community procedures for contaminantsinfood;CommissionRegulation(EC)1881/2006settingmaximum levelsforcertaincontaminantsinfoodstuffs EUfunding: x 'Foodqualityandsafety'thematicpriority 2 www.cascadenet.org 99 Mainresults: Integrationandtraining x CASCADE has played a significant role in integrating research activities in the field of chemical contaminants in food. It involved not only the research communitybutalsoadditionalstakeholdersandthegeneralpublic; x CASCADE partners exchanged 250 researchers throughout the lifetime of the project,andtheseexchangesarestillongoing; x CASCADEinitiatedcourseprogrammesinclude'Advancedinternationaltraining courses in health risk assessment', 'RACOURSES', 'TRISK' (programme for training/certification of European risk assessors), 'MSTnet' (CASCADE Science RiskAssessmentExpertiseInventoryandtheMathematicalandStatisticalTool); x More than 1 300 PhD and post doctoral students, senior scientists as well as professionals from industry and regulatory authorities attended the 34 differenttrainingcourses,summerschoolsandworkshopsorganised; x CASCADE will continue working towards better integration in the future, for instance with the establishment of the global postdoctoral programme on endocrinedisrupterresearchwithinthecontextofCASCADEACERT; x CASCADEisactivelyengagedindevelopingaEuropeanstructurefortrainingof accredited European risk assessors. CASCADE universities are dedicated to developing joint education for Master’s level and PhD students and promote exchangeofstudentsandteachersbetweentheuniversities; x ScientificintegrationwasachievedbytheinvolvementofCASCADEpartnersin differentscientificcollaborationswithinCASCADEandalsowithotherprojects and international research actors such as the US Environmental Protection Agency(EPA). Scientificactivities x CASCADE has identified listings or databases containing information on established or potential endocrine disrupters that have been produced by governmental, nongovernmental or industrial bodies. Efforts were made to verify the information derived from these sources using publications records. Allthisinformationhasbeencollectedandtransferredtoaconsolidatedlistby eliminating redundancy. In this way a combined dataset with 169 compounds wasobtained,includingnaturallyoccurringproducts,environmentalpollutants, industrialchemicals,agrochemicalsandpharmaceuticalcompounds,withdata abouttheirrelativebindingaffinityforoestrogenreceptors; x CASCADE advanced the state of the science by, among others, (i) the developmentofanalyticalmethodstodetectcertainchemicalcontaminantsin differentfoodmatrixes;(ii)therefinementofinsilicomethodstoassesbinding ofxenoestrogenstooestrogenreceptorD(iii)theintegrationandvalidationof novel analytical and in silico approaches with biological methods; (iv) the generation of novel reporter cell lines to characterise the effects of chemical contaminantsonER,LXR,AhR,AR,TRnuclearreceptorsignallingpathways;(v) the study of the crosstalk between different cellular signalling pathways 100 modulatedbychemicalcontaminants;(vi)thestudyoftheimpactofcellular metabolism on the biological response of chemical contaminants; (vii) the developmentofnovelsmallmodelorganisms(frogsandzebrafish)tostudythe effectsofchemicalcontaminantsinvivo;(viii)theidentificationofintermediate metabolismandmetabolicsyndromerelatedendpointsaspotentialtargetsfor chemical contaminants in food; (ix) the integration of the methodology developed by CASCADE to study the effects of contaminants in whole food (BabyfoodandBread). Dissemination x CASCADE partners have actively participated in the public debate regarding chemicalcontaminantsinfood.CASCADEpartnersandnetworkrepresentatives havebeencontactedbyauthorities,industry,nongovernmentalorganisations (NGOs) and individual European consumers to provide advice and support in theareaofchemicalcontaminantsandtheireffectsonhealth; x The CASCADE project dissemination strategy received in 2011 the 'Communication Stars' award due to its multifaceted communication actions that influenced the EU chemical regulation "REACH". Via campaigns, position papersandopinionpapers,CASCADEhastriedtoinfluencethedecisionmakers in several urgent and important questions. At the time for voting on REACH regulation, CASCADE published an article about REACH implementation in Financial Times. The World Wildlife Fund (WWF) and CASCADE jointly carried outaDETOXcampaign,testing27differentfoodstuffsaroundEurope; x Since2005,CASCADEhaschairedCommNet,whichconsistedofmorethan20 projects.Ithasenhancedthecommunicationqualityinalltheinvolvedprojects fundedbytheEUResearchFrameworkProgramme; x CASCADE has spread visibility via YouTube, Wikipedia YouTube, Wikipedia, Facebook, Cordis, AlphaGalileo, EurActive, EC DG Research, Research*eu and viaatleast20otherwebsites; x The project produced more than 200 scientific publications in peerreviewed journals,151manuscripts,182abstractsfororalpresentationsatmeetingsand 351 abstracts for poster presentations at meetings, 46 theses, 21 reports, 25 bookchaptersandhundredsofposters; x CASCADE has established spinoff companies for management, administration anddissemination. 101 Coordinator: x KarolinskaInstitute,Stockholm,SE(Prof.JanÅkeGustafsson) Otherbeneficiaries: Organisation UniversityofMilan JohannesGutenbergUniversity,Mainz EcoleNormaleSupérieure(ENS),Lyon UniversityofGranada NationalCentreforScientificResearch(CNRS),Paris UniversityofTurku GeorgAugustUniversity,Göttingen UniversityofPécs HelmholtzResearchCentreforEnvironmentalHealth,Munich InstituteofPharmacologicalResearchMarioNegri,Milan NationalInstituteforAgriculturalResearch(INRA),Toulouse EberhardKarlsUniversity,Tübingen KaroBioAB,Huddinge UniversityofHelsinki NationalResearchInstituteforFoodandNutrition(INRAN), Rome NationalInstituteofHealthandMedicalResearch(INSERM), Montpellier SlovakAcademyofSciences,InstituteofExperimental Endocrinology,Bratislava NationalHealthInstitute(ISS),Rome 102 Country IT DE FR ES FR FI DE HU DE IT FR DE SE FI IT FR SK IT CONTRACTNUMBER:506143 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€2591940 ECCONTRIBUTION:€2399940 STARTINGDATE:December1,2003 ENDDATE:December31,2006 DURATION:36months DEVNERTOX TOXICTHREATSTOTHEDEVELOPING NERVOUSSYSTEM:INVIVOANDINVITRO STUDIESONTHEEFFECTSOFMIXTUREOF NEUROTOXICSUBSTANCESPOTENTIALLY CONTAMINATINGFOOD Summary: DEVNERTOXfocusedongeneratingexperimentalmodelstoimprove developmental neurotoxicity testing and risk assessment for neurotoxic food contaminants. There is still limited knowledge about the exact mechanism(s) of action of most environmental neurotoxicants,andthisisoneofthereasonswhytheidentification of endpoints for neurotoxic effects has been progressing slowly. Three compounds were studied alone and in combination: methylmercury (MeHg) andtwopolychlorinatedbiphenyls(PCBs)withdifferentchemicalproperties(PCB153 andPCB126).Themajorgoalswereto:(i)Developtestingprotocolsbasedontheuse of several in vitro experimental models; (ii) Identify biochemical, molecular and functional endpoints based on the mechanism of action of MeHg and PCBs; (iii) Evaluate the neurotoxic effects of MeHg and PCBs during development, including longterm consequences and genderrelated aspects; (iv) Define quantitative measuresofobservedeffectsforriskassessmentpurposes,andtoderiveguidelines forexposurelimits.Theresultsindicatethatthecombineduseofinvitroandinvivo methodologies is a successful strategy to identify neurodevelopmental toxicity and characterise the mechanisms of actions of potentially neurotoxic substances. The analysis of behaviour is a first choice approach to detect subtle and longlasting modificationsinvivo.Learningandmemoryfunctionswereimpairedinbothratsand 3 mice.Adetailedfinalreportisavailableontheprojectwebsite . Potentialcontributiontothefollowingpolicies: x x Council Regulation (EEC)315/93 laying down Community procedures for contaminantsinfood;CommissionRegulation(EC)1881/2006settingmaximum levels for certain contaminants in foodstuffs; Commission Regulation (EC)1883/2006 laying down methods of sampling and analysis for the official control of levels of dioxins and dioxinlike PCBs in certain foodstuffs; Commission Recommendation 2006/88/EC concerning the reduction of the presence of dioxins, furans and PCBs in feedingstuffs and foodstuffs; Commission Recommendation 2006/794/EC on the monitoring of background levelsofdioxins,dioxinlikePCBsandnondioxinlikePCBsinfoodstuffs Regulation (EC) no 1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) EUfunding: x 'Foodqualityandsafety'thematicpriority 3 www.imm.ki.se/devnertox 103 Mainresults: x Thecombineduseofinvitroandinvivomethodologiesisasuccessfulstrategy to identify neurodevelopmental toxicity and characterise the mechanisms of actionsofsubstancesthatarepotentiallyneurotoxic; x Changes were detected in selected mechanismbased endpoints (i.e., neurotransmitters) at concentrations relevant for human developmental exposure; x Neuralstemcellsseemtobeapromisingmodeltoinvestigatedevelopmental neurotoxicity: They are highly sensitive to toxicantsand undergo apoptotic or necroticcelldeathtriggeredbymultipledeathpathwaysthatmaycrosstalk; x Theanalysisofbehaviourisafirstchoiceapproachtodetectsubtleandlong lastingmodificationsinvivo,alsobecauseitoffersthepossibilitytoanalysethe sameanimalsatdifferentstagesofdevelopment; x Learning and memory functions were impaired in both rats and mice. DevelopmentalexposuretoMeHgaffectsnotonlycognitivefunctionsbutalso motivationdrivenbehaviourinmalebutnotfemalemice; x Itisimportanttomeasureactuallevelsintissuesandcellsinordertoenablea comparisonofinvivoandinvitroresults. Coordinator: x KarolinskaInstitute,Stockholm/Huddinge,SE(Prof.SandraCeccatelli) Otherbeneficiaries: Organisation Country UniversityofPavia IT UniversityofParma IT PrinceFelipeResearchCentre,Valencia ES CatholicUniversityofLouvain,Brussels BE UppsalaUniversity SE NoferInstituteofOccupationalMedicine,ód PL TrinityCollege,Dublin IE 104 CONTRACTNUMBER:505609 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€1852095 ECCONTRIBUTION:€1461947 STARTINGDATE:February1,2004 ENDDATE:September30,2007 DURATION:44months DIEPHY DIETARYEXPOSURESTOPOLYCYCLIC AROMATICHYDROCARBONSANDDNA DAMAGE Summary: Exposure from polycyclic aromatic hydrocarbons (PAHs) from some foods is sufficiently high to permit direct studies of DNA lesions in humans. This potential health hazard its modulation by genetic factors, synergists and protective substances 4 constituted the main focus for DIEPHY . New methods for assessing oxidative and other types of DNA damage as well as basic knowledge on different DNA repair mechanisms were also provided. The impact from exposures via food to PAHs was studied in women characterised by different ethnicity and life stylesfromthegeneralpopulationinPoland,SerbiaandItaly,as wellasinsubjectslivingintwoenvironmentalcatastrophezonesinSerbia.Thestudy oftheeffectsofcombinedexposurestoPAHsandhighlevelsofarsenicindrinking water was unique, as was the assessment of individual DNA repair capacity, which offersapossibilitytoidentifyparticularlysensitivegroupswithrespecttothistypeof carcinogen.Inhumanstheutilityofvariousbiomarkersderivedfrommodelsystems, relevant for tumour induction by PAHs, was directly assessed by monitoring chromosomal and DNA damage in buccal cells and lymphocytes. The inhibiting effects of anticarcinogens with respect to DNA damage and chromosomal aberrations induced by exposure to PAHs was assessed directly in isolated lymphocytes and buccal cells from human volunteers in an intervention crossover study.Intheareaofpublichealth,effortsweremadetopromoteahealthierdietfor thegeneralpopulation. Potentialcontributiontothefollowingpolicies: x Commission Regulation (EC) No 627/2006 implementing Regulation (EC) No 2065/2003 of the European Parliament and of the Council as regards quality criteria for validated analytical methods for sampling, identification and characterisationofprimarysmokeproducts x CommissionRegulation(EC)No1881/2006settingmaximumlevelsforcertain contaminantsinfoodstuffs EUfunding: x 'Foodqualityandsafety'thematicpriority 4 http://medpr.imp.lodz.pl/diephy/home.htm 105 Mainresults: x Diolepoxides derived from benzo(a)pyrene (BPDE), dibenzo(a)pyrene (DBPDE), fluoranthene(FADE)andbenzophenanthrene(B(c)PhDE)wereinvestigatedin terms of mutagenic efficacy, replication bypass by recombination and trans lesionDNAsynthesis,incisionratesandrepairkinetics.Ofthethreecompounds tested, DBPDE was the most toxic, mutagenic, and recombinogenic, whereas FADEistheleast reactiveandgave fewermutations per recombinationevent ascomparedtoBPDE.TheDBPDEadductsappearedtobemoremutagenicand recombinogenicthantheBPDEadducts.Theresultssuggestanimportantrole ofnucleotideexcisionrepairforcellularresistancetoDBPDEaffectingboththe inductionofchromosomalaberrationsandsisterchromatinexchanges; x Neither chlorophyllin nor ellagic acid exhibited any protective action with respecttotheinductionofDNAadductsinmouseliver; x Cohortsof100nonsmokingwomenfromLodz(PL),Viterbo(IT)andBelgrade (RS)weregenotyped,interviewedwithrespecttolifestylerelatedfactors,and sampled for determination PAHmetabolite patterns, DNA adducts and oxidative damages, and biomarkers for vegetable intake. In addition to the Belgradecohort,100residentsinVojlovicalivingclosetothebombedPanevo refineryandpetrochemicalcomplexeswerescoredwithrespecttomicronuclei (MN)inperipherallymphocytes; x TheconcentrationsofmainPAHurinarymetabolitesfoundintheItaliancohort compared closely to findings in Germany, indicating similar PAH levels in ambientairandconsumedfood.ElevatedconcentrationsofPAHmetabolitesin the Polish and Serbian cohorts reflect significantly higher exposures from ambientairand/orcontaminatedfood; x TheanalysisoftheMNdataforwomenlivinginBelgradeshowedasignificantly lower frequency for the subgroup consuming vitamin supplements versus individualswhodidnot; x Vegetableanalysisshowedthattheworkersandthepeoplelivinginthevicinity ofthePanevorefineryarenotsubjecttoanincreaseofambientPAHexposure causallylinkedtotheproductionofthepetrochemicalcomplexoftherefinery; x Analysis of genetic polymorphisms in major metabolising and DNA nucleotide excision as well as base excision repair genes did not indicate any significant differencesbetweenthethreecohortsinPoland,ItalyandSerbia; x A statistically significant relationship was found between the frequency of having fried, smoked or grilled meat dishes as well as vegetable servings and theDNAfragmentationbyCometassayinPolish,ItalianandSerbianwomen; x TherewasamarkedincreaseofMNfrequencywithageinSerbianwomen,and a statistically significant association between high intake of vitamin supplementsanddecreasedfrequencyofMN; x Relying on data obtained in this project, as well as supported by updated medical information, health advisories intended for the general public have beenpreparedandprintedinthePolishandSerbianlanguages. 106 Coordinator: x NoferInstituteofOccupationalMedicine,ód,PL(Prof.RobertNilsson) Otherbeneficiaries: Organisation Country StockholmUniversity SE KarolinskaInstitute,Stockholm SE InstituteofExperimentalMedicine,Prague CZ UniversityofTuscia,Viterbo IT VincaInstituteofNuclearSciences,Belgrade RS BiochemicalInstituteforEnvironmentalCarcinogens,Prof.Dr. DE GernotGrimmerFoundation,Grosshansdorf 107 108 CONTRACTNUMBER:513943 PROJECTTYPE:NetworkofExcellence TOTALPROJECTCOST:€11000000 ECCONTRIBUTION:€11000000 STARTINGDATE:May1,2005 ENDDATE:October31,2010 DURATION:66months ECNIS ENVIRONMENTALCANCERRISK, NUTRITIONANDINDIVIDUAL SUSCEPTIBILITY Summary: ECNIS brought together European research groups from 25institutionsof13countriesintoanetworktoconduct cuttingedge research on cancer causation and prevention. The participating groups are active in the area of environmental cancer and its modulation by nutrition and genetic makeup. The vision of ECNIS was the creation of a dynamic research network, which aims to decrease cancer incidence by: (i) identifying chemicals or other factors in the environment and food, which cause cancer; (ii) elucidating the mechanisms by which dietary and lifestyle patterns increase or decrease cancer risk; (iii) facilitating the development of new foods with cancer preventive properties; (iv) discovering genetic (hereditary) factors which make individuals more or less susceptible to cancer; and (v) formulating improved approaches to the risk assessment of carcinogens. To reach its objectives, ECNIS activitieswereorganisedaroundthreeaxes:(i)Integratingactivities,topromotethe establishmentofadurablenetworkofEuropeanresearchgroupscommittedtoco ordinated research planning, personnel mobility and sharing infrastructures and data; (ii) Joint research activities, focussed on high quality, multidisciplinary investigations in the area of molecular cancer epidemiology, environmental carcinogenesis and its modulation by nutrition and genetics; and (iii) 'Spreading of excellence'activities,includingresearchertrainingandmobilityprogrammesaswell assharingofnewscientificknowledgewithdifferentstakeholders(researchers,the general public, regulators, health care specialists, industry, etc.). At the end of the 5 project,theprojectwebsite hadbeenvisitedbyover600000people.Thenetwork organised9conferences,75workshopsand13trainingcourseswithalargenumber of attendees. 75 PhD students were trained and 236 joint publications published. ECNISresearchersperformedindepthevaluationsofthestateofsciencerelevantto canceraetiologyandhaveformulatedcorrespondingproposalsforfutureresearch. Potentialcontributiontothefollowingpolicies: x x x Council Regulation (EEC)315/93 laying down Community procedures for contaminantsinfood;CommissionRegulation(EC)1881/2006settingmaximum levelsforcertaincontaminantsinfoodstuffs Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Foodqualityandsafety'thematicpriority 5 www.ecnis.org 109 Mainresults: x AsaresultofcommoneffortoftheECNISresearchers,anumberofinitiatives important for European integrative research on cancer, biomarkers, and food havebeeninitiated: 9 MolecularEpidemiologyandCancer(MEC)database:bringstogetherthe data of a number of population studies, thus providing increased statistical power to evaluate the influence of various environmental or other factors on cancer risk. Currently MEC incorporates information on exposure,includingnutritionandcancerchemoprevention,biomarkersof exposure, biomarkers of individual susceptibility, cytogenetic and other genotoxicdamage,anddatasetsofmolecularepidemiologystudies; 9 Core facilities: provide standardised chemicals, antibodies and analytical methodologyforECNISpartners; 9 EuropeanStandardsCommitteeonUrinaryDNALesionAnalysis(ESCULA): presently comprises 31 laboratories from 16 countries globally. This network focuses on validation of the methods for determination of urinary 8oxo7,8dihydro2’deoxyguanosine (8oxodG), a well establishedbiomarkerofoxidativestress; 9 European Comet Assay Validation Group (ECVAG): comprises 12 laboratoriesfrom9differentEUcountries.Themainobjectiveistoreach consensus on the likely level of DNA damage in lymphocytes and on proceduresandvaluesoftheDNA repairincisionassay,andadditionally development of bona fide internal standard materials to minimise variabilityinthemeasuresofcometassayendpoints; 9 ECNISRepository:hasbeendevelopedintheformofelectronicplatform for storing and providing access to digital documents dealing with the mattersofenvironmentalhazardsforcancer; 9 ECNISvideoconferencingnetwork:isthelargestnetworkofthiskindbuilt inEurope.Itconsistsof23partnergridsallowingpointtopointaswellas multipointsconnections; 9 Training instruments: In additional to more conventional training initiatives,awebbasedcoursetitled‘Molecularepidemiology:principles andapplications’hasbeendeveloped. x ECNISprovidedthegluetobringtogethermanyofthetopEuropeaninstitutes withahighdegreeofspecialisationinindividualrelevantareas,andbeganthe process of developing strategies for the combined use of disciplines of analytical and synthetic chemistry, molecular biology, food science, epidemiology,riskassessmentandethics,withtheultimateintentionofmaking them available for panEuropean cancer molecular epidemiology studies, i.e., studiesofpopulationsfromdifferentregionsofEuropewithdifferentclimates, pollutionlevelsanddietaryhabits; x The ECNIS Network of Excellence was only the first stage of the process of creating a strongly integrated and viable European research network. Having drawn together the most relevant parties towards this task and also having 110 identifiedthemajorgapsinavailabledataandbiomarkervalidation,itwas realised as necessary to cement the integration on a more permanent basis. This idea has become a major goal of the ECNIS2 project, funded by the Seventh Framework Programme of Research, with an ultimate goal of transforming network into a virtual centre, the European Centre for Research andEducationonCancer,EnvironmentandFood(ECRECEF). Coordinator: x NoferInstituteofOccupationalMedicine,ód,PL(Prof.KonradRydzyski) Otherbeneficiaries: Organisation Country GermanCancerResearchCentre,Heidelberg DE UniversityofCopenhagen DK KarolinskaInstitute,Stockholm SE InstituteforScientificInterchangeFoundation,Torino IT NationalHellenicResearchFoundation,Athens EL UniversityofLeicester UK NationalInstituteofEnvironmentalHealth,Budapest HU NicolausCopernicusUniversity,CollegiumMedicumin PL Bydgoszcz IT GeneticsResearchInstitute&OspedalePoliclinics,Milano JohannesGutenbergUniversity,Mainz DE FinnishInstituteofOccupationalHealth,Helsinki FI FreeUniversityofBrussels BE LundUniversity SE CatholicUniversityofLeuven BE InstituteofCancerResearch,Sutton UK MaastrichtUniversity NL BiochemicalInstituteforEnvironmentalCarcinogens, DE Prof.Dr.GernotGrimmerFoundation,Grosshansdorf ES CatalanInstituteofOncology,Barcelona UtrechtUniversity NL UniversityofDundee UK InternationalAgencyforResearchonCancer,Lyon FR NETIXSkrzypczynski,KrzysztofowiczSp.J.,Warsaw PL LeocordiaAB,Stockholm SE ImperialCollegeofScience,TechnologyandMedicine,London UK 111 112 CONTRACTNUMBER:514000 PROJECTTYPE:Integratedproject TOTALPROJECTCOST:€18321182 ECCONTRIBUTION:€14259966 STARTINGDATE:June1,2005 ENDDATE:December31,2009 DURATION:55months EUROPREVALL THEPREVALENCE,COSTANDBASISOFFOOD ALLERGYACROSSEUROPE Summary: 6 TheEUROPREVALL consortiumcomprised63 partners from 19 different countries and collaborating centres in North America, Australia and New Zealand. The project soughttoidentifyhowmanyindividualssufferfromfoodallergyandwhicharethe majorproblemfoods.Forthispurpose,cohortsweresetupindifferentagegroups with a birth cohort with complimentary community surveys in schoolage children and adults. Studies in unselected populations were complimented by a cross sectional study in the allergy outpatient clinics. This provided the project with a cohortofindividualswithwellcharacterisedfoodallergies,whichwerenecessaryfor developing and validating new diagnostic tools and led to the development of the EUROPREVALL Serum Bank (EPSB). All the datacollectedintheEuropeancohortstudies was entered online into databases. Information on how much of a food can cause a reaction has been collected when determining the clinical reactivity to foods, which has been assessed in the EUROPREVALLcohortswhereverpossible.Theroleofdiet,environmentandgenetic factors in food allergy was studied by characterising patterns of sensitisation to inhalant allergens in the cohorts with pollen exposure and food consumption patterns,ultimatelywithaviewtolinkingtheresultingdatasetstoidentifypotential causallinksbetweenexposuretopollenanddevelopmentoffoodallergies.Apilot study was carried out to establish prevalence of three infections that have been linkedtoprotectionagainstthedevelopmentofallergies:hepatitisA,toxoplasmosis andsalmonella.ExposuretothepriorityfoodsinEUROPREVALL(consumption)was evaluated in four countries. Changes in consumption were analysed in the four countries with peanut as the study focus. In addition to research, the consortium undertookmanytraininganddisseminationactivities. Potentialcontributiontothefollowingpolicies: x x x European Environment and Health Strategy [COM(2003) 338] and Action Plan 20042010"[COM(2004)416] EUhealthpolicyandprevention Directive2000/13/EContheapproximationofthelawsoftheMemberStates relatingtothelabelling,presentationandadvertisingoffoodstuffs EUfunding: x 'Foodqualityandsafety'thematicpriority 6 www.europrevall.org 113 Mainresults: x x x x x x x x x x EUROPREVALLwasanimportantprojectforpatientsasithasprovidedinsight ofallaspectsof (IgEmediated)foodallergiesandaddressedtheneededdata andgaps; AkeycontributionofEUROPREVALLwastheprovisionofgoodqualitydatato characterise the risk from allergenic foods. Epidemiological data are already providingaclearerpictureofthesizeofthepopulationatriskinEuropeandan indication of the relative importance of different foods. Data from the birth cohorts and particularly the clinic surveys are already revealing distinctive patternsoffoodallergyprevalence; Significant amounts of data on thresholds of reactivity to different allergenic foodsarenowemerging.Thesedataarenowbeingusedtodevelopandrefine dosedistributionmodelsforseveralfoods.Betterknowledgeofthenumbers atriskfromdefinedamountsofallergenicfoodwillnotonlyprovideasounder scientificbasisforregulatoryandallergenmanagementdecisions,butwillalso inform the wider debate among stakeholders, for instance on issues such as tolerablerisk; Acorrectdiagnosisisessentialforthefoodallergicpatient.Foodallergiescan result in uncomfortable, severe or potentially fatal responses. EUROPREVALL dataandknowledgewillhavesignificantimpactondiagnostictestingforfood allergyatseverallevels; TheprojecthasformedanetworkofpanEuropean(andbeyond)researchers spanningdisciplinesfromepidemiologytoeconomics,frommoleculargenetics to clinical science, risk management to food science. This is unique and necessary to realise the potential of the data and resources, in particular to ensureitsdeliveryinaform,whichcanbeusedbyriskassessorsandmanagers; ThedatafromEUROPREVALLprovideasignificantadvance,butstillneedstobe translated into validated evidence methods for risk management that can be usedeffectivelybythefoodindustrytomanageallergensinfoods.Aseriesof “stateoftheart”papersrelatingtofoodallergymanagementwasdeveloped; The socioeconomic impact of food allergy focused on assessing the role of food allergen labelling in communicating with food allergic consumers about potential allergenic hazards in particularly prepackaged foods, together with newstudiesonimpactoffoodallergiesonqualityoflifeandassessingitscost; EUROPREVALL partners have pioneered the development of the first disease specificqualityoflifeinstrumentsforfoodallergy; Validatedquestionnaireshavebeendevelopedtoassesstheeconomicimpact offoodallergies; Dissemination to different stakeholders has been undertaken though collaboration with other projects. The main EUROPREVALL activity has been focussed on the food industry, making use of a previously developed web basedplatform,www.foodallergens.info,todisseminatetoolsandinformation. It has links to the InformAll database and is linked to the MoniQA food allergensworkinggroupwebsite; 114 x x x Industrialinteractionshaveincludedactiveinvolvementoffoodmanufacturers through the participation of Unilever, Nestle and Kraft in many aspects, but particularly the development of realistic food challenge materials and development of tools and approaches to help the food industry manage allergens in foods. SMEs have also played an important role, e.g., in the developmentofimmunoassaystodetermineallergensinfoods; 33PhDstudentsweretrained,integratedacrosstheprojectactivitiescoupled with specific training in the study and clinical protocols of the multicentre studies; There has been a significant increase in the numbers of credible clinical researchcentresabletoundertakeeffectivediagnosisoffoodallergy. Coordinator: x InstituteofFoodResearch,Norwich,UK(Prof.ClareMills) Otherbeneficiaries: Organisation SanquinBloodSupplyFoundation,Amsterdam King'sCollegeLondon WageningenUniversity CharitéUniversityMedicalCenter,Berlin UniversityofZürich HospitalClinicoSanCarlosdeMadrid NationalInstituteforAgriculturalResearch(INRA),Paris TechnicalUniversityofDenmark,KongensLyngby Agrotechnology&Foodlnnovations,Ijmuiden PaulEhrlichInstitute,Langen RothamstedResearchLimited,Harpenden UnileverUKCentralResourcesLimited,Sharnbrook NESTECSA,Vevey KraftFoodsR&D,Munich MedicalUniversityofVienna NationalandKapodistrianUniversityofAthens UniversityofSouthampton EuropeanFederationofAllergyandAsthmaPatientsAssociations (EFA),Brussels UniversityMedicalCentre,Utrecht EurohandelsinstitutGMBH,Köln TepnelBiosystemsLTD,Deeside BiomayAG,Vienna lnstituteofAnimalReproductionandFoodResearch,Olsztyn AarhusSchoolofBusiness VBCGenomicsBioscienceResearchGmbh,Vienna UniversityofEastAnglia,Norwich 115 Country NL UK NL DE CH ES FR DK NL DE UK UK CH DE AT EL UK BE NL DE UK AT PL DK AT UK InteruniversitaryConsortiumforMagneticResonanceof ParamagneticMetalloproteins,SestoFiorentino GroningenUniversityHospital AgriculturalUniversityofAthens NationalResearchCouncil(CNR),Rome MedicalUniversityofód TheCentralManchesterandManchesterChildren'sUniversity HospitalsNationalHealthServiceTrust PhadiaAB,Uppsala ReflabAPS,Copenhagen AnaphylaxisCampaign,FarnboroughHampshire MedicalUniversity,Sofia FacultyHospitalBulovka,Prague VilniusUniversity BaigentLtd,Chesham IPPragmatics,TheLondonBioscienceInnovationCentre London NetherlandsAnaphylaxisNetworkFoundation,Dordrecht LeidenUniversityMedicalCentre SanCarloClinic,PadernoDugnano MaastrichtUniversity StrasbourgUniversityHospital LandspitaliUniversityhospital,Reykjavik LaPazUniversityHospital,Madrid HelmholtzResearchCentreforEnvironmentalHealth,Munich RoguchiMemorialInstituteforMedicalResearch,Accra HospitalityandLeisureManpower,KingstonUponThames HospitaloftheHospitallerBrothersofStJohnofGod,Budapest UniversityCollegeCork AcademicMedicalCentreofUniversityofAmsterdam ImperialCollegeofScience,TechnologyAndMedicine,London FoodInformationServiceEurope,BadBentheim AllergyAsthmaAssociates,Mysore SiberianStateMedicalUniversity,Tomsk ChineseUniversityofHongKong IALAutomationundLogistikGMBH,Rötgen FoundationforBiomedicalResearchatRamonyCajalUniversity Hospital,Madrid AppelEuropa,Sofia CentreforEnergy,EnvironmentandTechnologyResearch (CIEMAT),Madrid MedicalUniversityofód JagiellonianUniversityMedicalCollege,Cracow AarhusUniversity 116 IT NL EL IT PL UK SE DK UK BG CZ LT UK UK NL NL IT NL FR IS ES DE GH UK HU IE NL UK DE IN RU CN DE ES BG ES PL PL DK CONTRACTNUMBER:513953 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€2593200 ECCONTRIBUTION:€1750800 STARTINGDATE:December1,2004 ENDDATE:May31,2008 DURATION:42months FOODANDFECUNDITY PHARMACEUTICALPRODUCTSAS HIGHRISKEFFECTORS Summary: The strategic objectives of the FOOD & 7 FECUNDITY project were to (i) identify potential endocrine disrupters among pharmaceutical products (PPs);(ii)developandemployvalidatedmethods(chemicaland immunochemical) for screening and testing PPs in environmental and food samples; (iii) determine their adverse effects and mechanism of action at the cellular, molecular and whole organism level; (iv) learn the extent of human exposure to the selected PPs; and (v) assess, based on the data accumulated in the course of the study, their risk to men and women fecundity in various geographical locations and exposure scenarios in Europe. The project first carried out a feasibility study to identify potentially highrisk PPs and develped an antibody as well as an enzyme linked immunosorbent assay (ELISA) for one of them [ethynylestradiol (EE2)]. An inventory was prepared of pharmaceuticals with a potential to affect human fecundityviaexposurethroughthehumanfoodchain.Classificationofmechanisms by which pharmaceuticals affect fecundity was prepared. Exposure pathways for human exposure to PPs through food were analysed and the main pathways identified.StrategiesweredevelopedforthegenerationofantibodiesandELISAsfor sevenhighpriorityPPs: ethynylestradiol(EE2),medroxyprogesteroneacetate(MPA), levonorgestrel (LNG), indomethacin (IMT), atenolol (ATL), trimethoprim (TMP) and fluoxetine (FLX). Methods were developed and optimised for the clean up and concentrationofEE2andLNGfromrealenvironmentalsamples,foodandbiological samples. The feasibility of studying unintended exposure to PPs in human serum sampleswasdemonstrated.HumanexposuretoEE2andasourceofenvironmental contaminationthatmayeffecthumanreproductionwereidentified. Potentialcontributiontothefollowingpolicies: x x x x Directive2000/60/ECestablishingaframeworkforCommunityactioninthe fieldofwaterpolicy EuropeanEnvironmentandHealthStrategy[COM(2003)338] Directive2004/27/ECamendingDirective2001/83/EContheCommunitycode relatingtomedicinalproductsforhumanuse Directive2004/28/ECamendingDirective2001/82/EContheCommunitycode relatingtoveterinarymedicinalproducts EUfunding: x 'Foodqualityandsafety'thematicpriority 7 http://foodandfecundity.factlink.net 117 Mainresults: x Feasibility study: consisted of (i) identification of the first potential high risk PPs;(ii)generationofanantibodyforoneofthem:ethynylestradiol(EE2);(iii) DevelopmentofanELISAforEE2;(iv)characterisationoftheEE2antibodies; x Identification of potential endocrinedisrupting chemicals: An inventory has been prepared of pharmaceuticals with a potential to affect human fecundity viaexposurethroughthehumanfoodchain.Theclassificationofmechanisms by which pharmaceuticals affect fecundity, i.e., what kind of reproductive disorder they may cause, was completed. An evaluation of the risk assessment/statistical models was performed in order to select the most suitable ones and to adapt them to the needs of the project. Exposure pathwaysforhumanexposuretoPPsthroughfoodhavebeenanalysedandthe mainpathwaysidentified; x Diagnostic assays and validation of assays: Strategies were developed for the generationofantibodiesandmicroplateassays(ELISAs)forsevenhighpriority PPs:EE2,MPA,LNG,IMT,FLX,TMPandATL.Fiveoftheaboveantibodieswere characterised(antiEE2,antiMPA,antiLNG,antiIMTandantiATL.)foraffinity, limit of detection and cross reactivity. The ability of the EE2, IMT, and LNG diagnosticassaystomonitorthetargetPPsinenvironmental,foodandhuman serumsampleswasevaluated.Acellbasedreceptorbindingassayprotocolwas developed, which can be easily converted into a functional highthroughput screening assay. Methods were developed and optimised, based on solgel immunaffinity purification in combination with solidphase extraction, for cleanup and concentration of EE2 and LNG from real environmental samples (water of different sources), food (cow milk) and biological samples (human serum and breast milk) at high recoveries and full compatibility with liquid chromatography–mass spectrometry (LCMSMS). Environmental (water from different sources) and human serum samples were prepared for LCMSMS analysisinordertodeterminepopulationexposure; x Monitoring PPs in human, food & environmental samples: 299 human serum samplesfromDenmarkwereanalysedbythecombinedAIPLCMSMSmethod forEE2.Inpartofthesamplesdetectableamountswerefound; x Clinical epidemiology: The feasibility of studying unintended exposure to pharmaceutical compounds in human serum samples was demonstrated. HumanexposuretoEE2andasourceofenvironmentalcontaminationthatmay effecthumanreproductionwereidentified. 118 Coordinator: x AnalystResearchLaboratoryLtd,Rehovot,IL(Dr.HaimSchlesinger) Otherbeneficiaries: Organisation Country TheVolcaniCenter,BetDagan IL AarhusUniversityHospital DK NationalInstituteofHealthandMedicalResearch(INSERM), FR Paris NationalInstituteforAgriculturalResearch(INRA)andNational FR CentreforScientificResearch(CNRS),Nouzilly NationalInstituteforPublicHealthandtheEnvironment(RIVM), NL Bilthoven WessexInstituteofTechnology,Southampton UK AT FactlineWebservicesGmbH,Vienna OSMDANLtd,Rehovot IL 119 120 CONTRACTNUMBER:44393 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€1620460 ECCONTRIBUTION:€1500000 STARTINGDATE:January1,2007 ENDDATE:December31,2009 DURATION:36months FURANRA ROLEOFGENETICANDNONGENETIC MECHANISMSINFURANRISK Summary: After the discovery of the formation of acrylamide during heat processing of food, more recent studies have also indicated that the simple organic molecule furan is present in a wide variety of foods and may also be formed during heat processing. Like acrylamide, furan until recently has also been known only as an industrial chemical and most of the toxicity data elaborated up to now are not a suitablebasisfortherequireddetailed risk assessment of human exposures to furan with food. Since the mechanismsofcarcinogenicactivityof furan in rodents are not well understood, the objectives of FURANRA were to generate relevant mechanistic informationasasupportfortheongoingriskassessmentofhumanfuranexposures with food. The importance of modeofaction research on furan is underscored by thecomparativelysmalldifferenceintheestimatedhumanexposuresandthedoses of furan, which cause carcinoma in the liver of experimental animals. A detailed elucidation of genotoxic and nongenotoxic mechanisms and their possible dose response relationships and interconnectivity are of fundamental importance for a reliableriskassessment.DuetogenotoxicityandDNAbindingoffuranestablishedin the project, the current risk assessment for furan requires application of a linear doseresponse relationship. Exposures to furan in adults are estimated to be less than0.5g/kgbodyweight/day;datafromthisprojectalsosupportasimilarintake of furan in children. Due tothe high incidence of tumours induced by furan in rats evenatthelowestapplieddose,alinearextrapolationoftheanimaldatatocalculate possible human tumour risks is uncertain. When using a marginofexposure (MoE) assessment,MoEstoadoseinducingasignificanttumourincidencearecalculatedas only1000to2000.ThelowMoEswarrantfurtherreductionsinfuranexposures.A 8 detailedreportcanbedownloadedfromtheprojectwebpage (Deliverable9.1). Potentialcontributiontothefollowingpolicies: x x Council Regulation (EEC)315/93 laying down Community procedures for contaminantsinfood;CommissionRegulation(EC)1881/2006settingmaximum levelsforcertaincontaminantsinfoodstuffs EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Scientificsupporttopolicy'programme 8 www.furanra.toxi.uniwuerzburg.de 121 Mainresults: x A 28day repeated dose study with oral dosing of furan showed minor liver damage induced by furan both in rats and in mice, but analysis ofthetissues andbloodsamplesalreadyindicatedchangesingeneexpressionandbileacid excretion; x In vivo and in vitro genotoxicity studies showed equivocal results with furan itself, but a clear response with the reactive furan metabolite, when added directlytothecellculturemedia; x Furanconcentrationsshowawiderangeinfood; 14 x Treatment of male Fischer rats with Cfuran at a known carcinogenic dose indicatedthatfuranmaybindtoDNA; x No overt signs of liver toxicity were evident by histopathology, clinical chemistry and metabonomics after oral administration of furan for 28 days. However, a dosedependent increase in cell proliferation was detected specificallyinareaslocatedneartheedgeoftheliverlobes; x In vivo genotoxicity assays in B6C3F1 mice provided evidence of genotoxic effects after repeated oral exposure with furan (a doserelated increase of micronuclei). Repeated oral furan administration was shown to induce in vivo primary DNA damage in spleen cells, which evolved in doublestrand breaks followingmitogenstimulationofcellsinvitro; x Furan induced a doserelated increase in thymidine kinase (tk) mutation frequencyinL5178Ycells,butathighcytotoxicdoses; x ElevatedfuranlevelswerefoundincarrotjuiceswithrelativelyhighpHvalues andinprunejuices.Otherflavoursofthebrandsthathavehighfuranlevelsin theircarrotorprunejuiceshadlowfuranlevels.Caroteneincombinationwith sterilisation is a possible source of furan in carrot juices. The prune drying process is a possible source of furan in prune juices. Babies may have high exposure to furan when their carrot juice consumption is high (0.25 litre per day).Adultsarenotatriskwhenconsumingcarrotorprunejuices; x Furan determination in bakery products turned out to be irreproducible, possibly because of inhomogeneous furan distribution in the products. The highestfuranlevelswerefoundinwholegrainproducts; x Chemical characterisation of furan metabolites in bile provided further evidence to suggest that glutathione (GSH)conjugates and degraded protein adducts are major in vivo metabolites of furan. Although no toxicity data are availablesofar,themetabolitesidentifiedinbileareassumedtobelesstoxic thancis2butene1,4dialandtheinitialmonoGSHconjugate; x Onthebasesoftheresultsobtained,furanprovedtobeaninvivogenotoxinin ratsunderthereportedexperimentalconditions,thoughin“nonconventional” genotoxicityassays. 122 Coordinator: x UniversityofWürzburg,DE(Prof.WolfgangDekant) Otherbeneficiaries: Organisation NationalHealthInstitute(ISS),Rome UniversityofKaiserslautern UniversityofBirmingham UniversityofTuscia,Viterbo VUUniversity,Amsterdam EcoTraceLimited,Camberley NestléResearchCentre,Lausanne 123 Country IT DE UK IT NL UK CH 124 CONTRACTNUMBER:18996 PROJECTTYPE:Integratedproject TOTALPROJECTCOST:€13258334 ECCONTRIBUTION:€11327585 STARTINGDATE:March1,2006 ENDDATE:August31,2010 DURATION:54months GABRIEL MULTIDISCIPLINARYSTUDYTOIDENTIFY THEGENETICANDENVIRONMENTAL CAUSESOFASTHMAINTHEEUROPEAN COMMUNITY Summary: 9 The aim of GABRIEL was to systematically discover and identify the environmental and genomic causes of asthma with largescale studies of genes and environment. Genomewide association studies showed that allergy is a consequence of asthmaratherthanitscauseand identified several new targets for asthma therapy. A panel of 100keygeneticmarkershasbeentypedinafurther40000subjectsfrompopulation samples across Europe in very substantial epidemiological survey. GABRIEL has performed searches for factors protective against asthma through advanced epidemiological surveys of rural populations, with an initial sample size of 135 000 children. The results confirm the protective effect of farming, and show that farm childrenwereexposedtoawiderrangeofmicrobialexposurethancontrolchildren. GABRIEL scientists have been the first to show that the airways contain a characteristicmicrobialflorawhichdiffersbetweenhealthanddisease.Inaddition, GABRIELhasfosteredinnovativemolecularinvestigationsfactorsinfluencingasthma and set out to discover the molecular nature of strong protective effect against asthma conferred by farming environments. EMC Microcollections have patented highlysensitiveassaysfortheidentificationofbacteriallipoproteinsindustextracts, and have patented a strategy for the synthesis of new ligands as potential therapeuticagentsforasthmaprevention. Potentialcontributiontothefollowingpolicies: x EuropeanEnvironmentandHealthStrategy[COM(2003)338] x EuropeanEnvironment&HealthActionPlan20042010"[COM(2004)416] x EUhealthpolicyandprevention EUfunding: 'LifeSciences,GenomicsandBiotechnologyforHealth'thematicpriority x 9 www.gabrielfp6.org 125 Mainresults: x GABRIEL has produced and published novel investigations into the ethics of geneticstudiesofyoungchildren,bydistributingquestionnairesandsampling children’sopinionthroughonlinefocusgroups; x ThegeneticstudiesinGABRIELwereextraordinarilysuccessful,culminatingina secondgeneration genomewide association study (GWAS) of 15 billion genotypesin10000casesofasthmaand16000controls.Thisstudydiscovered several new asthma genes, showing that allergy is a consequence of asthma rather than its cause and identifying several new targets for asthma therapy. The results have been published in the New England Journal of Medicine in 2010,addingtoapublicationinNatureofthefirstasthmaGWASin2007.The results of the GABRIEL GWAS are now the principal component of an internationalmetaanalysisof25000asthmatics,tobecompletedin2011; x TheGABRIELconsortiumhasalsocompletedaverysubstantialepidemiological surveyinwhichapanelof100keygeneticmarkershasbeentypedinafurther 40000subjectsfrompopulationsamplesacrossEurope.Analysisofthisdatais ongoing, including systematic analyses of geneenvironment interactions with cigarettesmoking,farmingenvironments,obesityandairpollution; x GABRIELhasperformedsearchesforfactorsprotectiveagainstasthmathrough advanced epidemiological surveys of rural populations, with an initial sample size of 135 000 children. The results confirm the protective effect of farming, and show that farm children were exposed to a wider range of microbial exposurethancontrolchildren;thisexposurecanexplainasubstantialfraction of the inverse relation of asthma status and farming. These results were publishedintheNewEnglandJournalofMedicinein2011; x Surveys of 10 000 children have also been completed in SouthWest Poland. Theenvironmentalandgenomicfactorsthatcauseorprotectagainstasthmain different nonEuropean populations, including subjects from Russia, Chinese populations and rural and urban populations in tropical Ecuador, were examined; x GABRIELhasfosteredinnovativemolecularinvestigationsofGABRIELsubjects, including proteomic investigation of serum from the children of farmers and nonfarmers. Affymetrix and Illumina platforms have been used to measure global gene expression in RNA from lymphoblastoid cell lines (LCL) from childrenintheMRCAandMRCEfamilypanels.Thefirstresultswerereported in Nature Genetics in 2007, and contributed to the 1 000 genome project papersinNatureandSciencein2010.Furtheranalysisofthisimportantdataset isongoing; 126 x x x x x GABRIEL has carried out highly novel assessments of microbial and other factorsindustandfarmmilk,whichmaycontainthefactorsthatconferstrong protectionagainstasthmaintheruralandfarmingenvironment.GABRIELhas also used genomic studies as a systematic tool to classify and identify the microbial flora from environmental samples, from the upper airways of asthmatic and normal children, and from bronchoalveolar lavage of children withsevereasthmaandcontrols; The secondgeneration GWAS of asthma included 600 subjects with occupationalasthma,andidentifiedseveralsignificantgeneticeffectsthatare currentlybeingmodelledforgeneenvironmentinteractions; GABRIEL also set out to discover the molecular nature of strong protective effectagainstasthmaconferredbyfarmingenvironments.Dustobtainedfrom mattresssockswastestedforeffectsoninflammationinairwayepithelialcells, inamodelofdendriticcell/Tcell(DC/T)interaction,andinamurinemodelof asthma.Strongprotectiveeffectswereobserved,andfractionationofthedust extracts has narrowed the search for biological molecules that may be used therapeuticallytopreventasthma; GABRIELfundedsixfellowshipsforyoungscientiststospendseveralmonthson anexchangevisittoahostlaboratorywithintheconsortium; The training programme organised numerous workshops and meetings of specialinterestgroups. Coordinator: x Imperial College of Science, Technology And Medicine, London, UK (Prof.WilliamCookson) Otherbeneficiaries: Organisation Country MunichUniversityChildren'sHospital DE NationalCentreforGenotyping,Evry FR EuropeanCommission,JointResearchCentre,Ispra IT KarolinskaInstitute,Stockholm SE ResearchCentreBorstel DE UniversityofUlm DE UniversityofBasel CH StGeorge's,UniversityofLondon UK UtrechtUniversity NL CharitéUniversityMedicalCenter,Berlin DE NL LeidenUniversityMedicalCentre UniversityCollegeCork IE InstituteofAppliedScientificResearch(TNO),Leiden NL RuhrUniversity,Bochum DE 127 UniversityofNaturalResourcesandAppliedLifeSciences, Vienna NationalInstituteforHealthandWelfare(THL),Kuopio UniversityofFrancheComté,Besançon UniversityofGroningen,UniversityMedicalCenter UniversityofOxford WroclawMedicalUniversity EMCMicrocollectionsGmbH,Tübingen AarhusUniversity,Aarhus UniversityofBristol,AvonLongitudinalStudyofParentsand Children SurfaceTherapeutics,Oxford HelsinkiUniversityCentralHospital SiberianStateMedicalUniversity,Tomsk HelmholtzResearchCentreforEnvironmentalHealth,Munich UniversityofVerona NationalInstituteofHealthandMedicalResearch(INSERM), Evry InstituteofBiochemistry&Genetics,Ufa InstituteofMedicalGenetics,Tomsk ChineseUniversityofHongKong UniversidadSanFranciscodeQuito 128 AT FI FR NL UK PL DE DK UK UK FI RU DE IT FR RU RU CN EC CONTRACTNUMBER:506378 PROJECTTYPE: NetworkofExcellence TOTALPROJECTCOST:€14400000 ECCONTRIBUTION:€14400000 STARTINGDATE:February1,2004 ENDDATE:January31,2010 DURATION:72months GA2LEN GLOBALALLERGYANDASTHMA EUROPEANNETWORK Summary: 10 GA²LEN was a Network of Excellence of the leading European clinical and research facilities in the field of allergology and asthma, associated with the European Academy of Allergy and Clinical Immunology (EAACI) and the organisation representing European patientswithallergiesandasthma(EFA). ItstartedundertheEUSixthFramework Programme as a Network of Excellence. Itbroughttogetherepidemiological,basicandclinicalresearchersfromacrosstheEU to work on common activities. The results have been published widely. GA²LEN allowed for allergic diseases and asthma to be tackled using a global approach, startingfromcoprogrammingandfacilitatingbasicresearch,acceleratingtheresults fortranslationalresearch,optimisingmultinationalclinicalresearch,butnotstopping there.GA²LENhassystematicallycreatedorupdatedrelevantguidelinesforallmajor topicsinallergy,togetherwiththeEAACI.GA²LENhasensuredtheharmonisationof the standards of care and through its quality programme certifies the member institutions to comply to the highest standards. GA²LEN has achieved sustainability andiscontinuingasanonprofitnetwork,buildingonthefoundationprovidedbythe sixyearsofFP6funding.Thisnetwork,GA²LENe.V.,isbasedattheCharitéHospital in Berlin. GA²LEN provides continuous support to EU initiatives, but is currently seeking additional funding not onlyfor the durable structure, but also to allow the outputsneededtoofferpanEuropeansurveillanceonallergiesforEUpolicies. Potentialcontributiontothefollowingpolicies: x x x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EuropeanEnvironment&HealthActionPlan20042010"[COM(2004)416] EUhealthpolicyandprevention EUfunding: x 'Foodqualityandsafety'thematicpriority 10 www.ga2len.net 129 Mainresults: x GA²LENwascreatedtocombatfragmentationintheEuropeanallergy/asthma research, in order to ensure excellence in research by bringing together institutions and researchers from across the EU. The network notably put in place centralised structures and an office supervising the multiple assets in knowledge of the different GA²LEN partners, enabling them to optimally synchronisetheirresearchefforts.Creatingthesestructureswascomplexsince notonlymanytechnical,ethicalandlegalaspectshadtobesolved,butalsoa wholenewatmosphereoftrusthadtobecreated.Currently,GA²LEN’svisionis stilltoreducetheburdenofallergicdiseasesinEuropebyimprovingthehealth ofEuropeanswithallergicdiseasesaswellasbyincreasingthecompetitiveness andtheinnovativecapacityofEUhealthrelatedindustriesandbusinesses; x WorkcarriedoutbyGA²LENhas(i)establishedtheEUasaleaderinthefieldof allergy and asthma research and clinical care; (ii) proposed avenues for reducing the socioeconomic impact of allergy and asthma for the EU; (iii) started to improve the quality of life and availability of treatment for allergy patients; x GA²LEN has worked and continues working within the research community through(i)thecoordinationandcombinationofexisting,fragmentedEuropean forces from epidemiology, basic, clinical and social sciences; (ii) the establishment of an open platform for joint activities, including common databases, biobanks and modern communication facilities; (iii) the establishmentofaclinicaltrialsnetworktotestnovelmanagementstrategies in the field of allergy (including diagnostic, treatment and preventive strategies); (iv) the assistance to researchers in accessing complementary expertise and tools; (v) the development of common training schemes for young scientists (both clinical and nonclinical) and exchange fellowships to facilitate international, multidisciplinary and crosscultural development; (vi) the promotion of integration between academia and industry, in particular smallandmediumsizedenterprises(SMEs); x The network connects the research community and the rest of the society through(i)theincorporationofpatients’viewsintotheformulationofresearch policy; (ii) the incorporation of policy makers’ views into the formulation of research policy; (iii) the development of mechanisms to disseminate informationtoallstakeholders;(iv)thedevelopmentofapanEuropeansystem of quality management for allergy services; (v) the assistance with the development of evidencebased policies for the prevention and management ofallergyandasthma; x During the fourth year, the largest multinational database in birth cohorts worldwide was created by joining together nearly all existing data in Europe. Thisoffersthestatisticalpowertoaddressimportantquestions,andtheresults havebeenpublished; x Over500paperswereproducedbyGA²LENmembers.Amongthem,about80 paperswerepublishedasGA²LENpositionpapers,practicalguides,or“GA²LEN taskforcepapers”withGA²LENinthetitle; 130 x x The project organised a large number of events (symposia, workshops, conferences), schools, training, public meetings, awareness raising, press releasesandotherformsofdissemination; GA²LENhasproposedtosetupasentinelnetworktomonitoremergingtrends inallergicdiseaseEUwideusingGA²LENpartnercentresas“sentinels.” Coordinator: x UniversityofGhent,BE(Prof.PaulvanCauwenberge) Otherbeneficiaries: Organisation EuropeanAcademyofAllergologyandClinicalImmunology (EAACI),Brussels EuropeanFederationofAllergyandAsthmaPatients Associations(EFA),Brussels UniversityofViennaMedicalSchool OdenseUniversityHospital HelsinkiUniversityCentralHospital NationalInstituteofHealthandMedicalResearch(INSERM), Villejuif CharitéUniversityMedicalCenter,Berlin LudwigMaximiliansUniversity,Munich TechnicalUniversityMunich NationalandKapodistrianUniversityofAthens UniversityofPalermo NationalResearchCouncil(CNR),Rome UniversityofGenoa AcademicMedicalCentreofUniversityofAmsterdam UtrechtUniversity VoksentoppenBKL,RikshospitaletUniversityClinic, UniversityofOslo JagiellonianUniversityMedicalCollege,Cracow MedicalUniversityofód UniversityofCoimbra MunicipalInstituteofMedicalResearch(IMIMIMAS),Barcelona AutonomousUniversityofMadrid UniversityofGothenburg KarolinskaInstitute,Stockholm SwissInstituteofAllergyandAsthmaResearch,Zürich NationalHeartandLungInstitute,London UniversityofSouthampton 131 Country BE BE AT DK FI FR DE DE DE EL IT IT IT NL NL NO PL PL PT ES ES SE SE CH UK UK 132 CONTRACTNUMBER:036337 PROJECTTYPE: NetworkofExcellence TOTALPROJECTCOST: €12400000 ECCONTRIBUTION:€12300000 STARTINGDATE:February1,2007 ENDDATE:January31,2012 DURATION:60months MONIQA TOWARDSTHEHARMONISATIONOF ANALYTICALMETHODSFORMONITORING QUALITYANDSAFETYINTHEFOODCHAIN Summary: The reasons for setting up the MONIQA network of excellence included, inter alia, thefragmentationEuropeanresearchinfoodsafetyandquality;introductionofnew EU regulations on food allergens, mycotoxins and other food contaminants; poor communication between research and standardisation bodies; limited validity of standardisation/validation certificates for analytical methods; lack of appropriate validationprotocolsfornewandrapidmethods;absenceofreferencemethodsand materials for some analytes (e.g., food allergens);andlackofwaysofassessing thefinancialimpactofneworamended legislation at the micro or macro socioeconomic level. To address these issues, The Network of Excellence sought to ensure longlasting cooperation amongst leading research institutions, industrial partners and the small and mediumsized businesses that dominate European food manufacture and retail. The network undertook a large number of activities, including (i) Coordinating and merging of research infrastructures (e.g., settingupofadatabaseofresearchinfrastructureresources,clarifyingthetermsand conditionsforinfrastructuresharinganddevelopingscenariosforthesharingofsaid infrastructure); (ii) Promoting personnel exchanges and mobility; (iii) Carrying out training activities and joint research; (iii) Pursuing network sustainability: Legal agreement has been concluded to create the MONIQA Association. This nonprofit organisation will continue the Network of Excellence activities as well as offering servicesandproductsforthefoodindustry,analyticallaboratories,andpolicymakers andregulators.Moredetailsontheprojectoutcomeandachievementscanbefound 11 onthewebsite . Potentialcontributiontothefollowingpolicies: x Council Regulation (EEC)315/93 laying down Community procedures for contaminantsinfood;CommissionRegulation(EC)1881/2006settingmaximum levelsforcertaincontaminantsinfoodstuffs EUfunding: x 'Foodqualityandsafety'thematicpriority 11 www.moniqa.org 133 Mainresults: x The Network of Excellence has involved experts from around the globe and aimedtomakefoodssaferbyharmonisingworldwidefoodqualityandsafety monitoring and control strategies. Participants and stakeholders included control and reference laboratories, industrial and research laboratories, method providers and test kit manufacturers, food manufacturers and food related associations, universities and higher education institutions, and policy makers; x MONIQA focused on the validation of and the setting of performance criteria/requirementsformethodsusedtoanalysefoodsand/orproductsafety and quality. The main emphasis was on rapid methods and emerging new testingtechnologies,andtheirapplicabilityandreliabilityinroutinetesting; x Concerns related to the different legislation/regulations and practise in issues such as sampling and measurement uncertainty in Europe and other regions and countries (e.g., Americas, Asia) have been identified and problems associated with interpretation of analytical results and compliance criteria practiseconsidered; x The MONIQA database was set up, allowing rapid searching of relevant analyticalmethodsforspecificanalytes,includinginformationaboutthedegree ofvalidation,legalrequirementsandlimits,andtheavailabilityofmethods.The database is structured around two key elements: comprehensive lists of contaminantsandcommodities(ormatrices)inwhichcontaminantsmaypose a threat to human health. Detailed information about the methods database canbefoundatwww.moniqa.org/database; x MONIQA has managed international ring trials validating methods for regulatory and surveillance, supporting standardisation organisations around the globe, primarily the European Committee for Standardisation CEN, the InternationalOrganizationforStandardizationISO,andCodexAlimentarius; x The socioeconomic impact of food safety and quality regulations was one of themostimportantissuescoveredbyMONIQA.Theprojectaimedtosupport systematicassessmentofthesocioeconomicimpactofEuropeanfoodquality andsafetyregulationsintermsofefficiency,effectivenessandconsistency,and administrativecostsaswellasinternationaltradeamongststakeholders(e.g., consumers,industry,regulatoryandcontrolbodies)atdifferentlevels; x Examples of topics for food scientist training activities supported by MONIQA include the use of food analysis in managing food chemical contaminant risk withinthefoodindustry,foodsafetyandriskassessment,andcriteriaapproach formethodvalidationandriskcommunication; x Besidesfacetofaceworkshops,distancelearninghasbeenanimportantpart oftheMONIQAtrainingprogramme.MONIQAoffersdistancelearningviaweb seminarsandeLearningcourses; x Initially,prioritiesfortheMONIQA Association, whichhastakenoversomeof theactivitiesoftheNetworkofexcellence,willincludedisseminatingvalidated data for food safety through, for example, online databases; improving the knowledgebased bioeconomy through participation in relevant research 134 programmes and facilitating bilateral/multinational research collaboration agreements; promoting harmonisation of analytical approaches in food safety and quality; providing infrastructure for and establishing an international network for interlaboratory validation trials for analytical methods and referencematerials;andsharingexpertiseandunderstandingthroughtraining courses, scientific conferences and symposia, researcher mobility, expert consultancy,andpublications. Coordinator: x International Association for Cereal Science and Technology, Vienna, Austria (Dr.RolandErnestPoms) Otherbeneficiaries: Organisation Country UniversityofNaturalResourcesandAppliedLifeSciences, AT Vienna AinShamsUniversity,Cairo EG CampdenBRI,ChippingCampden UK CERGroupe,HormonologyDepartment,Marloie BE EurofinsAnalytikGMBH,Hamburg DE GaikerFoundation,Zamudio(Bizkaia) ES CentralScienceLaboratory,York UK InternationalQualityandEnvironmentServicesS.A.,Athens EL TR TubitakMarmaraResearchCenterFoodInstitute,GebzeKocaeli UniversityofFoodTechnologies,Plovdiv BG VocaltagLtd,MigdalHaemek IL VTTTechnicalResearchCentre,Espoo FI UniversityofNaples IT NorwegianFoodResearchInstituteMatforsk,Ås NO NationalTechnicalUniversityofAthens EL NL NationalInstituteforPublicHealthandtheEnvironment(RIVM), Bilthoven SichuanUniversity,Chengdu CN IT NationalResearchInstituteforFoodandNutrition(INRAN), Rome BudapestUniversityofTechnologyandEconomics HU InstituteofEnvironmentalScienceandResearch,Christchurch NZ NationalFoodandNutritionInstitute,Warsaw PL HacettepeUniversity,Ankara TR ChineseCerealsandOilsAssociation,Beijing CN ID InstitutePertanianBogor,Bogor HanoiUniversityofTechnology VT 135 InstituteofFoodResearch,Norwich InstituteofSciencesofFoodProduction(ISPA),Rome WebbStephenMatthew,Vienna EuropeanCommission,JointResearchCentre(JRC),Ispra UniversityofBonn InterdisciplinaryCentreforComparativeResearchintheSocial Sciences,Vienna UniversityofBologna 136 UK IT AT IT DE AT IT CONTRACTNUMBER:16320 PROJECTTYPE:Integratedproject TOTALPROJECTCOST:€15661101 ECCONTRIBUTION:€13594976 STARTINGDATE:February1,2006 ENDDATE:July31,2011 DURATION:66months NEWGENERIS DEVELOPMENTANDAPPLICATIONOF BIOMARKERSOFDIETARYEXPOSURETO GENOTOXICANDIMMUNOTOXICCHEMICALS ANDOFBIOMARKERSOFEARLYEFFECTS,USINGMOTHERCHILDBIRTHCOHORTS ANDBIOBANKS Summary: 12 NEWGENERIS studied maternal exposure during pregnancy to selected carcinogenic and immunotoxic chemicals and evaluated the exposures and effects on the foetus and in later childhood, particularly in relation with childhood cancer and immune disorders. The role of relevant exposures of the fathers was also evaluated. Selected biomarkers were measured in samples available in motherchild birth cohorts/biobanks in five Europeancountries.AcutelymphocyticleukaemiacaseswererecruitedinGermany and evaluated for genetic polymorphisms. A total of around 250 000 motherchild pairswereincluded.Newmotherchildcohortstudieswerelaunched,e.g.,theRHEA cohort in Crete. For the biomarkers of exposure investigated, clear differences between countries were observed. An association between increased prenatal exposurelevelstodioxinsandPCBsthroughmother’sfoodandincreasednumbersof upperrespiratorytractinfectionsandwheezeduringthefirstthreeyearsoflifewas found.Achemicalcontentdatabasewasconstructedandusedtocalculatethelevels ofmaternalchemicalexposures.Spermintegrityappearedtoberesilienttochemical exposureinvitro.Astrongassociationwasfoundbetweenincreasedacrylamideand glycidamideadductsandreducedbirthweightofchildren.Avalidatedexvivo/invitro system for the study of transport of selected genotoxicants and immunotoxic substances across the placental barrier was established and applied. The placenta barrierwasnotfoundtobeprotectivetowardsexposurestothestudiedcompounds. In vitro gene expression studies on human peripheral blood mononuclear cells resultedintheidentificationofgenesthatarederegulatedbyspecificcompounds.In addition to the scientific activities and publications, the project implemented a number of training activities and exchange programmes and undertook outreach activitiesincludingtheorganisationofworkshopsandotherevents. Potentialcontributiontothefollowingpolicies: x Council Regulation (EEC)315/93 laying down Community procedures for contaminantsinfood;CommissionRegulation(EC)1881/2006settingmaximum levelsforcertaincontaminantsinfoodstuffs x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Foodqualityandsafety'thematicpriority 12 www.newgeneris.org 137 Mainresults: Experimentswerecarriedoutusing12modelcompounds:benzo(a)pyrene(BaP),2 amino3methylimidazo [4,5f] quinoline (IQ), 2amino1methyl6 phenylimidazo[4,5b]pyridine(PhIP),monoacrylamide,dimethylnitrosamine(NDMA), aflatoxin, deoxynivalenol (DON), 2,3,7,8tetrachlorodibenzodioxin (TCDD), polychlorinatedbiphenyls(PCB),4hydroxynonenal,malondialdehydeandethanol. Dietaryexposureassessment: x Achemicalcontentdatabasewasconstructedandeventuallyusedtocalculate thelevelsofthematernalchemicalexposures,toprovideharmonisedexposure estimatescomparableattheEuropeanlevel; x Dataontheregionalvariationofthedietaryexposuresofpregnantwomenin Europetothetoxicchemicalsstudiedandtheirmaindietarydeterminants,as well as information on the dietary habits of pregnant women in different Europeanregions,havebeenproduced; x As regards acrylamide, significant geographic variation was observed, with Bradford showing the highest exposure and Norway, Spain and Crete the lowest. The main contributors to dietary acrylamide exposure are potato products(frenchfries,potatochipsandcrisps). Motherchildbirthcohortsandbiobanks: x During the first part of the project the project focused on (i) enrolling the pregnant mothers and securing adequate study procedures; (ii) collection of questionnairedataincludingfoodfrequencyquestionnaires;and(iii)obtaining biologicalsamples; x Amajorachievementwasthelaunchingofnewstudies,e.g.,theRHEAmother childcohortinCrete; x This work has been further exploited in other EUfunded projects such as 13 14 15 HIWATE ,ENVIROGENOMARKERS ,andESCAPE ; x Astrongassociationwasfoundbetweenincreasedacrylamideandglycidamide adductsandreducedbirthweightofchildren.Theseresultsareimportantfor publichealth,becauseriskfactorsforsignificantreductionsinbirthweighthave rarelybeenidentified; Paternalimpact: x ProtocolsforquantifyingDNAstrandbreaksonthebaselinelevelsandafterin vitroexposuretothetwelvetestcompoundsofspermatozoaandlymphocytes wereestablishedusingtheCometassay; x Sperm integrity appears to be resilient to chemical exposure and ionising radiation in vitro, probably reflecting high packaging of protamineassociated chromatin,andanabsencefromDNAofwatermolecules. 13 Describedelsewhereinthiscatalogue www.envirogenomarkers.net www.escapeproject.eu 14 15 138 Foetalexposure: x A validated ex vivo/in vitro system for the study of transport of selected genotoxicants and immunotoxic substances across the placental barrier was establishedandapplied; x Foetal exposure assessments demonstrated from maternal/umbilical cord blood measurements in vivo benzo(a)pyrene (DNA adducts) and acrylamide haemoglobinadducts; from human placental transport studies ex vivo exposuretoallcompoundsstudiedexceptTCDD;andfromplacentaltransport modelstudiesinvitrowithBeWocellsexposuretobisphenolA,PCBsandDON. x The placental barrier does not protect against exposures to the studied compounds. Biomarkersofexposure: x x x x Three of the biomarkers were the haemoglobin adducts of acrylamide, its metaboliteglycidamideandofethyleneoxide.Thelevelsoftheseadductswere different in different countries and ethnic groups, probably reflecting differencesindietaryhabitsandfoodpreparation; Exposure to dioxin and dioxinlike chemicals, oestrogens and androgens was analysedusingdioxinreceptormediatedassays.Differencesbetweencountries wereobservedforexposurestodioxins;thereasoniscurrentlybeinganalysed; The isolated DNA samples were used for analyses of bulky DNA adducts including polycyclic aromatic hydrocarbons (PAHs). There were differences betweencountriesandwithageneraltrendtowardshigheradductlevelsinthe countriesofsouthernEurope. Most biomarkers studied showed a correlation between cord and maternal samplesandthelevelsinchildandmotherweresimilar. Biomarkersofcarcinogenicandimmunogenicrisk: x x x x Invitrogeneexpressionstudiesonhumanperipheralbloodmononuclearcells for the 12 compounds studied resulted in the identification of genes that are deregulatedbyspecificcompoundsaswellasgroupsofrelatedcompoundsand genesthatcorrelatewithmicronucleilevels; The studies revealed different transcriptomic responses to environmental carcinogens between the sexes. While exposure levels did not differ significantlybetweensexesatbirth,importantgenderspecificdifferenceswere observedingeneexpressionsassociatedwithexposure; Novel proteomic effect markers, based on expression profiles in different in vitromodelsindicativeofDONandPhIPexposurehavebeendeveloped; Childrenuptothreeyearsofage(BraMatsubcohort)wereexaminedforthe association between maternal dietary intake of dioxins, PCBs and acrylamide during pregnancy and immunerelated health outcomes. At three years there wasanassociationbetweenincreasedprenatalexposurelevelstodioxinsand PCBsthroughmother’sfoodandincreasednumbersofupperrespiratorytract infections and wheeze during the first three years of life. A reduced immune defenceagainstinfectionscouldbeamechanisticexplanation. 139 Genotypingmarkersofsusceptibility: x Two genomewide association studies have provided evidence that common germlinevariationinfluencestheriskofacutelymphocyticleukaemia. Alongsidethescientificexperimentalwork,NEWGENERIS x Setuptrainingprogrammesbothforyoungandadvancedresearchers.Over60 shortadhoctrainingortrainingcourseswereorganisedorcoorganised; x Organised over 30 scientific workshops and around 60 courses. Some will continuebeyondthelifecourseoftheproject; x Developedtrainingmediaandteachingtoolsforcourses; x Organisedover100scientificexchangevisits; x Addressedethicalaspectsrelevanttoenvironmentalepidemiologicalstudies; x Networkedwithotherongoingprojects; x Implemented a range of innovative outreach initiatives to disseminate informationandfacilitatepublicdiscussion,includingmanystakeholderevents. Coordinator: x MaastrichtUniversity,NL(Prof.JosKleinjans) Otherbeneficiaries: Organisation NationalHellenicResearchFoundation,Athens CentreforResearchonEnvironmentalEpidemiology,Barcelona UniversityofBradford UniversityofCopenhagen UniversityofLeicester KarolinskaInstitute,Huddinge FreeUniversityofBrussels GermanCancerResearchCenter,Heidelberg UniversityofOslo NationalInstituteforCancerResearch,Genoa UniversityofLeeds CatholicUniversityofLeuven NorwegianInstituteofPublicHealth,Oslo DanishEpidemiologyScienceCentre,Copenhagen UniversityofCrete,Heraklion UniversityofEasternFinland(exUniversityofKuopio) StockholmUniversity NationalInstituteofEnvironmentalHealth,Budapest InstituteforMedicalResearchandOccupationalHealth,Zagreb AutonomousUniversityofBarccelona SlovakMedicalUniversity,Bratislava BioDetectionSystemsBV,Amsterdam Imstar,Paris GenedataAG,Basel 140 Country EL ES UK DK UK SE BE DE NO IT UK BE NO DK EL FI SE HU HR ES SK NL FR CH CONTRACTNUMBER:16253 PROJECTTYPE:Integratedproject TOTALPROJECTCOST: €15052317 ECCONTRIBUTION:€13434247 STARTINGDATE:February25,2006 ENDDATE:August24,2011 DURATION:66months PHIME PUBLICHEALTHIMPACTOFLONGTERM,LOW LEVELMIXEDELEMENTEXPOSUREIN SUSCEPTIBLEPOPULATIONSTRATA Summary: 16 TheoverallaimofthePHIME integratedprojectwastoimproveassessmentofthe publichealth impact of toxic and essential metals via food, addressing the complexity of exposures, interactions (e.g., with nutrition) and risk groups (e.g., children). PHIME also addressedmechanismsforuptakeofmetalsinplantsandthus into the human food chain. Over 180 peerreviewed publications have been produced so far and many training activities, researcher exchanges and outreach activities were undertaken. The results show, inter alia, that the exposure to lead and cadmium seems to be fairly similar in many European countries, with the exception of particularly polluted areas. The exposure to lead and mercury is decreasing, while cadmiumdoesnotshowsuchafavourabletimetrend.Thetissueconcentrationsof "catalytic converter elements" platinum, palladium and rhodium are much lower than previously thought. The toxic effect of methylmercury on the central nervous systemoffoetusesandthemyocardiumofadultsismarkedlymodifiedbynutrition. Arsenicandmanganese,ingestedmainlythroughdrinkingwaterandfood,affectthe developmentandhealthoffoetuses,infantsandchildren.Leadexposureistoxicto children´s central nervous system at very low exposures. There is evidence of low levelcadmiumexposurecausingtoxicboneeffects,withadecreaseofbonemineral densityandanincreaseofosteoporosisandfractures.Preventiveactionsareneeded in light of the continuous exposure worldwide. PHIME has also increased the understanding of molecular mechanisms for the uptake of metals in plants, which will enable breeding of cereals with increased levels of essential elements, and hopefullydecreasedtoxicity. Potentialcontributiontothefollowingpolicies: x x x x Commission Regulation (EC)1881/2006 setting maximum levels for certain contaminantsinfoodstuffs CommunityStrategyConcerningMercury[COM(2005)20] EuropeanEnvironmentandHealthStrategy[COM(2003)338] Information on EU regulatory framework on heavy metals can be found at http://ec.europa.eu/food/food/chemicalsafety/contaminants/cadmium_en.htm EUfunding: x 'Foodqualityandsafety'thematicpriority 16 www.phime.org 141 Mainresults: Neurotoxicand–developmentaleffectsofheavymetals: x InFaroeIslands,acohortof490motherchildpairswasestablished,showingan exposure level lower than the four previous cohorts. Mercury (Hg) was measured in umbilical cord blood, maternal blood and hair, selenium in maternal blood, and persistent organochlorine pollutants in maternal serum. Thecohortisbeingfollowedup,andneuropsychologicalstatusisintendedto beassessedattheageof60months; x The Seychelles Child Development Studies (SCDS) investigated the effects of prenatalmethylmercury(MeHg)exposurefromfishconsumptioninearlychild and adulthood and examined the nutritional factors which may modify the effects.Psychologicaltestshavebeencarriedout.Theresultsareconfirmative ofpreviousSCDSfindings,suggestingaconfoundingroleofmaternalnutrition in studies examining associations between prenatal and postnatal MeHg exposuresanddevelopmentaloutcomes; x Neurodevelopmental outcomes were measured in 1 439 children in the Mediterranean coastal regions of Italy, Slovenia, Croatia and Greece. Overall, exposure to mercury was low and at these levels do not significantly affect neurodevelopment by the age of 18 months. Exposure to higher Hg levels duringpregnancydidnotcauselowerperformancesincognitive,languageand motor neurodevelopmental testing, since other correlated variables (e.g., socioeconomic indicators, maternal IQ) predict these outcomes. Higher fish consumption in pregnancy was associated with higher cognitive and language (butnotmotor)neurodevelopmentalperformanceat18monthsofage; x TheresultsofthestudycarriedoutinBangladeshshowedthatextensivepre and postnatal As exposure through drinking water and food resulted in increasedinfantmorbidityandmortalityandlowercognitivefunctions; x TheresultsofastudycarriedoutinFaroeIslandssuggestthatlifetimeexposure tocontaminants,i.e.,MeHgandpersistentorganicpollutants,fromtraditional foodcontributetotheincreasedincidenceofParkinson'sdisease; x Workers as well as in adolescents and elderly residents in a manganese polluted area in Italy showed preclinical deficit intremor, motor coordination andodouridentification; x AstudycarriedoutinUpperSilesiashowedthathearingfunctionwasimpaired by lowlevel lead exposure. Polymorphisms in the ALAD and VDR genes significantly modify the effects. Effects on the central nervous system, (disturbanciesofpostureandcognitivefunction),werepresentatverylowlead exposure; x In Ecuadorian gold mines, there were few toxic effects of mercury, and no significant interaction between biomarkers of exposure/risk and markers of toxicity. Cardioandcerebrovasculareffects x The results of studies conducted in Faroe Islands, northern Sweden, eastern Finland indicate that high exposure to MeHg through fish is a risk factor for myocardial infection, but the risk is modified by the simultaneous intake of 142 polyunsaturated fatty acids (PUFAs), which counteracts the methylmercury effect. Boneeffects x Studies conducted in Sweden and China provided evidence for an adverse effectoflowenvironmentalcadmiumexposureonbone(decreasedbonemass density,increasedriskofosteoporosisorfractures). Diabetesandkidneyeffects x The conclusion of Swedish studies is that an association between risk for diabetesmellitusandcadmiumexposurecanbeneitherprovennordisproven; x Doubt was cast by the results of studies carried out in Belgium, Morocco, Bangladesh,Sweden,Chinaonthecausalityofassociationsbetweenmarkersof renal tubular effects and lowlevel metals excretion. Albuminuria caused by cadmiumexposure(attheobservedexposurelevels)isareversibleeffectthat recoversaftercessationofexposure. Trendsandpublichealthimplications: x Thereisnogeneralelevatedexposuretocadmiumorleadinanyofthestudied Europeancountries,butindustrial‘hotspots’thatsignificantlyaffectchildren’s exposure can be identified in some countries, e.g., Poland, Slovakia and the CzechRepublic; x While Pb exposure has decreased, so have also the ‘safe levels’. Effects on cognitivefunctions,hearingandpostureofPbareobservedatBPb<50g/Lin blood,butthereappearstobenothreshold,implyingthattheeffectsoccurin the general population. In addition, one PHIME study suggests longterm effectsintheformofincreaseriskforkidneyfailureatthegeneralpopulation’s Pb exposure levels. Therefore, there are reasons to decrease Pb exposure further,despitethesuccessofabolishmentofPbinpetrol; x ThereisconcernforthehealtheffectofthecadmiumintakeinEuropetoday. ResultsfromPHIMEonboneeffectssuggestthatpublichealtheffectsmaybe even worse. It is, thus, worrying to note that cadmium concentrations do not showanysignofdecrease; x Forthe "catalytic converterelements"Pt,PdandRh, muchlowerlevelswere foundthanreportedearlier.Thisisbecauseofthegreatanalyticalchallengeof theseelements. Possiblesolutionsoftheproblems: x Plantsarethebasisofthefoodchainandaccumulatearangeofmetalsfrom the soil. On one hand, we would like to avoid toxic concentrations of heavy metalsinourfoodandfeedandontheotherhand,humansandotheranimals need supply of 16 minerals, including some heavy metals and transition elements,throughtheirdiet; x The uptake, transport and deposition of heavy metals in barley were addressed:barleyisarepresentativeofthesmallgrainedcerealsthatcomprise themajorfoodsourceforhumans,andisacloserelativeofwheat.Additionally, the most promising genes were introduced into tomato and tobacco, representativesoffruitandleafcrops; 143 x By integrating state of the art technologies in plant physiology, molecular biology and genetics, certain plant genes were identified, characterised and manipulated. The genes of concern were those involved in (i) avoidance of harmfulmetalsor(ii)inclusionofmetalsofnutritionalconcerninthegrainand inleaves.ThefocuswasonCd,Hg,ZnandMn. Coordinator: x LundUniversity,SE(Prof.StaffanSkerfving) Otherbeneficiaries Organisation JožefStefanInstitute,Ljubljana InstituteofChildHealth,Athens KarolinskaInstitute,Stockholm UmeåUniversity InstituteofBiomedicalResearch,KaunasUniversityofMedicine CatholicUniversityofLouvain,Brussels MinistryofHealth,Victoria,Seychelles NationalInstituteofPublicHealth,Prague UlsterUniversity,Coleraine OikonLtd.,Zagreb OyJurilabLtd.,Kuopio RegionalAuthorityofPublicHealthBanskáBystrica FaroeseHospitalSystem,Tórshavn InternationalCentreforDiarrhoealDiseaseResearch,Dhaka UniversityofUdine UniversityMedicalCentre,Ljubljana UniversityofBrescia FudanUniversity,Shanghai UniversityofSouthernDenmark,Odense InstituteofOccupationalMedicineandEnvironmentalHealth, Sosnowiec RoyalVeterinaryandAgriculturalUniversity(KVL),Frederiksberg ResearchCentreFlakkebjerg,Slagelse LeibnizInstituteofPlantBiochemistry,Halle UniversityofSouthampton UniversityofZürich MaxPlanckInstituteofMolecularPlantPhysiology,Potsdam UniversityofYork InstituteforEcologyofIndustrialAreas(IETU),Katowice UniversityofWarsaw UniversityofRochester 144 Country SI EL SE SE LT BE SC CZ UK HR FI SI DK BD IT SI IT CN DK PL DK DK DE UK CH DE UK PL PL US CONTRACTNUMBER:513991 PROJECTTYPE:Specific targetedresearchproject TOTALPROJECTCOST: €3150000 ECCONTRIBUTION:€3000000 STARTINGDATE: March1,2005 ENDDATE:February28,2008 DURATION:36months PIONEER PUBERTYONSETINFLUENCEOF ENVIRONMENTALANDENDOGENOUS REGULATORS Summary: 17 ThemaingoalofPIONEER wastoimprovethe understanding of precocious puberty, its occurrence in Europe, and the role of nutrition and specific food components in the regulation of reproductive maturation. A significantamountofnewdatawasobtainedontheseaspects.Theoverallearlyage at the onset of puberty and the increased incidence of sexual precocity in foreign children, who migrate from developing countries to Western Europe or to USA, further emphasize the role of nutritional and environmental factors in the timing of puberty. There is also a need for studies assessing the timing and dynamics of pubertal development in association with the nutritional status in developing countries. Through the work conducted by the PIONEER consortium partner in Pakistan, collection of data on the pubertal development and the nutritional status of Pakistani children was initiated, giving important and novel information on the situation in a less developed country. Information generated in PIONEER could be used to identify the individuals or groups at high risk, and to design specific actions to prevent premature reproductive maturation and its long term adverse consequences. However, considering the complexity of genetic and environmentalfactorsthatregulatepubertyonset,asdemonstratedinPIONEER,no simplerecommendationsforpreventivestrategiescanyetbegiven. Potentialcontributiontothefollowingpolicies: x EuropeanEnvironmentandHealthStrategy[COM(2003)338] x CommunityStrategyforEndocrineDisruptersCOM(1999)706final; x A Strategy for Europe on Nutrition, Overweight and Obesity related health issues[COM(2007)279final] EUfunding: x 'Foodqualityandsafety'thematicpriority 17 http://cascade.projectcoordinator.net/~pioneer 145 Mainresults: x Theclinicalandexperimentalstudiesconfirmedthatthegeneticbackgroundis astrongdeterminantforthetimingofpubertyonset,andnewinformationon thegeneloci,genesandthedownstreameffectsassociatedwiththetimingof pubertyinhumanswasobtained; x The data set obtained in PIONEER allows modelling of pubertal development data and gives more complete information about longitudinal changes on pubertaldevelopmentanddifferencesbetweensexes; x It is not likely that changes in dietary habits could override the strongest genetic impacts, but, on the other hand, PIONEER studies show that factors that are regulated by both nutrition and the genetic background (e.g., body weight)haveastrongeffectonthetimingofpuberty; x Novelmechanisticinformationwasobtainedonthefactorsandpathwaysthat areinvolvedintheonsetofpubertyandsexualmaturation; x Novelmodellingapproachesweredeveloped(e.g.,geneticallymodifiedmouse linesandsetsofbiomarkers)thatcanbeusedfortheinvestigationofpuberty andsexualmaturationinexperimentalconditions.Thesemodelswereusedto investigate the effects and mechanisms of nutritional interventions and selecteddietderivedendocrinemodulators; x The impact of environmental factors influencing puberty onset cannot be consideredinisolationfromendogenousfactors; x With a multidisciplinary and translational approach, PIONEER has and will facilitate the identification of highrisk groups and the development of novel experimentaltestmodelsneededforthedevelopmentofpreventivestrategies; x Several scientific papers, describing results obtained in PIONEER, have been publishedinhighimpactscientificjournals. Coordinator: x UniversityofTurku,Turku,FI(Prof.SariMäkelä) Otherbeneficiaries: Organisation KarolinskaInstitute,Stockholm/Huddinge UniversityofRome'LaSapienza' NationalCentreforScientificResearch(CNRS),Paris KuopioUniversityHospital UniversityofHelsinki SemmelweissUniversity,Budapest ImperialCollegeofScience,TechnologyAndMedicine, London UniversityofLeipzig CharitéUniversityMedicalCenter,Berlin TheAgaKhanUniversity,Karachi 146 Country SE IT FR FI FI HU UK DE DE PK CHAPTERIIIProjectsFocusedontheDevelopmentofMethodsandToolsforEnvironmentandHealthRiskandImpactAssessment CHAPTERIII Projectsfocusedonthe developmentofmethodsand toolsforenvironmentandhealth riskandimpactassessment 147 148 CONTRACTNUMBER:22936 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€1087510 ECCONTRIBUTION:€633550 STARTINGDATE:April1,2006 ENDDATE:September30,2009 DURATION:42months BENERIS BENEFITRISKASSESSMENTFORFOOD: ANITERATIVEVALUEOFINFORMATION APPROACH Summary: 1 ThegeneralobjectiveofBENERIS wasto create a framework for handling complicatedbenefitrisksituations,andapplyitfortheanalysisofthebenefitsand risksofcertainfoods.Thefirstfoodcommoditytobeusedinthedevelopmentofthe methodologywasfish.Onespecificobjectivewastodevelopimprovedmethodsfor doseresponseassessment,combiningepidemiologicalandtoxicologicaldata,andto apply them in combining epidemiological and toxicological information on fish contaminants (especially dioxins and polychlorinated biphenyls [PCBs]). The main outcomesofBENERISare(i)improvedmethodology(openassessment)forbenefit risk assessments; (ii) the web workspace Opasnet for performing them in a collaborative way; (iii) and the Opasnet Base database containing readytouse information needed in assessments. Interested assessors have been identified and contacted for workingwiththeirownassessmentsusingthewebsite. These practical reallife examples will be a major method for disseminating the results of BENERIS. BENERIS formed a cluster with another project issued from the same call, namely QALIBRA(describedelsewhereinthispublication). Potentialcontributiontothefollowingpolicies: x EuropeanEnvironmentandHealthStrategy[COM(2003)338] x CommunityStrategyforEndocrineDisruptersCOM(1999)706final x Council Regulation (EEC)315/93 laying down Community procedures for contaminantsinfood;CommissionRegulation(EC)1881/2006settingmaximum levelsforcertaincontaminantsinfoodstuffs. EUfunding: x 'Foodqualityandsafety'thematicpriority 1 www.qalibrabeneris.eu 149 Mainresults: x Anewbenefitriskassessmentmethod(openassessment)hasbeendescribed on the web workspace Opasnet (http://en.opasnet.org). This work has continuedaftertheprojecthasended; x Opasnet is a website to collect, organise and distribute information on issues relevantforbenefitriskanalysesoffood.Italsocontainsmaterialaboutmany othertopicsthanfood,e.g.,climatechangepoliciesandhealth,healthrisksof airpollution,andemissionsofmetalindustry.Thestatisticsofuseattheendof 2009wasasfollows:Therewere980webpages,450files,176users,and270 000 page views. The contents are open and freely available to all. Several assessments are being worked on at the website. Interested parties are welcometocontributetothecasestudieswiththeirowninformation,aslong asitisofferedunderapropercopyright; x TheBENERISfishcasestudywasdescribedinOpasnetintwoparts:aseparate subassessment was performed on methylmercury and omega3 fatty acids in children, and the full assessment included also other pollutants and health endpoints; x SeveralassessmentcasestudiesareunderwayoutsideBENERIS.Thewebsiteis designed for assessments that are performed openly, allowing also for stakeholderparticipation.AdatabasecalledOpasnetBasewasusedtoupload modelresultsandnutritionstudiesperformedinBENERIS. Coordinator: x NationalInstituteforHealthandWelfare,Kuopio,FI(Dr.JouniTuomisto) Otherbeneficiaries: Organisation Country DelftUniversityofTechnology NL OyFoodfilesLtd,Kuopio FI FoodSafetyAuthorityofIreland,Dublin IE TechnicalUniversityofDenmark,KongensLyngby DK DanishVeterinaryandFoodAdministration,Søborg DK LendacDataSystemsLtd,Dublin IE FundaciónPrivadaparalaInvestigaciónNutricional, ES Barcelona 150 CONTRACTNUMBER:22788 PROJECTTYPE: Specifictargetedresearch project TOTALPROJECTCOST: €1252710 ECCONTRIBUTION:€800000 STARTINGDATE: November1,2005 ENDDATE:January31,2008 DURATION:27months DROPS DEVELOPMENTOFMACROANDSECTORALECONOMIC MODELSAIMINGTOEVALUATETHEROLEOFPUBLIC HEALTHEXTERNALITIESONSOCIETY Summary: 2 The overall objective of DROPS was to provide a full chainanalysisrelatedtotheimpactofhealthprotection measures related to priority pollutants as identified by the European Environment andHealthActionPlan.Theprojectaimedatextendingexistingmethodologiesand models to provide an impact pathwaybased model for evaluationoftheroleofpublichealthexternalitiesonsociety, made operational for the selected pollutants [ozone, heavy metals (mercury, cadmium, arsenic, nickel, lead), polychlorinated biphenyls [PCBs], dioxins and indoor air pollution]. Emission inventories have been collected for years 2000 and for two different scenarios (business as usual + climatechange,maximumfeasibletechnicalreduction)for2010and2020,forheavy metals, PCBs and dioxins. For PCBs and dioxins, this is the first time that such emissionscenarioswereconstructed,andtheyareasubjectofdiscussionsbetween emission experts in various European countries and their users within the United Nations Convention on Longrange Transboundary Air Pollution Convention. The estimates of emissions and emission scenarios will be used in negotiations of emission reductions on European level. A database of health endpoints has been compiled including health endpoints relevant to heavy metals, PCBs and dioxins. A valuation of health impacts from societal perspective was carried out. A review of doseresponse functions and concentrationresponse functions for the impact of ozoneoncropswasperformed.Theintegratedassessmentmodellingsystemusedby theUniversityofStuttgartwasenhanced.TheE3MEmodel,alargescaleeconomic model based on the system of national accounts, was expanded to include seven additional emission types, which were linked to economic and energy demands within the existing modelling framework. Detailed results are available at http://cordis.europa.eu/search(useDROPSassearchword). Potentialcontributiontothefollowingpolicies: x x x x EuropeanEnvironmentandHealthStrategy[COM(2003)338] ThematicStrategyonAirPollution[COM(2005)446] CommunityStrategyConcerningMercury[SEC(2005)101] ConventiononLongrangeTransboundaryAirPollution EUfunding: x 'Scientificsupporttopolicy'thematicpriority 2 http://drops.nilu.no 151 Mainresults: x Emissioninventoriesfortheyear2000,forselectedpersistentorganicpollutants (POPs)andheavymetals:Emissioninventorieshavebeencollectedfortheyear 2000formercury,cadmium,arsenic,nickel,lead,PCBsanddioxins.Theinput data has been extensively verified and compared to existing emission inventories(EPER,CORINAIR).Differenceshavebeendiscussedandexplained. The emission inventories have already contributed to the work of the United Nations Economic Commission for Europe (UNECE) Convention on Longrange TransboundaryAirPollutionConvention(LRTAP)andcanbeusedforresearch and assessment. The results are available in a database, subject to revisions basedonfurtherresearchandconsultations; x Emission scenarios for the years 2010 and 2020 for two different scenarios (bysiness as usual [BAU] + climate, maximum feasible technical reduction [MFTR]) for heavy metals, PCBs and dioxins: Emission scenarios have been collected for year 2010 and 2020 for mercury, cadmium, arsenic, nickel, lead, PCBs and dioxins. The results are available as a database, subject to revisions pendingfurtherresearch; x Identificationandeconomicassessmentofpotentialhealthbenefits:Adatabase of concentrationresponse functions for particulate matter (PM), selected heavy metals (HM), dioxins and PCBs has been developed. A review of monetaryvaluationresultsforthesamehealthendpointshasbeencarriedout; x Identificationandeconomicassessmentofbenefitstocropsfromreductionsin ozone in Europe: A database and maps of expected changes in damage to wheat, potatoes, grapes, tomatoes, and apples, based on the ozone concentrations as predicted by the Clean Air for Europe (CAFÉ) initiative and theUNECE,areavailable; x Evaluationofimpactontotalairexposureandinhalationofmeasurestoreduce PM: Results of a modelling exercise are available, providing an individual assessment of (inhalationrelated)exposures and inhaled doses for PM for 24 hours, based on outdoor concentrations of PM in two fractions on urban backgroundandtrafficsitesfromHalle(DE),Krakow(PL)andTrondheim(NO), smokingandopenfireplaceuseindoors,andindividualtimeactivitypatterns. Thestudydemonstrateshowtheindividualexposurefactors(gender,activity, time spent in different microenvironments, smoking) influence exposure and inhaled dose, and to what extent indoor concentrations are modified by time spentindoors,givenuniformpredefinedcharacteristicsofthebuilding.Thiscan be used for the assessment of measures to reduce PM, both in relation to concentrationchangesandtochangesinsizedistributionprofile; x Enhancement of an integrated assessment model: An integrated assessment model has been improved, allowing the assessment of heavy metals and selected POPs, covering emissions, transport and fate of pollutants, their effects taking into account exposures through inhalation and ingestion, and monetaryvaluationsoftheseeffects,onnationalandEuropeanlevel.Different discountingoptionsandvaryingtimehorizonsareconsidered.Casestudiesfor Poland,Norway,GermanyandtheCzechRepublicareavailable. 152 x Enhanced macroeconomic model E3ME: The 'EnergyEnvironmentEconomy ModelofEurope'(E3ME)hasbeenmodifiedtobecompatiblewithUNECEused emissionscenarios,emissionrelatedactivityinformationandotherinformation oneconomicandtechnologicalsectors.Themodelhasbeenextendedtocover heavymetalsandPOPs. Coordinator: x NorwegianInstituteforAirResearch(NILU),Kjeller,NO(Dr.JozefPacyna) Otherbeneficiaries: Organisation Country UniversityofStuttgart DE CharlesUniversity,Prague CZ InstituteforEcologyofIndustrialAreas(IETU),Katowice PL MedicalUniversityofSilesia,Katowice PL NILUPolskaLtd.,Katowice PL CambridgeEconometricsLimited UK 153 154 CONTRACTNUMBER:44232 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€1050845 ECCONTRIBUTION:€900000 STARTINGDATE:March1,2007 ENDDATE:February28,2009 DURATION:24months ENVIRISK ASSESSINGTHERISKSOF ENVIRONMENTALSTRESSORS: CONTRIBUTIONTOTHEDEVELOPMENT OFINTEGRATINGMETHODOLOGY Summary: The relevant call for proposals from whichENVIRISKwasselectedaskedfortheexploitationofrecentorcurrentresearch findingsandprojectresultsforthesupportofidentifiedEuropeanpolicies.Thegoals 3 ofENVIRISK werethereforeformulatedinagreementwiththeproposedobjectives of the task 'Assessing the risks of environmental stressors'. ENVIRISK has reviewed researchoftwogroupssystematicallystudyingenvironmentalhealtheffectsover20 years.Basedonthis,theprojectdevelopedanintegratedmethodologicalframework toidentifyhealthriskscausedbyexposurestoenvironmentalfactors,withaviewto provide for quantitative assessment and comparison of the benefits of alternative prevention and targeted policy measures against their respective costs. Specific aims included the assessment of existing information on exposure and health effects, the establishment of links between exposure and health including framework and protocol development, and the contribution to the European Integrated Environment and Health Information System(EHIS).However,assuchasystemwasnotinpreparationduringtheproject lifetime,theplanonthissetoftaskswasrevisedandresourcesredirected. Potentialcontributiontothefollowingpolicies: x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Scientificsupporttopolicy'thematicpriority 3 http://envirisk.nilu.no 155 Mainresults: x ENVIRISKdevelopedandappliedamodelforinfantexposuretopolychlorinated biphenyls (PCBs) through diet, for adult exposure to PCBs from diet, and a framework for exposure assessment related to polycyclic aromatic hydrocarbons (PAHs). The consortium assessed the costs of protocol implementation that would be required to implement monitoring on these issues.Ittriedseveralmethodsforinterpolationofambientconcentrationsof pollutantsbasedonmonitoringdatasources,andperformedareviewonPAH sourcesandconcentrationsonEuropeanlevel; x Regarding evaluation of health effects, the consortium reviewed and summarised research in two major reports. It also used these results for risk assessment. Being informed by this work, the project has developed an environmentalhealthsurveythatstartedin2009andwhichwilldocumentthe effectsofPAHsonhumanhealthinahotspotpollutionlocation(Ostrava,CZ). Thiswillinformthefuturedevelopmentofrequirementsforanenvironmental healthinformationplatform; x The consortium further developed a tool that can be included in a environmentalhealthinformationsystem,theexpoplatform; x Areviewwascarriedoutondoseresponsefunctionsrelevanttoendpointsin thisproject.Inaddition,abenchmarkdoseapproachwasfurtherdeveloped; x To advance work on defining needs for exposure assessment, two existing databases containing environmental, biomarker and health information were sharedwithintheconsortium,andworkhasadvancedonestimatingindividual exposuresbasedontheavailabledata; x Inordertoextrapolateinformationtoalargergeographicalscale,astudywas performedonsources,sourcesignaturesandlevelsofPAHsinEurope; x Theprojectcoorganisedworkshoponbiomarkersinhealthimpactassessment, andliaisedwithotherresearchprojects; x BasedonthefindingsandworkdoneinENVIRISK,theconsortiumsuggesteda list of factors that should be included into an integrated methodological framework for identification of health risks caused by exposures to environmentalfactors. Coordinator: x NorwegianInstituteforAirResearch(NILU),Kjeller,NO(Dr.AlenaBartonova) Otherbeneficiaries: Organisation NationalInstituteforHealthandWelfare(THL),Helsinki, Kuopio InstituteofExperimentalMedicine,Prague UniversityofHertfordshire,Hatfield SlovakMedicalUniversity,Bratislava TechnionIsraelInstituteofTechnology,Haifa 156 Country FI CZ UK SK IL CONTRACTNUMBER:502527 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST: €1433056 ECCONTRIBUTION:€892078 STARTINGDATE:January1,2004 ENDDATE:March31,2007 DURATION:39months ESPREME ESTIMATIONOFWILLINGNESSTOPAYTO REDUCERISKSOFEXPOSURETOHEAVYMETALS ANDCOSTBENEFITANALYSISFORREDUCING HEAVYMETALSOCCURENCEINEUROPE Summary: The aim of ESPREME was to develop methods andstrategiestosupportEUenvironmentalpolicymakingforreducingtheemissions andthustheharmfulimpactsofheavymetals.Theprojectcame,interalia,tothe following conclusions: (i) Progress has been made in estimating emissions of heavy metals to the atmosphere at a country and regional (European) level; (ii) Emission estimates prepared by ESPREME are higher than the estimates previously provided by countries within the EuropeanMonitoringandEvaluationProgramme(EMEP); (iii)Alistof48individualprocesses(activities)responsible for heavy metal emission was the base for the selection of abatement options of heavy metals emission to the air; (iv) 483 emission abatement measures have been analysed; (v) The emission abatement measures database contains information on each individual control method as well as combinationsofthemethods;(vi)Pb,AsandHgcausehigheroverallhealthimpacts and,thus,relatedcoststhanCd,Cr(VI)andNi;(vii)Undiscountedmarginalexternal costsperkgreleasedrangefromseveral€[NiandCr(VI)],aboutseveralten€(Cd), severalhundred€(AsandPb)toseveralthousand€(Hg);(viii)Agriculturalactivities cause the highest (long term) human health damage for Cr, Ni, Pb, Cd and possess the highest reduction potential; (ix) Combustion of fuels in stationary sources, especially for cement production, iron and steel manufacturing, and nonferrous metal production, is still the main source of ESPREME heavy metals, except for Pb (gasolinecombustion);(x)Moreextensiveintroductionofrenewableenergysources may result in reducing the coal combustion and thus heavy metal emissions. More 4 detailscanbefoundontheprojectwebsite . Potentialcontributiontothefollowingpolicies: x x x x x Thematicstrategyonairpollution[COM(2005)446] Directive 2001/81/EC on national emission ceilings for certain atmospheric pollutants Conventiononlongrangetransboundaryairpollution Communitystrategyconcerningmercury UnitedNationsEconomicCommissionforEurope(UNECE)Aarhusprotocolon heavymetals EUfunding: x 4 'Scientificsupporttopolicies'programme http://espreme.ier.unistuttgart.de 157 Mainresults: x Europeanwideemissiondataoftheheavymetalswasprovided,improvedand consolidated; x Systematic collection of data was carried out on possibilities to reduce emissions. Data on costs and effectiveness of abatement options have been collected as well as stock and activity data and emission factors for 2000 and 2010; x Improvement of models was undertaken for the transport of heavy metals in air, soil and water and their application to simulate the transport of heavy metals in these media. Modelling results vs. measurement data have been evaluated; x Collectionofinformationonexposureresponserelationshipsforhumanhealth aswellasonthresholdsfordamagestoecosystemswascarriedout; x Assessment of avoided damage from heavy metal exposure by transferring monetaryvaluesfromavailablecontingentvaluationstudieswasconducted; x Estimation of the health impacts and of the exceedances of critical loads for ecosystems for two scenarios for 2010 was obtained: a business as usual scenario (BAU), and a maximum feasible technical reduction (MFTR) scenario where a number of economically feasible technical measures have been implemented,inadditiontothosealreadyimplementedintheBAUscenario; x Estimationofoveralldamagecostspercountryandofcountryspecificcostsper tonneofheavymetalsreleasedwascarriedout. Coordinator: x UniversityofStuttgart,DE(Prof.RainerFriedrich) Otherbeneficiaries: Organisation NorwegianInstituteforAirResearch(NILU),Kjeller InstituteforEcologyofIndustrialAreas(IETU),Katowice SwedishEnvironmentalResearchInstitute,Stockholm InstituteofOccupationalMedicine,Edinburgh MeteorologicalSynthesizingCentreEast,Moscow InstituteforAtmosphericPollutionResearch,Rende CzechHydrometeorologicalInstitute,Prague EtzelMüszakiSzolgáltatóBt.(EtzelEngineeringService), Budapest NILUPolskaLtd.,Katowice 158 Country NO PL SE UK RU IT CZ HU PL CONTRACTNUMBER:36976 PROJECTTYPE:Integratedproject TOTALPROJECTCOST: €2581000 ECCONTRIBUTION:€1630000 STARTINGDATE: February2,2007 ENDDATE:January31,2011 DURATION:48months 2FUN FULLCHAINANDUNCERTAINTY APPROACHESFORASSESSING HEALTHRISKSINFUTUREENVIRONMENTAL SCENARIOS Summary: Theprimaryaimof2FUNwastodevelopintegratedmethodsandriskanalysistools to help the decisionmakers to define their priorities in environmental health management.Asitwasnotpossibletobuildanentireintegratedframework,2FUN therefore focused on the: (i) construction of longterm environmental and socio economic scenarios at the regional scale; (ii) integration of multimedia transport modelswithpredictivechemistryandhumanexposuremodels;(iii)advancementof thestateofscienceoftoxicitypredictionformixturesofsubstances;(iv)accounting for children populations in health risk assessments; (v) development of new and improved tools for uncertainty analysis. The tools developed were tested in three casesstudies covering a wide range of environmental, temporal, spatial, sectoral and social problems in three regions of Europe: (i) evolution of air pollution, consequences of climate change and emissions of air pollutants in Portugal; (ii) choices of industrial technologies to minimize the impact of the industrial and agricultural activities on population health at the level of a river watershedinFrance;(iii)healthriskassessmentforchildrenintheindustrialareaof Upper Silesia in Poland. The tools developed are freely available on the project 5 website .TheywillultimatelybeincludedintheHEIMTSAtoolbox(projectdescribed elsewhereinthiscatalogue). Potentialcontributiontothefollowingpolicies: x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 5 www.2fun.org 159 Mainresults: x Amethodologyandcasestudydataforidentificationandrankingofriskfactors wasdeveloped; x Methodologies for downscaling global socioeconomic, technological, meteorologicalandemissionscenariostoregionallevelsweredeveloped.They werevalidatedagainstdataforPortugal; x AnimplementationinR(www.rproject.org)ofgnosticmethodsforrobustdata treatmentanduncertaintyanalysiswasundertaken; x Multimediatransportanddispersionmodelsandsoftwarewereimproved; x A critical review of exposure pathways and parameters relevant for children wascarriedout; x A generic physiologically based pharmacokinetic (internal dose) model for humans, coupled seamlessly with the above multimedia models, was developed; x Specific quantitative structureproperty relationships (QSPR) models for predicting physiologically based pharmacokinetic (PBPK) model parameters weredeveloped; x Methods and software for automated metabolic interactions modelling were designed; x A coupling of PBPK and doseresponse models for risk assessment based on toxicitydatawasattempted; x Databaseswerecreatedandcasestudiesdevelopedtodemonstratetheuseof someoftheabovemodelsandmethods; x Joint use, training and dissemination activities were organised with INTARESE andHEIMTSA(projectsdescribedelsewhereinthiscatalogue); x Disseminationactivitieswereundertaken:e.g.,projectleafletsweredistributed in numerous meetings; eight newsletters and a finalbrochure were produced and distributed; 21 scientific articles published (a few more have been submitted),39posterspresentedand52oralcommunicationsgiven; x SevenPhDstudentsandnumerousmaster'sstudentsweretrained. 160 Coordinator: x French National Institute for Industrial Environment and Risks (INERIS), VerneuilenHalatte,FR(Prof.FrédéricBois) Otherbeneficiaries: Organisation Country ElectricitédeFrance(EDF),Chatou FR EuropeanCommission,JointResearchCentre(JRC),Ispra IT HelmholtzCentreforEnvironmentalResearch,Leipzig DE TechnicalUniversityofDenmark,KongensLyngby DK FaciliaAB,Bromma SE InstituteforEcologyofIndustrialAreas(IETU),Katowice PL OstravaInstituteofPublicHealth CZ PT UniversityofLisbon,FacultyofSciences CatholicUniversityoftheSacredHeart,Milan IT UniversityofCa’Foscari,Venice IT FlemishInstituteforTechnologicalResearch(VITO),Mol BE 161 162 CONTRACTNUMBER:36913 PROJECTTYPE:Integratedproject TOTALPROJECTCOST: €7138904 €ECCONTRIBUTION:€4999780 STARTINGDATE: February1,2007 ENDDATE:January31,2011 DURATION:48months HEIMTSA HEALTHANDENVIRONMENTINTEGRATED METHODOLOGYANDTOOLBOXFORSCENARIO ASSESSMENT Summary: 6 ThemainobjectivesofHEIMTSA wereto:(i)Develop andprovideimprovedmethodsforhealthimpactassessment(HIA)andcostbenefit analysis (CBA) of environment and health issues, as reliably as practicable given current knowledge. This means using the best uptodate scientific knowledge, especiallyonissuesthathaveabiginfluenceonfinalanswers; (ii) Develop an associated set of tools: a modular integrated assessment system (IAS) for implementing the methodology Europewide; (iii) Apply the methods and tools to selected realisticpolicyscenariosattheEuropeanlevel.Theseincludebaselinescenarios,and alternative scenarios developed with the aid of policymakers and other potential endusers; (iv) Contribute to developing HIA/CBA capability in Europe, through its improvementsinmethodsandtools,throughdisseminationandtraining,andmore generally, through raising the profile of HIA/CBA methods, and by showing what is possible. HEIMTSA and INTARESE (described elsewhere in this catalogue) have together developed a general methodology of integrated environmental health impactassessment(IEHIA),fromemissionsthroughtohealthimpacts,aggregatedvia DisabilityAdjustedLifeYears(DALYs)and/orviamonetaryvaluesandincorporating human health risk assessment as an integral component. The two projects have elaborated that methodology by developing and working through the fullchain approach for many pollutants and have demonstrated its application to the environmentalhealthimpactassessmentofpoliciesinseveralsectors,includingthe complex set of policies and measures to address climate change. The IEHIA methodology developed and proposed has been related to other approaches to environmental HIA, e.g., the (modified) DPSEEA (Drivingforcespressuresstate exposureeffectaction) framework of WHO. This provides a significant progress beyondthestateoftheartwhentheprojectbegan. Potentialcontributiontothefollowingpolicies: x x x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EuropeanEnvironment&HealthActionPlan20042010"[COM(2004)416] ManysectoralEUpolicies(climate,airpollution,noiseetc) EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 6 www.heimtsa.eu 163 Mainresults: x Methods: HEIMTSA has helped clarify the overall methodology of integrated environmentalhealthimpactassessmentandextendeditsrangeofapplication by making numerous detailed contributions to methods and good practice in termsof(i)generalissueswithineachstageofthefullchain;(ii)generalissues of linkage across stages of the full chain; (iii) specific issues for particular pollutantsorhealthendpoints,withinparticularstagesofthefullchain;and(iv) fullchainanalysesofseveralpollutants(theHEIMTSAcasestudies); x Examples/case studies: Working jointly with INTARESE, HEIMTSA has shown how the general methodology and many of the specific methods developed during the project can be applied to a complex suite of policies affecting the environmentandenvironmentalexposuresinnumeroussectorsandviaalarge numberofpollutantsandresultanthealthoutcomes; x Tools: (i) HEIMTSA has contributed to the guidance system and toolkit, conceived and designed by INTARESE; (ii) HEIMTSA has developed some particular tools, including ones for the qualitative assessment of uncertainty andforvisualisation,andhasincorporatedthesealongwithmanypreexisting modelsandothernewinformationintoacomputationalsystemforintegrated environmentalHIA.Thoughnotyetfullydeveloped,itformsthebasisforfuture applications; (iii) The project also developed a ‘light’ version of the computational system for training and learning purposes and other explorationsofthefullchain; x Capacitybuilding:HEIMTSAhashelpedtogrowandstrengthenthecommunity of practitioners and users of integrated environmental HIA; and this will continue beyond the life of the project, as dissemination continues and as relationshipsmadeandknowledgegainedareusedinnewcontexts.Thelegacy ofHEIMTSAandINTARESEwillbesubstantiallybetterifthemethodsandtools willbefurtherdeveloped,andexperiencecollatedfromapplyingthem; x SomeoftheworkiscontinuinginaprojectfundedbytheSeventhFramework ProgrammecalledURGENCHE(Greenhousegasemissionreductionpoliciesand theirimpactsonpublichealthandwellbeinginurbanareas). 164 Coordinator: x InstituteofOccupationalMedicine,Edinburgh,UK(Dr.FintanHurley) Otherbeneficiaries: Organisation Country UniversityofStuttgart DE NorwegianInstituteforAirResearch(NILU),Kjeller NO UniversityofBath UK ImperialCollegeofScience,TechnologyAndMedicine, UK London FlemishInstituteforTechnologicalResearch(VITO),Mol BE InstituteofAppliedScientificResearch(TNO),Utrecht, NL Zeist,Leiden NILUPolskaLtd.,Katowice PL NorwegianMeteorologicalInstitute,Oslo NO IT EuropeanCommission,JointResearchCentre(JRC),Ispra CzechHydrometeorologicalInstitute,Prague CZ SwissFederalInstituteofTechnology,Zürich CH MeteorologicalSynthesizingCentreEast,Moscow RU AssociationforTechnologyandStructuresinAgriculture DE (KTBL),Darmstadt TechnicalUniversityofDenmark,KongensLyngby DK FR ÉcoledesPontsParisTech,ChampssurMarne UtrechtUniversity NL CharlesUniversity,Prague CZ SwecoGrønerAs,Oslo NO SlovakMedicalUniversity,Bratislava SK NationalInstituteforHealthandWelfare(THL),Kuopio FI UniversityofMünster DE UniversityofExeter UK 165 166 CONTRACTNUMBER:18385 PROJECTTYPE:Integratedproject TOTALPROJECTCOST: €17341697 ECCONTRIBUTION:€12379832 STARTINGDATE:November1, 2005 ENDDATE:January31,2011 DURATION:63months INTARESE INTEGRATEDASSESSMENTOF HEALTHRISKSFROMENVIRONMENTAL STRESSORSINEUROPE Summary: 7 The overall goal of INTARESE was to: (i) devise both a conceptual and analytical framework for integrated environmental health impact assessment (IEHIA), based on the impact pathway; (ii) develop, test anddemonstratethemethodsandtoolsneededtocarryoutIEHIA;(iii)illustratethe useofIEHIAthroughaseriesofcasestudies,focusingonissuesofpolicyconcernin the EU (sectors: transport, housing, agriculture, water, wastes, household chemicals and climate); and (iv) create a computerbased ‘toolbox’, which captured all these developments (the concepts, methodsandcasestudies)andprovidedbothalongtermlegacyfortheprojectand a practical means by which users in future could access relevant information and tools.Workduringthefirstfouryearsoftheprojectconcentratedondevelopingthe underlying principles for integrated assessment, developing the methods required forintegratedassessment,testingandtriallingthesethroughaseriesofcasestudies, anddesigningandbuildingatoolboxforintegratedassessment,tobedevelopedin laterstagesoftheproject.Inthefinalyearoftheproject,thefocuswasonfinalising themethodologicalworkandcasestudiescarriedoutinpreviousyears;conductinga large, complex case study on integrated environmental health impact assessment (thesocalledCommonCaseStudyfocusedonclimatechangeandpolicies,donein collaborationwithHEIMTSA[describedelsewhereinthiscatalogue]);andintegrating all the key results of the project into the toolbox (the Integrated Environmental HealthImpactAssessmentSystem). Potentialcontributiontothefollowingpolicies: x x x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EuropeanEnvironment&HealthActionPlan20042010"[COM(2004)416] ManysectoralEUpolicies(climate,airpollution,noiseetc) EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 7 www.intarese.org 167 Mainresults: Bytheendoftheproject: x The concept of integrated environmental health impact assessment has been developed, spelled out in a number of publications, and already incorporated intootherEUprojects,e.g.,URGENCHE; x The methodology of integrated environmental health impact assessment has beenworkedoutintheformofaclearanalyticalprocedure,whichprovidesthe frameworkforalltheotheroutputsandresults; x The detailed methods and tools needed at each stage in the process of integrated environmental health impact assessment (issueframing, design, execution and appraisal) have been identified, evaluated, tested and, where appropriate, developed from scratch, and described in the form of protocols andguidancemanuals; x Detailedreviewsandevaluationshavebeencarriedoutofthedataneededto supportthesemethods; x Routine use of integrated environmental health impact assessment, covering environmental, biomonitoring and other (e.g., demographic, health) data sets andstrategiesfordevisingmoreintegratedapproachestomonitoringhasbeen supported; x An extensive series of case studies has been completed, covering individual methods(e.g.,estimationofexposureresponsefunctions,uncertaintyanalysis, expertelicitation),assessmentofindividualcausalpathwaysorsectors(relating totransport,housing,agriculturallanduse,drinkingwaterquality,chemicalsin householdarticlesandproducts,wastemanagement,andclimatechange),and (in collaboration with the HEIMTSA project) a full integrated assessment of a major policy area in the EU (health impacts of climate change mitigation and adaptationpolicies); x All these materials and outputs have been brought together in a large and comprehensiveonlineIEHIAsystem,whichprovidesseveralhundredpagesof guidance on how to devise and carry out assessments, access to and evaluations of key data sources, descriptions and downloadable copies of a wide range of models and methods, an extensive library of detailed worked examples and case studies, and gateways to external platforms for open and integratedassessmentdevelopedaspartofrelatedprojects.Thisisavailableat http://www.integratedassessment.eu; x Closecollaborationwithuserswascarriedoutthroughouttheproject,bothvia a Project Advisory Group and purposedesigned consultation events, and a wide range of dissemination and training materials (over and above the toolbox) have been produced, including a series of Technical Briefs, project workshops,presentationsatinternationalconferencesandpublishedpapersin peerreviewedjournals; 168 x x x x Closecollaborationwasalsodevelopedand maintainedwitharangeofother EUfunded projects, both formally (e.g., via organisation of joint meetings, attendanceatplanningmeetings,exchangeofprotocols),andinformally(e.g., viasharedstaff,technicaldiscussions).Amongstthese,thestrongestandmost productive collaboration was with HEIMTSA, and included joint working on a numberofactivitiesanddeliverables,regularconsultationbetweentheproject coordinators,andarangeofjointplanningandtechnicalmeetings.; Attheendoftheproject,INTARESEhadproduced33publishedpapers;8were inthereviewandpublicationprocess(submittedorinpress),andafurther15 inpreparation; INTARESEmadecontributionstonumerousinternaltrainingcoursesinmember institutions (e.g., master's courses in the University of Utrecht and Imperial College London) and to external courses, including (i) a summer school in geographical information systems (GIS) and social and environmental epidemiology, Australian University of Technology, Canberra (April 2008); (ii) theMasterofPublicHealth,EcoledesHautesEtudesenSantéPubliqueinParis (January 2009); (iii) a summer school on spatial analysis in epidemiology and health risk assessment, London (June/July 2009); (iv) several courses on risk assessment and open assessment at the Finnish National Institute for Health andWelfareinKuopioandHelsinki(20072010); Theprojecthasformedamajorelementof11PhDtheses. 169 Coordinator: x ImperialCollegeofScience,TechnologyandMedicine,London,UK(Prof.David Briggs) Otherbeneficiaries: Organisation Country LondonSchoolofHygieneandTropicalMedicine UK NationalInstituteforPublicHealthandtheEnvironment(RIVM), NL Bilthoven UtrechtUniversity NL FrenchAgencyforEnvironmentalandOccupationalHealth FR Safety(AFSSET),MaisonsAlfort NationalInstituteforHealthandWelfare(THL),Kuopio FI NorwegianInstituteforAirResearch(NILU),Kjeller NO IT RomeEnvironmentalHealthAuthority NationalandKapodistrianUniversityofAthens EL HelmholtzResearchCentreforEnvironmentalHealth,Munich DE InstituteofAppliedScientificResearch(TNO),Delft NL KarolinskaInstitute,Stockholm SE EarthSciencesInstitute'JaumeAlmera',Barcelona ES WorldHealthOrganisation,Rome IT CatholicUniversityofLouvain,Brussels BE ES MunicipalInstituteofMedicalResearch(IMIM),Barcelona MaastrichtUniversity NL HealthProtectionAgency,London UK InstituteofExperimentalMedicine,Prague CZ FlemishInstituteforTechnologicalResearch(VITO),Mol BE NationalInstituteofPublicHealth,Prague CZ VincaInstituteofNuclearSciences,Belgrade RS SlovakMedicalUniversity,Bratislava SK DE UniversityofStuttgart NationalInstituteforHealthSurveillance(INVS),StMaurice FR NationalInstituteforIndustrialEnvironmentandRisks(INERIS), FR VerneuilenHalatte NationalCentreforPreventionofHeatHealthEffects,Rome IT ChemicalProcessEngineeringResearchInstitute, EL ThermiThessaloniki EuropeanChemicalIndustryCouncil(CEFIC),Brussels BE FR FrenchBuildingResearchandTechnologyInstitute(CSTB), ChampssurMarne BarcelonaSciencePark ES ICConsultantsLtd,London UK NetherlandsEnvironmentalAssessmentAgency,Bilthoven NL 170 CONTRACTNUMBER:505368 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST: €1895802 ECCONTRIBUTION:€1200000 STARTINGDATE:January1,2004 ENDDATE:January31,2007 DURATION:37months METHODEX METHODSANDDATAONENVIRONMENTAL ANDHEALTHEXTERNALITIES:HARMONISING ANDSHARINGOFOPERATIONALESTIMATES Summary: Major advances have been made in recent years in the analysis of externalities, particularly through the EXTERNE project. Following on from this, the key objectives of the METHODEX project were to: (i) expandtheEXTERNEmethodologyconsistentlyintoothersectorsbeyondenergyand transport,focusingonwaste,industryandagriculture;(ii)demonstratetheapproach with case studies and identify remaining research gaps; (iii) explore and produce guidance on benefit transfer, particularly for transferring values or study results betweentheEU15andNewMemberStates;(iv)engagepolicymakersanddevelop toolsforconsistentandharmonisedexternalityassessment.TheMETHODEXproject madeamajorcontributiontothedevelopmentofexternalitiesinthewaste,industry, and agricultural sectors. This recognises that externalities in these sectors are potentially important, but have received limited attention to date. To extend the current EXTERNE ‘best practice’ approach into these areas, the study undertook a detailedliteraturereviewoftherelevantstudiesinthesenewsectors,andsurveyed the methodologies used. Based on the review, the project identified the ‘priority burdens’ for each of the three new sectors, i.e., the key impacts. The study also developed harmonised approaches for quantification of the external costs of air pollutants for the three new sectors. Finally, the project investigated innovative approaches for assessing greenhouse gas externalities and communicating the uncertaintyaroundtheseestimates.Theprojectalsoinvestigatedtheextensionand transferabilityofexternalityvaluesormethods(benefittransfer)totheenlargedEU. Finally, to improve the consistency and harmonisation of future externality applications,theprojecthasdevelopedapolicytool. Potentialcontributiontothefollowingpolicies: x Thematicstrategyonairpollution[COM(2005)446] x Directive 2001/81/EC on national emission ceilings for certain atmospheric pollutants x EUwastepolicies EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 171 Mainresults: x MethodEx policy study database: The METHODEX RED policy study database was intended as a documental and bibliographic database that includes previousstudiesorpapersdealingwiththeexternalitiesresearch.Thedatabase wasprovidedasasourceofinformationforotherstouse,providingdetailsof the studies, their abstracts, and allows searches by sector, author, or title, to enabletheinformationtobeaccessedbyotherresearchersorpolicymakers; x Benefittransferguidance:Thebenefittransferguidancewasintendedtohelp improve the reliability and consistency associated with valuation benefit transfer.Theguidanceisprovidedasasourceofinformation; x Policy toolbox: The METHODEX policy toolbox was intended as a simple harmonised tool for improving the consistency of externality assessment. The toolboxwasprovidedasasourceofinformationforotherstouse,providinga range of applications to allow quantification of externalities and socio economic analysis studies. It includes an update of the air quality externality damagecostvalues(updatedBeTa)tool,aswellasarangeofotherusefultools andlinks. Coordinator: x AEATechnologyPlc,Didcot,UK(Mr.DanielForster) Otherbeneficiaries: Organisation Country PaulWatkissAssociatesLtd,Oxford UK TheCleanAirActionGroup,Budapest HU UniversityofHamburg DE InstituteofOccupationalMedicine,Edinburgh UK UniversityofStuttgart DE EMRC,Reading UK SwecoGrønerAs,Oslo NO CharlesUniversity,Prague CZ InstituteofStudiesfortheIntegrationofSystems,Rome IT Armines,Paris FR PL UniversityofWarsaw UniversityofBath UK 172 CONTRACTNUMBER:3956 PROJECTTYPE:Integratedproject TOTALPROJECTCOST: €14413490 ECCONTRIBUTION:€10000000 STARTINGDATE:November1, 2004 ENDDATE:October31,2009 DURATION:60months NOMIRACLE NOVELMETHODSFORINTEGRATEDRISK ASSESSMENTOFCUMULATIVESTRESSORSIN EUROPE Summary: The NOMIRACLE project developed new methodsforassessingtheinteractionsofpollutantsandotherstressorswhichmay affect human health as well as the environment. The projectusedtheterm‘cumulativeriskassessment’,which can be defined as an analysis, characterisation, and possiblequantificationofthecombinedriskstohealthor the environment from multiple agents or stressors. The NOMIRACLEprojectaddressedthefollowingseriesofmajorshortcomingsthatexist within the current assessment approaches: (i) they bear on direct effects of single compounds or products; (ii) they deal with uncertainty by applying default assumptions(‘safetyfactors’),whicharenotstrictlybasedonscientificprinciples;(iii) they do not account for multiple stressors and indirect effects in a dynamic and heterogeneous environment; (iv) they typically do not account for cumulative (integratedovertime,space,substances)effects;and(v)theydonotallowforsite specific and other spatially detailed evaluations. Although it is generally acknowledgedthatcombinedchemical,biologicalandphysicalstressorscancausea variety of human health or ecological health effects, assessing the risks associated with them will require considerably more complex methodological and computationaltoolsthanthoseappliedincurrentriskassessmentpractices.Thekey task of NOMIRACLE has been to meet and overcome such shortcomings, by developing novel methods and an overall conceptual framework for such complex riskassessments.NOMIRACLEresultsarethusofessentialvaluetogovernmentaland industrialregulatorsandtothescientificcommunity.Theworkhasresultedinnew tools and methods, scientific findings and draft guidance documents. The new 8 methodsarepubliclyavailableintheNOMIRACLEtoolboxonthewebsite . Potentialcontributiontothefollowingpolicies: x x x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) Regulation (EC)1272/2008 on classification, labelling and packaging of substancesandmixtures EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 8 http://nomiracle.jrc.ec.europa.eu 173 Mainresults: x New tools that improve current risk assessment procedures have been developed; x Improvedmechanisticunderstandingofmixtureeffectsandnewtoolshasbeen gainedtodescribeandpredicteffectofchemicalmixtures; x Improved understanding of the interactions between substances and natural stressors(e.g.,temperature)hasbeenachieved; x Newtoolsthatfocusonthereceptor(individualorecosystem)astheintegrator ofmultiplestressorsinspaceandtime(e.g.,vulnerabilityconceptandspatially explicit exposure models) have been developed. The tools integrate human healthandecologicalriskassessment.Theexperimentalworkhasbeenbased on analyses including a series of animal phyla, mammalian models (rodents) andhumancelllines.Theseindicatorswillgenerallybeapplicableasproxiesfor the assessment of cumulative stressors, thereby contributing to the epidemiologicalassessmentofhumanpopulationhealth; x TheapplicationoftheNOMIRACLEframeworkforcomplexriskassessmentswill greatlyimproveunderstandingoftheeffectsofcumulativeexposuresoccurring under the variety of field conditions within Europe and will thus provide a better scientific basis for forecasting risks and associated uncertainties. The understanding of the complexity of cumulative risks is a prerequisite for the development of more efficient guidelines on producing data for future regulationofchemicals; x ThenewmethodsarepubliclyavailableintheNOMIRACLEtoolboxavailableat http://nomiracle.jrc.ec.europa.eu; x The work has resulted in new tools and methods, scientific findings and draft guidancedocuments; x Theworkhasbeendocumentedinabout200reports,by28PhDprojects,and about 200 scientific peerreviewed papers. Some further 100 peerreviewed paperswillbeproducedaftertheendoftheproject; x A series of review papers on the results obtained in the key areas of NOMIRACLE have been published as a special issue on risk assessment of the peerreviewed journal Science of the Total Environment (vol. 408, pp. 3719– 3724,2010); x Duringtheprojectperiod6openinternationalworkshopsorconferenceshave been organised, and a specialised workshop resulted in a book on mixture toxicity. 174 Coordinator: x AarhusUniversity,Aarhus,DK(Prof.HansLøkke) Otherbeneficiaries: Organisation NaturalEnvironmentResearchCouncil,Wallingford HelmholtzCentreforEnvironmentalResearch,Leipzig RadboudUniversity,Nijmegen UniversityofPiemonteOrientale"AmedeoAvogadro",Vercelli VUUniversity,Amsterdam NationalInstituteofPublicHealth,Prague King'sCollegeLondon UniversityofCambridge JagiellonianUniversityMedicalCollege,Cracow UniversityofTübingen EberhardKarlsUniversity,Tübingen WageningenUniversity AveiroUniversity UniversityofAntwerp WRcLtd,Swindon LEMNATECGMBH,Würselen UniversityofSalzburg EuropeanCommission,JointResearchCentre(JRC),Ispra FinnishEnvironmentInstitute,Helsinki KaunasUniversityofTechnology AlterraBv,Wageningen SwissFederalInstituteofTechnology,Zürich NationalInstituteforPublicHealthandtheEnvironment(RIVM), Bilthoven LimCoInternational,Ibbenbüren RWTHAachenUniversity ECTOekotoxikologieGmbH,FlörsheimamMain UniversityofMilan,Bicocca EnvironmentParkSPA,Turin LausanneInstituteofTechnology(EcolePolytechniqueFédérale deLausanne) LancasterUniversity StockholmUniversity DialogikGmBH,Stuttgart Rovira&VirgiliUniversity,Reus LHASALTD,Leeds Bourgas'ProfessorAssenZlatarov'University,Bourgas SpanishNationalResearchCouncil(CSIC),Barcelona UniversityofSouthampton SymlogdeFranceInstitute,Cachan 175 Country UK DE NL IT NL CZ UK UK PL DE DE NL PT BE UK DE AT IT FI LT NL CH NL DE DE DE IT IT CH UK SE DE ES UK BG ES UK FR 176 CONTRACTNUMBER:22957 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€2998354 ECCONTRIBUTION:€1865000 STARTINGDATE:April1,2006 ENDDATE:December31,2009 DURATION:45months QALIBRA QUALITYOFLIFEINTEGRATEDBENEFIT ANDRISKANALYSISWEBBASEDTOOLFOR ASSESSINGFOODSAFETYANDHEALTH BENEFITS Summary: 9 The strategic goal of QALIBRA was to developasuiteofquantitativemethodsfor assessingandintegratingbeneficialandadverseeffectsoffoodsandapplythemto selected food groups. The project developed a generalised modular approach to benefitrisk analysis using menus of dose response and valuation functions. These covered different types of positive and negative health effects that are commonly encountered in food safety assessment. The valuation functions integrated positive and negativehealtheffectsusingcommonmeasuresofnethealthimpact(e.g.,Disability AdjustedLifeYears(DALYs).ThebenefitriskanalysismethodsdevelopedinQALIBRA wereimplementedinwebenabledsoftwareavailableforusebyallstakeholdersvia anintegratedwebsite,withdifferentcomponentsadaptedtodifferentusergroups. The methods and software developed by QALIBRA were used to carry out detailed case studies on the benefits and risks of oily fish and functional foods. The project establishedinformationsharingandjointactivitieswithBENERIS,anotherEUfunded presentedelsewhereinthispublication. Potentialcontributiontothefollowingpolicies: x EuropeanEnvironmentandHealthStrategy[COM(2003)338] x CommunityStrategyforEndocrineDisruptersCOM(1999)706final x Council Regulation (EEC)315/93 laying down Community procedures for contaminantsinfood;CommissionRegulation(EC)1881/2006settingmaximum levelsforcertaincontaminantsinfoodstuffs EUfunding: x 'Foodqualityandsafety'thematicpriority 9 www.qalibra.eu 177 Mainresults: x The consortium developed further an overall framework for benefitrisk analysis, using common currencies such as DisabilityAdjusted Life Years (DALYs)toquantifythebalanceofriskandbenefit,andprovidingtheoptionto quantifyuncertaintyineveryelementofthecalculation.Theprincipaloutputs of QALIBRA include comprehensive documentation and guidance on the framework and a userfriendly, webbased software that implements the QALIBRA framework and methods and makes them available for use by stakeholders; x The QALIBRA consortium decided that, as other software packages (e.g., Proast) already provide menus of doseresponse models, it would be more efficienttoequiptheQALIBRAwebtoolwithaflexibleinterfacetoacceptinput from any form of doseresponse model, rather than duplicate the existing functions.Thisflexibleapproachisanovelwaythatallowstheendusertobein charge of the final datasets that are going to be used for the calculations withoutanycompromisinginusageofstandardisedfunctions; x Work on the overall framework has included evaluation of doseresponse models and functions for integrating and valuing health impacts, selecting thosemostrelevanttofoodsafetyquestionsandrefiningforuseinthegeneral framework. After discussing the options and the data demands within the consortium, disabilityadjusted life years (DALYs) were regarded as the most suitablemethodtointegratethepositiveandnegativeeffectsof certainfood intakes.However,theQALIBRAframeworkandsoftwarealsoprovideforuseof themainalternative,qualityadjustedlifeyears(QALYs); x Theconsortiumidentifiedsuitablemethodsforcharacterisingthemaintypesof uncertainty affecting food benefitrisk assessments, and incorporated them in theframework; x QALIBRA investigated the benefitrisk information needs and reactions of technical users and developed solutions for effective benefitrisk communicationstrategies.Considerabletheoreticaladvanceshavebeenmade in the understanding of consumer decisionmaking associated with food consumption choices, in particular under circumstances where both risks and benefitsareinvolvedormayaccruetohumanhealth; x The QALIBRA methods and approaches were implemented as webbased software for assessing and communicating net health impacts, and detailed testingconductedwithendusers.Thesoftwarewasrefinedinresponsetoend userteststomakeitasuserfriendlyaspossible; x The QALIBRA webbased software for benefit and risk assessment of food is availableatwww.qalibra.eu. 178 Coordinator: x Matísltd,Reykjavik,IS(Dr.HelgaGunnlaugsdottir) Otherbeneficiaries: Organisation FoodandEnvironmentResearchAgency,York NationalInstituteforPublicHealthandtheEnvironment (RIVM),Bilthoven WageningenUniversity UniversityofPatras,PlataniPatras AltagraBusinessServicesandTravelAgencyLtd.,Gödöllo NationalResearchInstituteonAgricultureandFisheries (IPIMAR),Olhão 179 Country UK NL NL EL HU PT 180 CONTRACTNUMBER:506446 PROJECTTYPE: Integratedproject TOTALPROJECTCOST: €14628101 ECCONTRIBUTION: €11576001 STARTINGDATE:April1,2004 ENDDATE:June31,2008 SAFEFOODS PROMOTINGFOODSAFETYTHROUGHANEW INTEGRATEDRISKANALYSISAPPROACHFOR FOODS Summary: 10 SAFE FOODS focused on the improvement of riskassessmentmethodsandriskanalysispracticesforfoodsproducedbydifferent production practices and with different breeding technologies. The main objectives of the project were to: (i) design a European working procedure for early identification of emerging chemical or microbial risks in food production chains; (ii) develop comparativesafetyassessmentmethodsforfoodsproducedby differentbreedingapproachesandproductionpractices,using modern profiling techniques and new qualitative and quantitative riskbenefit assessment models; (iii) investigate consumers confidence/preferences in risk analysis practices for foods, including labelling and nutrition issues; (iv) understand differences in food risk perceptions of consumers, experts, and decisionmakers, and to design informative risk communication strategies; (v) investigate the role of institutions across Europe involved in risk assessment and management; (vi) design a new risk analysis approach for foods, integrating scientific principles, societal aspects and effective public participation; (vii) apply, where necessary and appropriately, the different research activities completed.Themajoroutcomeoftheprojectwasanewriskanalysisapproachfor foods that integrates assessment of human health aspects, consumer preferences and values, as well as impact analysis of socioeconomical aspects. The strength of the model is the transparent and novel way of risk identification and assessment using newly developed methods, and the inclusive way of risk management with active involvement of all stakeholders, taking a broad range of ethical, social and economicalfactorsintoaccount. Potentialcontributiontothefollowingpolicies: x EuropeanEnvironmentandHealthStrategy[COM(2003)338] x Globalfoodsafetylegislation EUfunding: x 'Foodqualityandsafety'thematicpriority 10 www.safefoods.wur.nl 181 Mainresults: x First comparative, interoperable, and userfriendly databases for profiling of foodsproducedbydifferentbreedingapproachesandproductionsystemswere designed; x Auserfriendly,transparent,andeasytouseworkingprocedurewasdeveloped for the identification of new emerging chemical and microbial risks in food productionchains; x New approaches for risk modelling of food contaminants and natural toxins, and the development of criteria for comparative risk analysis, including the validationofthestatistics,wereattempted; x Analysis of food safety risk perceptions of experts, regulators, consumers and otherstakeholdersregardingnovelandconventionalfoods,includinglabelling andnutritionalaspectsandvalidationofthestatistics,wascarriedout; x Analysisofuncertaintiesinriskassessmentandidentificationofbestpracticein communicating risk uncertainty with the public was undertaken, by linking it alsotolabellingandnutritionalissues/policies; x Consumer preference for risk analysis strategies for foods across Europe, includinglabellingandnutritionalinfluenceswereidentified; x Userfriendly guidance for evaluation and governance of systemic food risks, showinghowlabellingandnutritionalaspectsareincluded,hasbeenprovided; x Realistic, practical, and costeffective recommendations for improvement in risk management procedures and institutional structure, including their influences/linkstolabellingandnutrition,havebeenproduced; x New risk analysis approach for food safety management that integrates risk assessment of human health, consumer preferences and values, impact analysis of socioeconomical aspects andnutrition as well as labelling issues, basedonqualitativeandquantitativemethodologies,hasbeenproposed; x Fourelearningmodulesareavailableandcanbefreelyaccessedattheproject website. 182 Coordinator: x DutchInstituteofFoodSafety(RIKILT),Wageningen(Dr.HarryKuiper) Otherbeneficiaries: Organisation ScottishCropResearchInstitute,Dundee TechnicalUniversityMunich UniversityofKuopio PlantBreedingandAcclimatisationInstitute,Blonie ItalianNationalHealthInstitute(ISS),Rome CouncilforScientificandIndustrialResearch,Pretoria BiomathematicsandStatisticsScotland,Edinburgh ChineseAcademyofAgriculturalSciences,InstituteofCrop GermplasmResources,Beijing AshtownFoodResearchCentre CatholicUniversityofPiacenza PVDFoodandVeterinaryService,Riga CentralFoodResearchInstitute,Budapest NationalInstituteforPublicHealthandtheEnvironment(RIVM), Bilthoven GermanFederalInstituteforRiskAssessment(BFR),Berlin SwissFederalOfficeofPublicHealth,Bern SwedishNationalFoodAdministration,Uppsala ChineseNationalInstituteofNutritionandFoodSafety,Beijing RoyalVeterinaryandAgriculturalUniversity(KVL),Frederiksberg NationalInstituteofPublicHealth,Prague WageningenUniversity InstituteofFoodResearch,Norwich TechnicalUniversityofDenmark,KongensLyngby DialogikGmBH,Stuttgart AgriculturalUniversityofAthens UniversityofSussex,Brighton MaastrichtUniversity UniversityofGothenburg King'sCollegeLondon HungarianAcademyOfSciences,InstituteforSociology,Budapest UniversityofRome"TorVergata" EuropeanFoodInformationCouncil,Brussels UtrechtUniversity FrenchNationalInstituteforAgriculturalResearch(INRA), AgroParisTech,Paris NorwegianFoodResearchInstituteMatforsk,Ås SPIPortugal,Porto A.N.BakhInstituteofBiochemistryoftheRussianAcademyof Science,Moscow 183 Country UK DE FI PL IT ZA UK CN IE IT LV HU NL DE CH SE CN DK CZ NL UK DK DE EL UK NL SE UK HU IT BE NL FR NO PT RU 184 CONTRACTNUMBER:6529 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€998854 ECCONTRIBUTION:€998854 STARTINGDATE:January1,2006 ENDDATE:June30,2009 DURATION:42months c VERHICHILDREN VALUATIONOFENVIRONMENTRELATED HEALTHIMPACTSFORCHILDREN:ACCOUNTING FORDIFFERENCESACROSSAGE,LATENCYAND RISKCATEGORIESWITHAPARTICULARFOCUS ONCHILDREN Summary: Thesmallnumberofeconomicvaluationstudiesestimatingthebenefitsofpollution control policies for children‘s health provides little guidance for environmental policymaking.Indeed,existingvaluesusedformonetisationofenvironmentalhealth impactsfocusonadultpopulations,applyingscenariosthatoftendonotmatchwell with environmental settings. As such, there is a concernthatthecontinueduseofsuchestimatesmay result in misguided policymaking and prioritisation. Theobjectiveofthisprojectwasthereforetoimprove the incorporation of environmentrelated health impacts for children in environmental policymaking. In addition to methodological contributions to the valuation of environmentrelated health impacts for children, the work undertaken in the context of the VERHI project contributed to the development of regulatory standards, to policy development, and to risk assessment and communication strategy.Apublication'ValuationofEnvironmentRelatedHealthRisksforChildren', summarising the main results and policy implications of the project, is available on 11 theprojectwebsite . Potentialcontributiontothefollowingpolicies: x Economicandhealthbenefitsofenvironmentalpolicies EUfunding: x 'Scientificsupporttopolicy'programme 11 www.oecd.org/env/social/envhealth/verhi 185 Mainresults: x x x Estimation of values specific to children: It is reasonable to think that differencesbetweentheestimatedValueofaStatisticalLife(VSL)foradultand child populations are attributable in part to differences in age. However, age differences do not capture all of the potential sources for differences in VSL betweenadultandchildpopulations.Thedistinctiveroleofchildrenwithinthe household,therelativeimportanceofpaternalaltruism,andotherfactors(i.e., the degree of voluntariness of exposure or perceptions of dread) may well affect VSL for children relative to adults in a manner which is distinct from simple differences in age. Unfortunately, there is a paucity of research in this area.Thisleaveslittleguidanceforpolicymakersonhowtovaluehealthrisks to children. Due to the lack of empirical research on VSL, most economic analysesrelyonadultVSLestimatesforchildren‘shealtheffects.Theresearch hascontributedtofillingthisgapbyobtainingvaluesspecificallyforchildren; Ratioofvaluesforchildrenandadults:Whilethereislikelytobeasignificant degreeofuncertaintyassociatedwithanyspecificvaluesobtained(whetherfor adultsorchildren),theratioofvaluesobtainedfromastudy,inwhichtheVSLs estimated for both adults and children are directly comparable, can assist policymakers in their evaluation of policies which affect both populations. In principle, the marginal rate of substitution (MRS) between the estimated VSL forachildandforanadultcanbeusedtoadjustestimatedbenefitsforpolicy and programmes should the MRS not equal one. However, clearly more researchisrequired,andtheresultsofVERHIrepresentacontributiontothis literature; Contribution to methodological development: The values obtained are, of course, important outcomes from the project. However, there are important and contentious methodological issues, which need to be addressed when valuing environmental health impacts differentiated according to risk and individual characteristics. As such, through the preparation of the methodologicalreviews,theveryextensivesurveydevelopmentwork, aswell as the empirical work itself, it is anticipated that the project will also make a moregeneralcontributiontodevelopmentsinthestateoftheartinthisarea. Thus, by providing guidance on how to undertake such studies in the future, the outcomes of the project will be of broader relevance to the research and policycommunities. Coordinator: x Organisation for Economic Cooperation and Development (OECD), Paris, FR (Dr.NickJohnstone) Otherbeneficiaries: Organisation EniEnricoMatteiFoundation,Milan UniversityofEastAnglia,Norwich CharlesUniversity,Prague Country IT UK CZ 186 CHAPTERIVProjectsFocusedontheDevelopmentofinvitroToxicityTestingStrategies CHAPTERIV Projectsfocusedonthe developmentofinvitrotoxicity testingstrategies 187 188 CONTRACTNUMBER:512051 PROJECTTYPE:Integratedproject TOTALPROJECTCOST:€12112179 ECCONTRIBUTION:€7664665 STARTINGDATE:January1,2005 ENDDATE:June30,2010 DURATION:66months ACUTETOX OPTIMISATIONANDPREVALIDATIONOF ANINVITROTESTSTRATEGYFOR PREDICTINGHUMANACUTETOXICITY Summary: ThemainobjectivesofACUTETOXincluded the compilation, evaluation and generation of high quality in vitro and in vivo data on a set of reference chemicals for comparative analyses, and the identification of factors that influence the correlation between in vitro (concentration) and in vivo (dose) toxicity, particularly taking into consideration biokinetics, metabolism and organ toxicity (liver,centralnervoussystem,kidney).Moreover,innovative tools (e.g., cytomics) and new cellular systems for anticipating animal and human toxicity were explored. Ultimately,thegoalwastodesignasimple,robustandreliableinvitroteststrategy amendableforrobotictesting,associatedwiththepredictionmodelsforacuteoral toxicity.Theoutcomeofthefirstphaseoftheprojectwasalargetoolboxofinvitro methods with associated optimised protocols. A list of eight in vitro and in silico methods, which are the most promising candidates for inclusion in proposal of potentialtestingstrategies,wasgenerated.Duringthelatterpartoftheproject,five proposals for in vitro tiered testing strategies were formulated and evaluated in terms of predictivity. Some of the knowledge derived from the project has been already applied in the daily activities of companies which are ACUTETOX partners (e.g., pharmaceutical sector). More information is available on the project website andacatalogue' AlternativeTestingStrategiesProgressReport2011'. Potentialcontributiontothefollowingpolicies: x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x Directive2010/63/EUontheprotectionofanimalsusedforscientificpurposes. EUfunding: x 'LifeSciences,GenomicsandBiotechnologyforHealth'thematicpriority 189 Mainresults: x ACUTETOX undertook the challenging goal to create an integrated testing strategy to replace the animal testing used today for predicting human acute oral systemic toxicity, which is based exclusively on in vitro and in silico methods; x Theprojectrepresentsthefirstattempttoprevalidateatestingstrategybased exclusively on nonanimal methods; therefore, it provided an excellent case study for the European Centre for the Validation of Alternative Methods (ECVAM) and helped to progress the discussions on validation of testing strategies,whicharecurrentlyongoingatseverallevels.Indeed,thiscasestudy has been already presented at the European Partnership for Alternative Approaches to Animal Testing (EPAA)/ECVAM workshop on Validation of IntegratedTestingStrategiesin2009; x Inthefirstphase oftheproject,a verylargenumber ofin vitrotestmethods (approximately 75 endpoints) have been evaluated in terms of their within laboratory variability (and in some cases also the betweenlaboratory variability), preliminary predictive capacity and the potential to identify alerts fororganspecifictoxicity.Theoutcomeofthisphaseoftheprojectwasalarge toolboxofinvitromethodswithassociatedoptimisedprotocols,someofthem evaluatedtothelevelofprevalidation; x An indepth statistical analysis of the large dataset generated in this project resulted in a list of 8 in vitro and in silico methods, which are the most promisingcandidatesforinclusioninaproposalofpotentialtestingstrategies. Protocols of all these methods will be available to the public as INVITTOX protocols(Databankofinvitrotechniquesintoxicology),throughtheECVAM databaseonalternativemethods(DBALM); x The last phase of the project focused mainly on the assessment of the predictive capacity of the proposed tiered testing strategies and the identification of assay combinations that give the best prediction in terms of classifying chemicals into the official acute oral toxicity categories. Five proposalsforinvitrotieredtestingstrategieswereformulatedandevaluatedin termsofpredictivity; x The outcome of this analysis reinforced previous results obtained with the 3T3/NRU assays and supports the use of this validated cytotoxicity assay to identifyunclassifiedsubstances(LD50>2000mg/kg),asafirststepinatiered testingstrategy; 190 x x x Several in vitro assays have proved to be useful to identify alerts for tissue specific toxicities such as neurotoxicity and nephrotoxicity. However, the resultsoftheclassificationanalysisshowedthatcomplementingthe3T3/NRU assaywiththoseinvitroassaysdoesnotimprovesignificantlytheclassification of compounds in toxicity categories 14. This outcome is largely linked to the factthatthecurrentclassificationsystemsarebasedonarbitrarilyassignedcut offs for the rat LD50 values and do not include more detailed scientific (mechanistic) information on the compounds. Thus, a revision of the current classifications schemes might be advisable and should be put forward to the Europeanregulatoryagencies; Mostoftheresultsobtainedinthecourseoftheprojecthaveresultedinpeer reviewed publications, which proves the scientific quality of the data generated; Some of the knowledge derived from the project has been already applied in the daily activities of companies, which are ACUTETOX partners (e.g., pharmaceuticalsector).ThisgoesbeyondthemainobjectiveoftheACUTETOX project (prediction of acute oral toxicity) and helps to improve European competitiveness. 191 Coordinator: x OuluUniversity,FI(Dr.LeilaRisteli) Otherbeneficiaries: Organisation EnvironmentalCompetenceABExpertrådet,Sollentuna LaFeUniversityHospital,Valencia EuropeanCommission,JointResearchCentre(JRC),Ispra NosciraSA,Madrid UtrechtUniversity BiovitrumAB,Stockholm UniversityofNottingham UniversityofValencia CentreforBioActiveMoleculesScreening(CMBA),Grenoble CentreforEnergy,EnvironmentandTechnologyResearch (CIEMAT),Madrid CatholicUniversityofLouvain,LouvainlaNeuve InstituteofBiomedicalResearch,Barcelona InstituteofPublicHealth,Brussels AdvancedInVitroCellTechnologies,Barcelona StockholmUniversity BayerHealthCareAG,Wuppertal UniversityofAberdeen UniversityofLausanne FreeUniversityofBrussels GAIKER,Zamudio RoyalInstituteofTechnology,Stockholm UniversityCollegeDublin UmeåUniversity ItalianNationalHealthInstitute(ISS),Rome UniversityofZürich FraunhoferInstitute,Hannover PalackýUniversity,Olomouc InVitroTestingIndustrialPlatform,Rotterdam UniversityofKonstanz UppsalaUniversity ArtoisUniversity,Lens SwedishFundforResearchwithoutAnimalExperiments,Älvsjö UniversityofBarcelona 192 Country SE ES IT SE NL SE UK ES FR ES BE ES BE ES SE DE UK CH BE ES SE IE SE IT CH DE CZ NL DE SE FR SE ES CONTRACTNUMBER:22674 PROJECTTYPE:Specifictargeted researchproject TOTALPROJECTCOST: €2424954 ECCONTRIBUTION:€1464692 STARTINGDATE:April1,2006 ENDDATE:March31,2009 DURATION:36months CAESAR COMPUTERASSISTEDEVALUATIONOF INDUSTRIALCHEMICALSUBSTANCES ACCORDINGTOREGULATIONS Summary: 1 One of the principal aims of the CAESAR project was to build models to predict toxicity of chemical substances for the REACH regulation. A secondary goal was to reduce animal testing and, in consequence, the cost of these tests. The third objective was to gain wide applicability and acceptability of these models by stakeholders for decision support. CAESAR developed new quantitative structureactivity relationship (QSAR) models specific for REACH for five endpoints: bioconcentration in fish; skin sensitisation, mutagenicity, carcinogenicity; and developmental toxicity. These models have been plannedtoallowaneasyaccessanduse:industryandregulatorscanfreelyusethe models through the internet. Three simple steps allow the user to introduce the chemical(s),gettheprediction,andsaveorprinttheresult.TheCAESARmodelsare soundandscientificallybased:Globally,dataonabout7000compoundswereused to build up the models. The chemical structures have been individually double checked.Outofanumberofmodelsdeveloped,thebestwerechosenandvalidated. The models provide guidance on how they can be applied. The models can run hundredsofcompoundsinabatchwithinafewseconds,startingfromverysimple andeasilyavailablechemicalformatssuchasSMILEsandsdf. Potentialcontributiontothefollowingpolicies: x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x Directive2010/63/EUontheprotectionofanimalsusedforscientificpurposes EUfunding: x 'Scientificsupporttopolicy'programme 1 www.caesarproject.eu 193 Mainresults: x CAESAR developed and made freely available quantitative structureactivity relationship(QSAR)modelsforfiveendpoints,specificallydesignedforREACH. The endpoints are: bioconcentration factor, skin sensitisation, mutagenicity, carcinogenicityanddevelopmentaltoxicity(teratogenicity); x The results of predictions were superior or equivalent to those obtained with other commercial or public models. Thus, new independent models are now availablefortoxicityandpropertypredictionsofindustrialchemicals; x The models are based on experimental data. Highquality data was used, verifying individually all structures, in order to have a robust basis for the models.Themodelshavebeenvalidatedwithexternaltestsetsandaseriesof statisticalmethods; x The models predict a continuous value or a category (such as toxic or not), dependingontheendpointandREACHrequirements.Themodelsarebasedon aseriesoffragmentsormoleculardescriptors,anduseseveralalgorithms; x The models have been optimised to be reproducible, transparent, freely available,validated,andtailoredforREACH(inputdataofhighquality,output datasuitableforclassificationandlabelling,prioritisationandriskassessment); x Aseriesofcollaborationswereinitiatedwithregulators,industryandscientists. TheseincludetheUSEnvironmentalProtectionAgency,theItalianFederation of Chemical Industry Federchimica and the EUfunded projects OSIRIS (describedelsewhereinthiscatalogue),CHEMPREDICT(DevelopmentofFreely Available Predictive Models Based on Simple Chemical Descriptors), CHEMOMENTUM (Grid services based environment to enable innovative research)andCASCADE(describedelsewhereinthiscatalogue). Coordinator: x Institute of Pharmacological Research Mario Negri, Milan, IT (Prof. Emilio Benfenati) Otherbeneficiaries: Organisation Country CentralScienceLaboratory,York UK BiochemicsConsultingSAS,Olivet FR MilanPolytechnicInstitute IT KnowledgeMinerSoftware,Panketal DE LiverpoolJohnMooresUniversity UK HelmholtzCentreforEnvironmentalResearch,Leipzig DE NationalInstituteofChemistry,Ljubljana SI InstituteofAppliedScientificResearch(TNO),Delft NL 194 CONTRACTNUMBER:37712 PROJECTTYPE: Integratedproject TOTALPROJECTCOST:€11986502 ECCONTRIBUTION:€10440000 STARTINGDATE:November1,2006 ENDDATE:April30,2012 DURATION:66months CARCINOGENOMICS DEVELOPMENTOFAHIGHTHROUGHPUT GENOMICSBASEDTESTFORASSESSING GENOTOXICANDCARCINOGENIC PROPERTIESOFCHEMICALCOMPOUNDSIN VITRO Summary: 2 The CARCINOGENOMICS project aimed to develop in vitro methods to test the carcinogenic properties of compounds as an alternative to the chronic rodent bioassaysthatassesschemicalgenotoxicityandcarcinogenicity.Themajorgoalwas to develop a series of mechanismbased in vitro tests that are representative of various modes of carcinogenic actionforanumberofmajortarget organsforcarcinogenicaction,e.g., liver,lungs,andkidneys.Ithasalso the objective of building an iterativeinsilicomodelofchemical carcinogenesis. This will enable the efficient assessment of high numbers of compounds for genotoxicity and carcinogenicity as required under the REACH initiative,whilereducinginvivotesting.Attheendoftheproject,akidneyRPTECT model(normalrenalproximaltubuli)wassuccessfullyfinalised.Theliverembryonic stemcellmodeldevelopedisverypromising.However,thetestingofmorechemicals is necessary as is the lung primary bronchoalveolar cell model. The project gained information on interlaboratory reproducibility of toxicogenomics assays. More informationisavailableontheprojectwebsiteandacatalogue' AlternativeTesting StrategiesProgressReport2011'. Potentialcontributiontothefollowingpolicies: x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x Directive2010/63/EUontheprotectionofanimalsusedforscientificpurposes EUfunding: x 'LifeSciences,GenomicsandBiotechnologyforHealth'thematicpriority 2 www.carcinogenomics.eu 195 Mainresults: x KidneyRPTECTmodel(normalrenalproximaltubuli)wassuccessfullyfinalised. Aclearsegregationbetweengenotoxiccarcinogensvsnongenotoxic carcinogensvsnoncarcinogenswasobserved.Anassayisreadyfor submissiontoECVAM(theEuropeanCentrefortheValidationofAlternative Methods): x Theliverembryonicstemcellmodelisverypromising.However,thetestingof morechemicalsisnecessary. x AsregardstheliverHepaRGmodel,furtherquestionswereraised.Therewasa clearsegregationbetweengenotoxiccarcinogensvsnongenotoxiccarcinogens and noncarcinogens; however, there was no clear distinction between nongenotoxiccarcinogensandnoncarcinogens; x The physiological relevance of the HepaRG system could possibly be too limited; x Noncarcinogens included some liver toxicants: there is a possible overlap in theresponsemechanismsfornongenotoxiccarcinogensandtoxicantsinthe liver; x Thelungprimarybronchoalveolarcellmodelisverypromising.Nevertheless, testingofmorechemicals,includinggases,isnecessary; x Elaborate experience was successfully gained on gathering information on interlaboratory reproducibility of toxicogenomics assays (under the supervisionbyECVAM); x Aprotocolforharmonisedbioinformaticsapproacheswasgenerated. Coordinator: x MaastrichtUniversity,NL(Prof.JosKleinjans) Otherbeneficiaries: Organisation Country LaFeUniversityHospital,Valencia ES FreeUniversityofBrussels BE Cellartis,Gothenburg SE LeidenUniversityMedicalCentre NL UniversityCollegeDublin IE Novozymes,Bagsvaerd DK ImperialCollegeofScience,TechnologyAndMedicine,London UK AdvancedInVitroCellTechnologies,Barcelona ES EuropeanBioinformaticsInstitute,Hinxton UK NL InstituteofAppliedScientificResearch(TNO),Delft MaxPlanckInstituteforMolecularGenetics DE Munich EuropeanCommission,JointResearchCentre(JRC),Ispra IT BE 196 EuropeanConsensusPlatformforAlternatives(ECOPA) Brussels Unilever,London InnsbruckMedicalUniversity GenedataAG,Basel BiopredicInternational,Rennes LiverpoolJohnMooresUniversity 197 UK AT CH FR UK 198 CONTRACTNUMBER:37168 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST: €3011664 ECCONTRIBUTION:€2173492 STARTINGDATE:October1,2006 ENDDATE:March31,2010 DURATION:42months EXERA DEVELOPMENTOF3DINVITROMODELSOF ESTROGENREPORTERMOUSETISSUESFOR THEPHARMACOTOXICOLOGICALANALYSIS OFNUCLEARRECEPTORSINTERACTING COMPOUNDS(NRICS) Summary: 3 The objective of the EXERA project was to develop novel threedimensional (3D) in vitro models of mouse tissues from five major organs for the pharmacotoxicological analysis of oestrogen receptor interacting compounds: liver, skin and bone (nonreproductive systems), ovary and testis(maleandfemalereproductivesystems). The steps to reach the objectives involved several complementary techniques: cell isolation, constitutive and conditional immortalisation, cell banking, 3Dcultures, whole genome expression profiles, in vivo imaging, and application of 3Dculture devices (Rotary cell culture system [RCCS] technology). Acute and longitudinal studies identified the consistency of reporter mouse methodology, demonstrating the direct relationship between the administered dose of the compound and the intensity of photon emission measured in different body areas targeted by nuclear receptor (NR)ligands.Theresultsfurthershowedthatbothprimarycellsandfresh tissues, as well as immortalised cells derived from reporter mice, can be cultured through 3D technologies. Investigations continue beyond the timeframe of the project. Potentialcontributiontothefollowingpolicies: x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x Council Directive on the approximation of the laws of the Member States relatingtocosmeticproducts(76/768/EEC) x CommunityStrategyforEndocrineDisruptersCOM(1999)706final x Directive2010/63/EUontheprotectionofanimalsusedforscientificpurposes EUfunding: x 'LifeSciences,GenomicsandBiotechnologyforHealth'thematicpriority 3 www.altaweb.eu/exera 199 Mainresults x The improved systems generated and exploited in EXERA propose efficient tools for the characterisation of newly synthesised drugs that interact with nuclear receptors (NRs) and for the risk assessment of industrial “hormones” thatmaycontaminatethefoodandtheenvironment; x Similartoinvitrosystems,advancedanimalmodelsmayalsofulfiltwoofthe '3Rs'ofalternativetesting:refineandreduce.Theextensionoftheconceptof the3Rstoanimalmodelsresidesintherealisticconsiderationthatthecurrent rodenttestsystemsarelikelytoremaininuseforpharmacokinetic(i.e.,dosage, formulation, administration, halflife), toxicological (systemic and organ specific) and biological evaluations of candidate therapeutics and toxic xeno compounds for years to come (in the context of REACH regulation). If appropriatelyused,however,pathwayspecificinvivomodels,suchasreporter mice, zebrafish or xenopus, while providing flexible and highly standardisable parameters,maystronglydecreasetheoverallnumberofanimalsrequired; x A first example is reporter animals for hormone actions. These models have beendevelopedduringthepastfewyearsbytheinsertionintothegenomeof DNA elements, which provide the template for recognition by NRs, furnishing major insights into the NR physiology. When used for toxicological purposes, theyrepresentsuitablemodelsforstudyingxenohormones,givingacomplete viewofthebodyregions,inwhichthesecontaminantsact.Byprovidingreliable and informative data on physiological changes without animal sacrifice, they fulfil two of the 3R’s principles ('refine' and 'reduce'). Because good reproducibilityandsensitivityhavebeenachieved,thesereportersystemsmay providenewapproachesforstudyingthetoxicodynamicsandtoxicokineticsof severalwidespreadchemicals.Acuteandlongitudinalstudiescarriedoutbythe EXERA consortium established the consistency of the reporter mouse methodology,demonstratingthedirectrelationshipbetweentheadministered dose of the compound and the intensity of photon emission measured in differentbodyareastargetedbyNRsligands; x Thepossibilityofderivinginvitrosystemsforthetissuespecificevaluationof thesamemarkersexpressedinreporteranimalsmayincreasetheefficiencyof invitro/invivocorrelations,coveringthethird'R'inalternativetesting:'replace'. Itwasshownthatbothprimarycellsandfreshtissues,aswellasimmortalised cells derived from reporter mice, can be cultured through threedimensional technologies, providing tools that generate data more similar to the in vivo situation. By reproducing specific threedimensional tissuelike structures that mimic the functions and responses of real tissues in a more physiological manner, 3D cell culture bioreactors represent a potential bridge for covering thegapbetweenanimalandhumanstudies.Thecouplingbetweenengineered human cells, 3D culture methods and new luminescence/fluorescence detection devices add further possibilities for the application of these technologiestothemodernpharmacotoxicology. 200 Coordinator: x CivicHospitalofBrescia,IT(Dr.DiegoDiLorenzo) Otherbeneficiaries: Organisation UniversityofMilan UniversityofTurku AthloneInstituteofTechnology,Athlone CELLONSA,Bereldange HormosMedicalPharmacity,Turku DNAVision,Charleroi ArchportLtd,Dublin ALTAsrl,Siena 201 Country IT FI IE LU FI BE IE IT 202 CONTRACTNUMBER:37017 PROJECTTYPE:Integratedproject TOTALPROJECTCOST: €14787639 ECCONTRIBUTION:€10000000 STARTINGDATE:April1,2007 ENDDATE:September30,2011 DURATION:54months OSIRIS OPTIMIZEDSTRATEGIESFORRISK ASSESSMENTOFCHEMICALSBASEDON INTELLIGENTTESTING Summary: 4 ThegoalofOSIRIS wastodevelopintegrated testingstrategies(ITS)fitforREACHthatmake it possible to significantly increase the use of nontesting information for regulatory decision making, and to effectively reduce animaltestingtothelevelneededfromariskperspective.Theprojecthadfivemajor objectives: (i)To develop methods andguidance for transparent and scientifically sound use of chemistrydriven information in ITS; (ii) To provide efficient strategies and guidance for exploitationofalltypesofbiologicalinformation on toxic effects of chemicals in ITS, focusing on reduced animal use and informed extrapolation across human and environmental toxicology,species,endpointsandtimescales;(iii)Todevelopcriteriafor exposure informed testing as foreseen in the REACH regulation, and to refine relevant exposure assessment methods accordingly; (iv) To develop weightofevidence approaches for ITS based on a computerised decision theory framework ready for web access, optimising the use of existing data and nontest information, and minimisingtheneedfornewtestinginriskassessmentprocedures;(v)Toevaluate the feasibility and effectiveness of the new ITS methodologies and to provide guidance for their use in concrete form, covering major human and environmental endpoints.ThecentralsoftwareoutcomeofOSIRISistheOSIRISwebtool.Thistool guidesinperformingITSonskinsensitisation,repeateddosetoxicity,mutagenicity, carcinogenicity, bioconcentration factor, and aquatic toxicity. The webtool can be accessed at http://osiris.simpple.com/OSIRISITS. To use the tool, a free online registrationisrequired. Potentialcontributiontothefollowingpolicies: x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x Directive2010/63/EUontheprotectionofanimalsusedforscientificpurposes EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 4 www.osiris.ufz.de 203 Mainresults: x The central software outcome of OSIRIS is the web tool. It includes the followingfeatures:(i)Theusercanmanagesubstances,testdata,insilicodata and physicochemical properties of the substances, and can import data from IUCLID5exportfiles;(ii)Theusercancreateassessmentsandexecutethemto evaluatesubstancesusingtheimplementedITS;(iii)Thetoolallowstheuserto manage user input elements that are required by the ITS execution; (iv) The tool has a help system and user management functions; (v) The tool is connectedwiththeOSIRISChemPropdatabase;(vi)Thetoolhasaninterfaceto import model results from the ChemProp software; (vii) Software modules to deal with advanced decision methods are provided; (viii) Exposurebased waivingandphysicochemicalwaivingareprovided; x Supported endpoints are: aquatic toxicity, bioconcentration factor, mutagenicityandcarcinogenicity,repeateddosetoxicityandskinsensitisation; x Thetoolguidestheuserthroughallthestepsrequiredtoevaluate.Toevaluate asubstance,theuserisinstructedtocreatethesubstanceinthewebtool,add knownrelevantinformationandimportdatafromIUCLID5andfromChemProp software.Thentheusercancreateassessmentsforendpoints; x Thewebtoolispubliclyavailableattheaddresshttp://osiris.simpple.com,and free online registration is required to use the tool. Registration and login is requiredbecauseuserprovideddataneedstobestoredtobeusedbythetool; x The web tool also provides a single point of access to two tools developed independently: the chemical and biological space navigation tool and the OSIRISconsensustool; x TheITSforskinsensitisationaimstohelptheuserinweighingdifferentsources of information (most of the sources mentioned in the REACH technical guidance), and to specifically help answering the following question: When is thebodyof(alternative)evidencesufficienttoreplacetherequiredREACHtest result, i.e., to replace the need for performing a local lymph node assay (LLNA)?; x TheITSRepDosewasdevelopedtoevaluatetheconditionsunderwhichanon guideline study is still reliable preventing new guideline studies. The ITS RepDoseisimplementedintheOSIRISwebtool; x TheITSformutagenicityandcarcinogenicityaredescribedindetailinanumber of OSIRIS deliverables, the most important of which is deliverable D4.2.14, availableontheprojectwebsite; x Bioaccumulationwaschosenasendpoint(i)forpracticalreasons:availabilityof experimental data to make practical testing of the scheme, availability of alternativemethodstolimitthenumber ofrequestedtests;(ii)forrelevance: data for bioconcentration are required not only to satisfy the Annexes of REACH but also for Classification and Labelling, Chemical Safety Assessment and for the prioritisation through the PBT (Persistent, Bioaccumulative and Toxic)/vPvB (Very Persistent and Very Bioaccumulative) assessment, and (iii) becauseofthesubstantialnumberofanimalsrequiredforthetests(morethan 100 fish for each substance). The proposed scheme will be of help for the 204 x x registrant because it summarises the requirements and specific condition identifiedbyREACH.Moreover,itincludesalternativemethodstohelptheuser inthechoiceofthemostappropriatestrategy; Aquatic toxicity was chosen as endpoint also for similar reasons as bioaccumulation; Workshops have established and continue a dialogue between project membersandEUstakeholders. Coordinator x HelmholtzCentreforEnvironmentalResearch,DE(Prof.GerritSchüürmann) Otherbeneficiaries: Organisation Country Rovira&VirgiliUniversity,Reus ES LiverpoolJohnMooresUniversity UK UniversityofBern CH NationalInstituteforPublicHealthandtheEnvironment(RIVM), DE Bilthoven TechnicalUniversityofDenmark,KongensLyngby DK InstituteofAppliedScientificResearch(TNO),Delft NL InstituteofPharmacologicalResearchMarioNegri,Milan IT CH Procter&GambleInternationalOperationsSa,Lancy SwissFederalInstituteofTechnology,Zürich CH ItalianNationalHealthInstitute(ISS),Rome IT UniversityofAntwerp UK VUUniversity,Amsterdam NL SIMPPLES.L.,Tarragona ES KWRWaterCycleResearchInstitute,Nieuwegein NL InstituteofPublicHealthoftheRepublicofSlovenia,Ljubljana SI EE NationalInstituteofChemicalPhysicsandBiophysics,Tallinn ECTOekotoxikologieGmbH,FlörsheimamMain DE FraunhoferInstitute,München DE AarhusUniversity,Roskilde DK StockholmUniversity SE Bourgas'ProfessorAssenZlatarov'University,Bourgas BG MerckKGaA,Darmstadt DE EcoleCentraledeLyon,Lyon FR NoferInstituteofOccupationalMedicine,ód PL IT EuropeanCommission,JointResearchCentre(JRC),Ispra UniversityofExeter UK AnalytischesLaboratoriumLuhnstedt DE DialogikGmBH,Stuttgart DE CyprotexPLC,Macclesfield UK WageningenUniversity NL 205 206 CONTRACTNUMBER:504761 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€3390254 ECCONTRIBUTION:€2259754 STARTINGDATE:September1,2004 ENDDATE:December31,2007 DURATION:40months PREDICTOMICS SHORTTERMINVITROASSAYSFOR LONGTERMTOXICITY Summary: 5 PREDICTOMICS aimedatdevelopinganovelplatformforpredictingliverandkidney chronictoxicityelicitedbydrugsandxenobiotics.Bycombining'omics'technologies andadvancedcellularmodels,PREDICTOMICSaimedtoprovidevaluabletoolsfora reliable screening of new drug candidates by the pharmaceutical industry, as well potential toxins. Using cellular models representing as well as possible the human liver and kidney in vivo and appropriate assessment procedures, a platform was developed that allows to give an early warning about chronic renal and hepatic toxicants. As regards cholestasis flow cytometry, results of three independent experiments either for noncholestasic or cholestasic compounds showed that thisassaywasabletoclassifytestedcompoundsaccordingtheirimpairmentofdrug uptake.Therefore,thisstudywasfoundrobustandreproducibleasithassupported results obtained with compounds previously tested by this method in other laboratories. Concerning steatosis flow cytometry, results of three independent experimentseitherfornonsteatosicorsteatosiccompoundsshowedthatthisassay was able to classify most of compounds tested in this assay according to their steatosiceffect,althoughmoreexperimentsshouldbeperformedtoreallyshowthe robustness of this method. More details on results are available on the project websiteandacatalogue'AlternativeTestingStrategiesProgressReport2009'. Potentialcontributiontothefollowingpolicies: x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x Directive2010/63/EUontheprotectionofanimalsusedforscientificpurposes EUfunding: x 'LifeSciences,GenomicsandBiotechnologyforHealth'thematicpriority 5 www.predictomics.com/principal.htm 207 Mainresults: x x x x Amethodtoidentifycompoundsthatmightcauselivercholestasisbymeansof afluorescencebasedcytometryhasbeendesignedandexternallyprevalidated. Themethodmonitorsrealtimekineticsuptakeofbileacidderivativesinfresh suspensionsofhepatocytesandtheimpairmentcausedbydrugs; Aseconddevelopedmethodwasa cytometrybased multiparametricassayto identifydrugscausingliversteatosis.Makinguseofastablehumanhepatoma derivedcellline(HepG2)treatedwithmodelsteatotichepatotoxinsandimage analysisafterfluorimetricquantitationofthelipidcontentofcells,aswellother cellular endpoint parameters, is was possible to distinguish among weak, moderateandstrongsteatosiccompounds; Athirddevelopedmethodmadeuseofagenomewidescaletoidentifygene products whose expression levels or posttranslational features changed as a consequence of exposure to steatosic drugs. On the basis of the results obtained,a‘steatosisfingerprint’hasbeendefinedandwillbeexploitedinthe formofaDNAmicroarray; Concerningrenaltoxicity,ahumanproximaltubulemodelhasbeenestablished for the purposes of conducting gene expression microarrays with the AffymetrixHGU133plustwoplatforms.Aninterlaboratorycomparisonacross four laboratories confirmed that the model is standardised, robust, reproducible and transferable. The predictive ability of the model with an additional 11 nephrotoxic compounds was investigated and a preliminary predictionmodeldeveloped.Anumberoflimitationsofthemodelhavebeen identified.Anumberofmarkergeneshavebeenidentifiedwhicharepotential markersofearlyresponsetotoxicity. Coordinator: x LaFeUniversityHospital,Valencia,ES(Prof.JoséV.Castell) Otherbeneficiaries: Organisation InnsbruckMedicalUniversity FreeUniversityofBrussels FrenchNationalInstituteofHealthandMedicalResearch(INSERM), Montpellier LeidenUniversityMedicalCentre UniversityCollegeDublin BayerHealthCareAG,Wuppertal ProgenikaBiopharma,S.A.,Derio PHARMAMAR,S.A.,ColmenarViejo Johnson&JohnsonPharmaceuticalResearch&Development,Beerse EuropeanConsensusPlatformon3RAlternativestoAnimal Experimentation(ECOPA),Brussels EuropeanCommission,JointResearchCentre(JRC),Ispra 208 Country AT BE FR NL IE DE ES ES BE BE IT CONTRACTNUMBER:503257 PROJECTTYPE: Integratedproject TOTALPROJECTCOST: €13334891 ECCONTRIBUTION:€9100000 STARTINGDATE:July1,2004 ENDDATE:December31,2009 DURATION:66months REPROTECT DEVELOPMENTOFANOVELAPPROACHINHAZARD ANDRISKASSESSMENTORREPRODUCTIVE TOXICITYBYACOMBINATIONANDAPPLICATION OFINVITRO,TISSUEANDSENSORTECHNOLOGIES Summary: Due to the complexity of the reproductive cycle and for the lack of validated alternative tests for most of the steps included in the cycle,testinginlivinganimalsispresentlythe only tool available for hazard assessment ofreproductive toxicants. The aim of the 6 33partner REPROTECT was to identify a novel approach to reproductive toxicity hazard assessment. The project was set up in order to develop/optimise in vitro models that are able to detect adverse effects and mechanisms associated with reproductive toxicity. The REACH regulation and the 7th amendment to the CosmeticsDirectivewillmostlikelyleadtoadramaticincreaseinanimaluseusedfor toxicitysafetytesting.Ithasbeenestimatedthatreproductivetoxicitytestingwillbe themostanimalconsumingareainthecontextofREACH.Intheperspectiveofthe large amount of testing required by the legislation, the combination of alternative testsinanintegratedtestingstrategyforreproductivetoxicityisstronglyencouraged. Within its life time, REPROTECT explored the predictive power of a range of pioneering in vitro tests. About 150 peerreviewed reproductive toxicants with differenttoxicologicalmechanismswereselectedandtestedinordertosupportthe optimisationprocessoftestprotocolsdeveloped.Moreover,inordertospeedupthe process of validation of in vitro tests and to safeguard the consistency with internationally agreed validation criteria, the test development/optimisation followed the requirements laid down in the modular approach of the European CentrefortheValidationofAlternativeMethods(ECVAM)principlesontestvalidity. More information is available on the project website and a catalogue 'Alternative Testing Strategies Progress Report 2009' and a special issue of Reproductive Toxicology(August2010). Potentialcontributiontothefollowingpolicies: x x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) Council Directive on the approximation of the laws of the Member States relatingtocosmeticproducts(76/768/EEC) Directive2010/63/EUontheprotectionofanimalsusedforscientificpurposes x EUfunding: x 'LifeSciences,GenomicsandBiotechnologyforHealth'thematicpriority 6 www.reprotect.eu 209 Mainresults: x Adverse effects on mammalian female and male fertility were predicted by more than 20 different tests reflecting various toxicological endpoints of the reproductivecycle; x EffectsonLeydigandSertolicells,folliculogenesis,germcellmaturation,sperm cells, steroidogenesis, the endocrine system, fertilisation and on the pre implantationembryowereassayedbythevarioustestsystems; x The development/optimisation of each test has been performed according to the ECVAM modular approach; INVITTOX protocols of most of the assays are availableattheendoftheproject; x An independent statistical evaluation on the raw data generated has been performedforthemajorityofthetestsinordertodefinetheirreproducibility; x The definition of teratogenicity assays using embryonic stem (ES) cells from mouse and human origin has been finalised. Proteome analyses have been performed on mouse and human ES cells treated with selected chemicals duringneuronalandcardiacdifferentiation.Thepromisingresultsobtainedwill bepublishedsoonandthepatentingofthemethodologyisplanned; x Anintegrationofametabolicsystemintotheembryonicstemcelltest(EST)has beeninvestigated.TheoutcomeofaworkshopontheESThasbeenpublished. In addition, a new reporter assay using genetically engineered mouse ES cells hasbeendeveloped; x Theprojectwasextendedfor6monthstoallowtheconductionofafeasibility study,inwhich10blindedchemicals,selectedbyanindependentexpertgroup, wereanalysedinatestbatteryapproach.Theoutcomeofthestudyindicated thattheknowninvivo(intheanimal)effectsofthe10testchemicalscouldbe mostlyeventhoughnotinallcasescorrectlypredicted; x TheresultsofthefeasibilitystudywaspublishedinAugustof2010inaspecial issueof'ReproductiveToxicology'alongwith19otherarticlesfromREPROTECT partners,whodescribeindetailtheoutcomeofsomeoftheirresultsobtained intheproject. 210 Coordinator: x UniversityofTübingen,InstituteofPharmacologyundToxicology(Prof.Michael Schwarz) Otherbeneficiaries: Organisation Country ErasmusUniversityMedicalCentre,Rotterdam NL BioDetectionSystemsBV,Amsterdam NL NationalInstituteforPublicHealthandtheEnvironment(RIVM), NL Bilthoven FreeUniversityofBrussels BE Johnson&JohnsonPharmaceuticalResearch&Development, BE Beerse SpallanzaniInstitute,Cremona IT NationalHealthInstitute(ISS),Rome IT UK ImperialCollegeofScience,TechnologyAndMedicine,London PfizerGlobalResearch,Amboise FR FederalInstituteforRiskAssessment(BFR),Berlin DE BayerHealthCareAG,Wuppertal DE ProteoSysAG,Mainz DE UniversityofVeterinaryMedicine,Hannover DE UppsalaUniversity SE Bourgas'ProfessorAssenZlatarov'University,Bourgas BG UniversityofNaturalResourcesandAppliedLifeSciences, AT Vienna UK LiverpoolJohnMooresUniversity EggCentrisNV,Zellik BE InstituteofAppliedScientificResearch(TNO),Zeist NL NationalAgencyforNewTechnologies,Energyandthe IT EnvironmentofItaly(ENEA),Rome FlemishInstituteforTechnologicalResearch(VITO),Mol BE UniversityofCopenhagen DK IT EuropeanCommission,JointResearchCentre(JRC),Ispra InVitroTestingIndustrialPlatform,TresCantos ES UniversityofKonstanz DE UniversityofFreiburg DE UniversityofEasternFinland(exUniversityofKuopio) FI UniversityofSiena IT 211 212 CONTRACTNUMBER:018681 PROJECTTYPE:Integratedproject TOTALPROJECTCOST: €14486665 ECCONTRIBUTION:€10999700 STARTINGDATE:October1,2005 ENDDATE:March31,2011 DURATION:66months SENSITIV NOVELTESTINGSTRATEGIESFORINVITRO ASSESSMENTOFALLERGENS Summary: SENSITIV was an integrated EUfunded researchprojectinvolving28partnerscoming from across Europe. They were joined together by the common goal of developing alternative strategies to animal testing for the assessment of skin and/or respiratory sensitising potential of chemicals. This includedthedevelopmentofpredictiveinvitromethods. Theprojecthas,interalia,usedinvitroandinvivogene knockout systems to uncover a pivotal role of innate immune mechanisms in the initiation of contact sensitivity. Proteomic and genomic studies designed to identify new biomarkers, which differentiate sensitisers from irritants and nonsensitisers, become highly successful during the last year of the project. A twotiered assay, consisting of the NCTC2544 keratinocyte test and the epidermal equivalent potency assay, has been developed.TheSENSITIVtoolboxisthemajordeliverableoftheproject.Itcontains the most advanced and promising assays developed within or with contribution of SENSITIV. Since, in contrast to the local lymph node assay (LLNA), lung and skin sensitisers very often are not detected by the same in vitro test system, different assay systems had to be developed for the two types of allergens. The consortium agreed to transfer the SENSITIV data bank after March 2011 to the more recent European data banks ToxBank and OpenTox. SENSITIV intends to draft a White Paper,summarisingallresultsobtainedandputintoawidercontext.SuchaWhite Paper could form the basis for an in vitro testing strategy to replace (regulatory required) in vivo testing of chemicals for allergenicity. More details on the project 7 outcomecanbefoundontheprojectwebsite includingnewsletters. Potentialcontributiontothefollowingpolicies: x x x x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) Council Directive on the approximation of the laws of the Member States relatingtocosmeticproducts(76/768/EEC) Directive2010/63/EUontheprotectionofanimalsusedforscientificpurposes Regulation (EC)1272/2008 on classification, labelling and packaging of substancesandmixtures EUfunding: x 7 'LifeSciences,GenomicsandBiotechnologyforHealth'thematicpriority www.sensitiv.eu 213 Mainresults: x SENSITIV project contribution to reduction and replacement of animal experimentation for allergen testing will be twofold: (i) First, the funding of basic research in the field of skin and respiratory sensitisation has led to significant contributions for a better understanding of the underlying cellular and molecular mechanisms; (ii) Second, on this basis SENSITIV can deliver a number of promising assays for nonanimal testing of allergenic sensitisers at variousstagesofdevelopment,themostadvancedandpromisingofwhichare part of what is termed the SENSITIV toolbox. All of these methods will be made accessible to academic and industrial researchers. Although probably none of these tests on its own will be able to replace the present regulatory need for animal testing, combinations, also with other in vitro methods, may eventuallyevensurpasstheinformativevalueoftheestablishedanimaltests; x However, none of all possible in vitro replacements for the local lymph node assay (LLNA) within or outside SENSITIV have yet gone through the rigid procedures for scientific validation and (hopefully) regulatory acceptance by national and international authorities. This will require further financial input andtimeconsumingexperimentalefforts; x Nevertheless, a number of these tests could be ready for nonregulatory use earlier, specifically when used for research purposes or inhouse in the compound discovery and development process, resulting in a significant reductionofexperimentalanimals.TheSENSITIVtoolboxwasalreadyapplied in a weightofevidence approach together with other data sources. This exercise demonstrated that SENSITIV tools can be particular useful for the purposeofregistrationundertheREACHregulationandclassificationunderthe classification, labelling and packaging (CLP) regulation. The REACH Regulation allows for such use of weightofevidence for filling certain endpoints, in accordance with Annex XI of the legislation and the corresponding ECHA guidance. Similarly, the CLP Regulation allows for weightofevidence with expertopinionaspartoftheclassificationofsubstancesandmixtures. 214 Coordinator: x NovozymesA/S,Bagsvaerd,DK(Dr.ErwinRoggen) Otherbeneficiaries: Organisation RuprechtKarlsUniversity,Heidelberg EuropeanCommission,JointResearchCentre(JRC),Ispra L'Oréal,Paris UnileverUKCentralResourcesLimited,Sharnbrook LundUniversity InstituteforResearchinBiomedicine,Bellinzona VUUniversityMedicalCentre,Amsterdam UniversityofLiverpool UniversityoftheWestofEngland,Bristol FraunhoferInstitute,Hannover UniversityofMilan FlemishInstituteforTechnologicalResearch(VITO),Mol MiltenyiBiotecGmbH,BergischGladbach IDIhospital,Rome MaxPlanckInstituteforImmunobiologyandEpigenetics, Freiburg UniversityofFlorence EuropeanCosmeticToiletryandPerfumeryAssociation(COLIPA), Brussels CosmitalSA,Marly InVitroTestingIndustrialPlatform,Rotterdam ScientificWriting&ConsultancyS.C.,Pedreguer RWTHAachenUniversity LouisPasteurUniversity,Strasbourg ProteomikaS.L.,Derio AlbertLudwigsUniversity,Freiburg UniversityofFreiburgFacultyofMedicine EuropeanConsensusPlatformon3RAlternativestoAnimal Experimentation(ECOPA),Brussels ProteomeSciencesR&DGmbH&Co.KG,Frankfurt 215 Country DE IT FR UK SE CH NL UK UK DE IT BE DE IT DE IT BE CH NL ES DE FR ES DE DE BE DE 216 CHAPTERV ProjectsFocusedonEmergingRisks CHAPTERV Projectsfocusedon emergingrisks 217 218 CONTRACTNUMBER:32731 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST: €3651500 ECCONTRIBUTION:€2600000 STARTINGDATE: November1,2006 ENDDATE:April30,2010 CELLNANOTOX CELLULARINTERACTIONANDTOXICOLOGY WITHENGINEEREDNANOPARTICLES Summary: CELLNANOTOX aimed at the development of innovative multidisciplinary sets of tests and indicatorsfortoxicologicalprofilingofnanoparticles(NPs),aswellasunravellingthe correlation between the physicochemical characteristics of NPs and their toxic potential,onvariousorgansofthehumanbody.Foracomprehensiveunderstanding of the complex data to be obtained on toxicology of NPs, based on in vitro and ex vivostudies,conventionaltoxicologywasemployedcombinedwithtoxicogenomics, metabonomics,knowledgediscoveryfromdataanddatamining.Sinceitwasshown that the penetration of NPs into the human body proceeds principally through inhalation or orally, the lung and the intestine were chosen as the primary interacting tissues/organs with NPs, while the liver, kidneyandtheimmunesystemhavebeenselectedto bethesecondary majorsites ofinteraction,following thepenetrationofNPsintothebloodcirculation.The interactionoftheNPswithtargetorganswasstudied by making use of alternative methods to animal experimentationbyemployinginvitrocellsystemsas wellasexvivostudies,basedonprecisioncutslicesofthelung,liverandkidney.The results showed that the various cellular systems showed somewhat different susceptibility towards exposure to nanoparticles, although the overall trend of the toxicological response was similar. Under the concentration range used, gold nanoparticlesshowedalmostnotoxicity,whereascobaltaggregatesofnanoparticles, cobaltferriteandquantumdotswereshowntobetoxic.Thetoxicologicalresponse depended on the cellular model as well as on the duration of exposure to the nanoparticles. One of the consequences of being exposed to nanoparticles was an oxidative stress imposed on the cells and an inflammatory response of the cells to 1 theNPs.Moredetailedresultsareavailableontheprojectwebsite . Potentialcontributiontothefollowingpolicies: x TheEuropeanstrategyfornanotechnologyandthenanotechnologyActionPlan EUfunding: x 'Nanotechnologies and nanosciences, knowledgebased multifunctional materialsandnewproductionprocessesanddevices'thematicpriority 1 www.fp6cellnanotox.net 219 Mainresults: x Nanoparticlesareinternalisedbythedifferentcellsbydifferentmethods; x The activation of the immune system was assayed and patterns of inflammatory molecules produced in response to exposure to the NPs characterised; x ToxicologicalscreeningoffourtypesofNPswascarriedout,consistingofcobalt NPs, gold NPs, cobaltferrite NPs and quantum dots, using in vitro model systemsofthelung,intestine,liver,kidneyandtheimmunesystem.GoldNPs, cobalt ferrite NPs, as well as corresponding, radioactively labelled NPs, were synthesised by the consortium. The screening was based on alveolar type II cellsandlungslicesforthelung,onCaco2cellsfortheintestine,onMDCKand HEPG2cellsforthekidneyandtheliver,respectively,andonmurineprimary dendritic cells for the immune system. Under the concentration range used, goldNPsandquantumdotswereshowntobenontoxic,whereasaggregates ofcobaltNPsandcobaltferriteNPswereshowntobetoxic; x Therewasdifferentialsensitivitytowardstoxicityofthedifferentcelllinesfor cobaltionsandcobaltNPs.Thehierarchyofcellsensitivitytowardscobaltions is:A549>MDCK>NCIH441>Caco2>HepG2>Dendriticcells,whereA549is the most sensitive cell line and primary dendritic cells are the least sensitive ones. However, a different hierarchical pattern emerged for CoNPs: A549 = MDCK=NCIH441=Caco2>Dendriticcells>HepG2; x It can be concluded that nanoparticles are taken up by different cellular systems and their internalisation depends on the properties of the particles, theparticlechemistry,andthelengthofexposuretoNPs,andonthedifferent cellularsystemsused; x ExperimentsontheoxidativestressinducedbycobaltferriteNPsinCaco2cells demonstrate that they possess reactive oxygen species (ROS)generating potential,beingabletodecreaseglutathionelevel(animportantantioxidantof the cell) and to increase intracellular ROS measured by flow cytometry using dichlorodihydrofluoresceinasanopticalprobe; x No genotoxicity and/or genomic instability in the in lymphoblastic (TK6) and Balb/3T3fibroblastscellswasfound; x Lactate,glutamineandglucosemetabolismhasbeenstudiedinboththeliver andthekidneyintheabsenceandthepresenceofthenanoparticlesofinterest. Forthelung,onlyglucoseappearedtobemetabolisedatsignificantrates.The results provide absolute values for fluxes through the key enzymes of lactate and glutamine metabolism in the rat liver and kidney and of glucose metabolismintheliver,thekidneyandthelung; x Experiments performed in the presence of carbon nanotubes (standard multiwallnanotubesof 2050m)indicatethat,forthetested concentrations, thereisnocytotoxicityandnoactivationofdendriticcells; x TheKnowledgeDiscoveryfromData(KDD)anddataminingmethodologywas applied for the analysis of the toxicity of cobalt NPs and Coferrite NPs using differentcellularmodels. 220 Coordinator: x TelAvivUniversity,FacultyofMedicine,IL(Prof.RafiKorenstein) Otherbeneficiaries: Organisation Country NationalInstituteofHealthandMedicalResearch(INSERM), FR Grenoble,Lyon EuropeanCommission,JointResearchCentre(JRC),Ispra IT UniversityofMünster,InstituteofMineralogy DE JohannesGutenbergUniversity,Mainz DE BASFSE,Ludwigshafen DE CERICOL,Sovignana IT Tp21GmbH,Saarbrücken DE 221 222 CONTRACTNUMBER:36961 PROJECTTYPE: Integratedproject TOTALPROJECTCOST: €13730066 ECCONTRIBUTION: €10000000 STARTINGDATE:April1,2007 ENDDATE:June30,2011 DURATION:51months CIRCE CLIMATECHANGEANDIMPACTRESEARCH:THE MEDITERRANEANENVIRONMENT Summary: 2 CIRCE aimedatdevelopingforthefirsttimean assessmentoftheclimatechangeimpactsinthe Mediterranean area. The objectives of the projectwereto:(i)predictandtoquantifyphysicalimpactsofclimatechangeinthe Mediterraneanarea;(ii)evaluatetheconsequencesofclimatechangeforthesociety andtheeconomyofthepopulationslocatedintheMediterraneanarea;(iii)develop anintegratedapproachtounderstandcombinedeffectsofclimatechange;and(iv) identifyadaptationandmitigationstrategiesin collaboration with regional stakeholders. The work package on human health aimed at (i) identifying and assessing selected health impacts of climate change in the Mediterranean; (ii) contributing to the Regional Climate Change assessment by estimating the potential health impacts of climatechangeinselectedMediterraneancountries;(iii)trainingepidemiologistsand healthworkersinassessingthehealthimpactsofclimatechange;and(iv)discussing with stakeholders meetings potential strategies in reducing health impacts. The results show that potential climate change impacts can be attributed to various factorssuchasexposureofhumanstoextremetemperatures,sealevelrise,flooding, drought and fires, air pollution and ozone. This can lead to important health risks including cardiovascular diseases, respiratory diseases, communicable diseases, injuries,mentalhealth,andmalnutrition. Potentialcontributiontothefollowingpolicies: x Climatepolicies x Publichealthpolicies EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 2 www.circeproject.eu 223 Mainresults(relatedtohealth): x Thescopeoftheresearchlineonhumanhealthwastoraiseawarenessthatthe manifold impacts of climate change considered in CIRCE have far reaching health implications. This includes the exposure of humans to extreme temperatures,sealevelrise,flooding,droughtandfires,airpollutionandozone and leads to important health risks (cardiovascular diseases, respiratory diseases,communicablediseases,injuries,mentalhealth,malnutrition); x The effect of temperature and air pollution as selected health impacts of climate change have been assessed in ten Mediterranean cities (Athens, Barcelona,Bari,Istanbul,Lisbon,Palermo,Rome,TelAviv,TunisandValencia); x Climate sensitive infectious diseases have been identified and the published literaturehasbeenreviewedtoestablishthecurrentstateofknowledge; x Cutaneousleishmaniasisisaseasonalvectorbornediseasehighlyinfluencedby rainfall in the previous 14 months and humidity in the environment. Inter epidemicintervalrangesfrom4to7yearsdependingoftheforceofinfection; x An integrated and validated spatiotemporal database related to zoonotic cutaneous leishmaniasis in Tunisia as a vectorborne disease demonstrator of theimpactoftheclimatechangeonhealthhasbeenbuilt; x Ageneralisedadditivemodelwasusedtostudytherelationship(assumedtobe nonlinear) between zoonotic cutaneous leishmaniasis incidence and rainfall, adjusted on potential confounders (trend, seasonality, temperature and humidity); x A generalised estimating equations (GEE) model was used to estimate the effectofhighrainfallonzoonoticcutaneousleishmaniasisincidence,adjusted onconfounders(trend,seasonalitytemperatureandhumidity); x This work contributed for the first time to demonstrate, using statistical associativemodels,theenvironmentalcharacterofcutaneousleishmaniasis,a historicalintuitiveassumptionfrequentlyreportedintheliterature.Theintra cycle seasonality as well as the interepidemic interval was formally proven, usingappropriatestatisticaltools; x Further work is required to accurately assess the effect of these climate and environmentalfactorsonwiderareasandforothervectorbornediseases; x Training material for assessing health risks of climate change has been developed and a workshop for epidemiologists, health workers and health professionalhasbeenheld; x In two countries (Malta, Turkey), full climate change and health risk assessmentshavebeenachieved. 224 Coordinator: x National Institute of Geophysics and Volcanology, Bologna, IT (Prof. Antonio Navarra) Otherbeneficiaries: Organisation Country InstituteofEarthSciences,Barcelona ES MediterraneanCentreforEnvironmentalStudies,Valencia ES CLUsrl,CastelfrancoEmilia IT DanishMeteorologicalInstitute,Copenhagen DK UniversityofCrete,Heraklion EL NationalAgencyforNewTechnologies,Energyandthe IT EnvironmentofItaly(ENEA),Rome EniEnricoMatteiFoundation,Milan IT ComplutenseUniversityofMadrid ES DE InstituteforCoastalResearch,Geesthacht InstituteofAcceleratingSystemsandApplications,Athens EL InstituteofAtmosphericSciencesandClimate,Bologna IT InstituteofBiometeorology,Florence IT WaterResearchInstitute,Bari IT PotsdamInstituteforClimateImpactResearch DE FR InternationalCentreofCooperationinAgronomicResearch forDevelopment(CIRAD),Montpellier PierreSimonLaplaceInstitute,Guyancourt FR InternationalEnvironmentandDevelopmentResearchCentre FR (CIRED),NogentsurMarne TechnicalUniversityofMadrid(UPM) ES WHOEuropeanCentreforHealthandEnvironment,Rome IT InstituteofSustainableDevelopmentandInternational FR Relations,Paris NaturalEnvironmentResearchCouncil,SwindonWiltshire UK DE MaxPlanckInstituteforBiogeochemistry,Jena MaxPlanckInstituteforMeteorology,Hamburg DE MaxPlanckInstituteforChemistry,Mainz DE NationalObservatoryofAthens EL NationalInstituteofMarineScienceandTechnology, TN Salammbo UniversityofHaifa IL AT UniversityofNaturalResourcesandAppliedLifeSciences, Vienna IT EuropeanCommission,JointResearchCentre(JRC),Ispra BarcelonaSciencePark ES RomeEnvironmentalHealthAuthority IT 225 MétéoFrance,Paris MetOffice,Exeter UniversityofTuscia,Viterbo UniversityofYork UniversityofBirmingham UniversityoftheBasqueCountry,Leioa PolytechnicUniversityofCatalonia,Barcelona NationalandKapodistrianUniversityofAthens TelAvivUniversity UniversityofAlcaládeHenares,Madrid Zadigromasrl,Rome UniversityofEastAnglia,Norwich UniversityoftheBalearicIslands,PalmadeMallorca UniversityofLisbon,FacultyofSciences UniversityofHamburg UniversityoftheAegean,Mytilene CentreforEnvironmentandDevelopmentforArabRegion andEurope,Cairo UniversityofBern UniversityofL'Aquila,Coppito FreeUniversityofBerlin UniversityofSalento,Lecce EuropeanClimateForum,Potsdam VUUniversity,Amsterdam HebrewUniversityofJerusalem UniversityofSantiagodeCompostela,Vigo EuroMediterraneanCentreforClimateChange,Lecce PasteurInstituteofTunis AssociationforResearchonClimateandEnvironment,Oran InternationalCentreforAgriculturalResearchintheDry Areas,Aleppo HellenicCentreforMarineResearch,AnavissosAttiki UniversityofSouthampton BenGurionUniversityoftheNegev,BeerSheva PaulScherrerInstitute,Villingen InstituteofCommunicationandComputerSystems,Athens NationalInstituteforOceanographyandExperimental Geophysics,SgonicoTrieste UniversityofBologna MediasFrance,Toulouse 226 FR UK IT UK UK ES ES EL IL ES IT UK ES PT DE EL EG CH IT DE IT DE NL IL ES IT TN DZ SY EL UK IL LX EL IT IT FR CONTRACTNUMBER:32131 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST: €4535199 ECCONTRIBUTION:€2793235 STARTINGDATE: November1,2006 ENDDATE:October31,2009 DURATION:36months DIPNA DEVELOPMENTOFANINTEGRATED PLATFORMFORNANOPARTICLEANALYSISTO VERIFYTHEIRPOSSIBLETOXICITYANDTHE ECOTOXICITY Summary: 3 The aim of the DIPNA project was to provide knowledge about the impact of four different nanoparticles (NPs) cobalt, gold, cerium and iron oxide on different types of cells to identify novel biomarkers andtodevelopassaysfortheevaluationofnanotoxicity.Theprojectalsodeveloped technologicalsolutionstosetupsingletNPcellinteractionswithbuiltinsensorsto evaluatetheeffects,adeviceforautomaticevaluationofthetoxicologicalimpactof NPs in work places, and a system for repeated spraying of dry NPs in the air. The results have the potential to contribute to EU policies by providing (i) recommendations for the handling of NPs in nanotechnological laboratories; (ii) reference protocols for nanotoxicity tests. Such protocols, after appropriate validation,couldbeadoptedasastandardtest;(iii)aprototypeforanautomatictest to detect the possible toxicity of NPs according to biological parameters, a nanodispensertobeusedinothernanotoxicologicaltests,andsprayersofNPsinthe air; (iv) passive and active collectors of NPs in work places; (v) software to identify andquantifyNPsinanairfilterthatcanconstitutethebasisfortheidentificationof threshold concentrations of nanopollution; (vi) a databank for occupational micro and nanopollution that can be used for traceability of human exposure; (vii) recommendations for workers’ safety in occupational settings and for nanotoxicologists. Two partners established in 2008 a startup company with the purposeofdesigning,testingandplacingonthemarketacellbasedassaythatcan beusedtoroutinelymonitorworkplacesafety.Anotherpartnerfoundedastartup companytoconstructandcommercialisetheprototypeinstrumentfortheautomatic evaluation of NP toxicity. More details on results can be found in a compendium publishedin2010. Potentialcontributiontothefollowingpolicies: x TheEuropeanstrategyfornanotechnologyandthenanotechnologyActionPlan EUfunding: x 3 'Nanotechnologies and nanosciences, knowledgebased multifunctional materialsandnewproductionprocessesanddevices'thematicpriority www.dipna.eu 227 Mainresults: x x x x x x x x NPsofdifferentcomposition(Au,Co,Fe 3 O 4 andCeO 2 ),size(from4to50nm), shape(spheres,rodsanddisks),andsurfacestate(organicorbiologicalcoatings, positive or negative surface charges) were synthesised. In addition, Ag NPs were synthesised, characterised and distributed as reference material due to theirwellknowngermicidaleffectsandtoxicityformammaliancells; CommonprotocolsweredevisedandimplementedtoverifytheimpactofNPs on different types of human immune defence cells: T cells, epithelial cells, monocytes, macrophages, and dendritic cells. NP genotoxicity and carcinogenicitywerealsoassessedinmurineBalb/3T3cells; Thereportercelllinesusingluciferaseasthereporteraresuitablefordetecting cellularstressandimmunotoxiceffectsinNPpreparations.Thereportergene assay is highly sensitive, technically easytouse, inexpensive, reproducible, robustandsuitableformediumtohighthroughputscreening; Using whole human genome transcriptomics, insight was gained into the immunerelated genes and molecular processes that are induced in the bronchialBEAS2Bcellline,alveolarA549epithelialcellline,andtheCaco2gut epithelial cell line, exposed to cobalt and cerium oxide NPs at noncytotoxic concentrations; Protocols were developed and evaluated for cell assays in miniaturised cell culturechamberstoenableasensitivedeterminationofNPthresholdscausing toxiceffectsonsinglecells; AnexposurechamberwasdevelopedtodepositairborneagglomeratesofNPs oncellcultures; A system was developed to assess the inflammatory effect of NPs on cell culturesbyquantifyingthecytokineconcentrationsintheculturesupernatant; Field analysis of nanotoxicity in industrial settings was carried out. Ten nanotechnologyindustriesallowedonsiteanalysisinworkplaces,atchimney outlets, and in their immediate surroundings. The analyses were performed usinginexpensiveNPcollectors(gravimetricsensorsbasedonadhesivecarbon discsoractiveairpumpswithNPtrappingcellulosefilters). Coordinator: x UniversityofModena,IT(Dr.AntoniettaGatti) Otherbeneficiaries: Organisation UniversityofSalzburg NationalResearchCouncil(CNR),Pisa MagnaGræciaUniversity,Catanzaro GrimmAerosolTechnikGmbh&CoKG,Ainring FlemishInstituteforTechnologicalResearch(VITO),Mol CSEMSA,Neuchatel CatalanInstituteofNanotechnology,Barcelona EuropeanCommission,JointResearchCentre(JRC),Ispra 228 Country AT IT IT DE BE CH ES IT CONTRACTNUMBER:10284 PROJECTTYPE:Integratedproject TOTALPROJECTCOST: €15371752 ECCONTRIBUTION:€11497856 STARTINGDATE: November1,2004 ENDDATE:May31,2010 DURATION:67months EDEN EMERGINGDISEASESINACHANGING EUROPEANENVIRONMENT Summary: 4 The EDEN consortium included 49 public and private research institutes from 24 countries. The ecological and geographical diversity of the project area covered all relevant European ecosystems from the ArcticCircleintheNorthtotheMediterraneanbasininthesouth,andfromPortugal in the west to the Danube delta in the east. There were also partners from Africa. Thegoaloftheprojectwastoidentify,evaluateandcatalogueEuropeanecosystems and environmental conditions linked to global change – including global warming which can influence the spatial and temporal distribution and dynamics of pathogenic agents. A coordinated European approach was adopted to provide predictive emergence and spread models including global and regional preventive, early warning, surveillance, and monitoring tools and scenarios. Such tools will have a major impact on improved EU policy development and decision making, bothfornationalorinternationalagencies.Diseaseswere selected according to the vectors and hosts involved in tickborne encephalitis, their epidemiology: haemorrhagic fever with renal syndrome (rodents), leishmaniasis (sandflies), West Nile and malaria (mosquitoes).Also,AfricansourcesofWestNileandRift Valley fever viruses were studied to improve control for the benefit of African populations,andinvestigatetheriskofintroductioninEurope.Theresultsshow,in general, that climate change alone cannot explain the upsurge or emergence of vectorbornediseasesinEurope.Thiswasdemonstratedforthecaseoftickborne encephalitis in Baltic countries and Central Europe, for which socioeconomical factors (poverty) and human behaviour are tightly related to the disease risk. In addition to research activities, the project trained a large number of PhD students and produced more than 200 scientific publications in peerreviewed journals (situation in January 2012). Parts of the activities continue in EDENext, a project th fundedbythe7 FrameworkProgrammeoftheEU. Potentialcontributiontothefollowingpolicies: x x Climatepolicies Publichealthpolicies EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 4 www.edenfp6project.net 229 Mainresults: Researchresults x Ingeneral, climatechangealone cannotexplainthe upsurge or emergenceof vectorbornediseasesinEurope.Thiswasdemonstratedforthe case oftick borne encephalitis in Baltic countries and Central Europe, for which socio economical factors (poverty) and human behaviour are tightly related to the diseaserisk; x An exception may be the effect of warmer climate on the increased risk of rodentborne diseases such as haemorrhagic fever with renal syndrome (Hantavirus infection) in Fennoscandia and Belgium. In both cases, environmental drivers are different (reduction of snow cover for the former, masting in deciduous forests for the latter), and human behaviour is the determinantfactorforexposuretotherisk; x The risk of malaria resurgence in the Mediterranean basin is very low, and climate change has virtually no influence on it. In contrast, agriculture, the management of agricultural pests, and agricultural policies play a role. However, the early detection and treatment of autochthonous cases is the most determinant factor to prevent malaria resurgence after a possible reintroductionoftheparasite; x WestNilevirus(WNV)hasestablishedinseveralEuropeanterritories,including RomaniaandSpain.Thereisnowevidencethatadultmosquitoes(Culexspp.) canensureoverwinteringoftheWNV.Thus,virusintroductionfromAfricaby migratory birds is not necessary to trigger WNV outbreaks. However, understanding and quantifying this risk, and thorough surveillance of WNV strains circulating in Europe and Africa, is of major importance to prevent or alleviatelargescaleWNVepidemics; x Considerableprogresshasbeenmadeforintegratinglowandhighresolution satellite imagery, as well as statistical and mathematical modelling, to build quantitativepredictionmodelsfortheestablishmentofvectorbornediseases. Themethodwasfirstlyusedtodevelopapredictivemodelfortheemergence of canine leishmaniasis in southern France. This model can account for both local(e.g.,landscape)andglobal(e.g.,climate)changes,andmaybeextended toothervectorbornediseasesinthefuture. Training x Attheendoftheproject,ca.60studentshaveusedEDENdataandattended workshops, training courses and PhD meetings organised during the annual consortiummeetings.Thus,theysharecommonmethodsandtools,andhavea broadviewontheimpactofenvironmentalchangesonvectorbornediseases. Many have now found postdoctoral or permanent positions, and form the basis of a European multidisciplinary research network on vectorborne diseases. Dissemination x Around 200 scientific publications have been published in peerreviewed journals(situationinJanuary2012).Anupdatedlistisavailableontheproject websiteandwillbemaintainedaftertheendoftheproject; 230 x x Ahugesetofinformationhasbeencollectedandreshapedforthepurposeof epidemiologicalstudiesconductedbythemembersoftheEDENconsortium.It includes climatic, environmental and administrative information on a wide range of spatial and temporal resolutions. These data will be used by international public health agencies such as the European Centre for Disease PreventionandControl(ECDC); An international conference on the effect of environmental changes on the emergence of vectorborne diseases was held in Montpellier in May 2010. It gathered 400 scientists from Europe and other continents. Besides a comprehensive presentation of the scientific results obtained during the project, invited keynote speakers brought their views and promoted a high levelscientificdebate.Theproceedingsareplannedtobepublishedinabook. Networkingandexpertise x TheEDENconsortiumwasmobilisedtocarryoutexpertassessmentsonbehalf ofpublichealthagencies.Thus,an“Assessmentofmagnitudeandimportance of vectorborne diseases in Europe” was conducted for ECDC, with the definitionofanactionplantoimprovethesurveillanceandcontrolofvectors and vectorborne diseases. Consecutively, a European network of entomologicalandpublichealthspecialistswasestablishedtoassistECDCinits preparednessactivitiesonvectorbornediseases:VBORNET. Coordinator: x International Centre of Cooperation in Agronomic Research for Development (CIRAD),Montpellier,FR(Dr.RenaudLancelot) Otherbeneficiaries: Organisation Country UtrechtUniversity NL CatholicUniversityofLouvain,LouvainlaNeuve BE UniversityofOxford UK EuroAEGISEuropeanAgroEnvironmentalHealthAssociates, BE Zoersel UniversityofRome'LaSapienza' IT ItalianNationalReferenceCentreforVeterinaryEpidemiology IT 'G.Caporale',Teramo InstitutPasteur,Paris FR CarlosIIIHealthInstitute,Madrid ES FR InterdepartmentalArrangementforMosquitoControlof MediterraneanCoast(EID),Montpellier InstituteofVertebrateBiology,Brno CZ ItalianNationalHealthInstitute(ISS),Rome IT InstituteforResearchandDevelopment(IRD),Montpellier FR 231 HacettepeUniversity,Ankara NewUniversityofLisbon,InstituteofTropicalHygieneand Medicine NationalInstituteofHygiene,Rabat UniversityofValencia CentreforAlpineEcology,Trento MedicalUniversityofBiaystok LudwigMaximiliansUniversity,Munich SlovakAcademyofSciences,DepartmentofMedicalZoology NationalInstituteforHealthDevelopment,Tallinn MedicalFacultyofLjubljana,InstituteofMicrobiology NeikerTecnalia,theBasqueInstituteforAgriculturalResearch andDevelopment,Derio “JohanBéla”NationalCentreforEpidemiology,Budapest PublicHealthAgency,Riga CentreforCommunicableDiseasesPreventionandControl, Vilnius FinnishForestResearchInstitute,Vantaa FrenchNationalInstituteforAgriculturalResearch(INRA), MontferriersurLez SwedishInstituteforInfectiousDiseaseControl,Solna UniversityofAntwerp UniversityofHelsinki UniversityofLiverpool NaturalHistoryMuseum,London EgeUniversityMedicalSchool,BornovaIzmir LondonSchoolofHygieneandTropicalMedicine SzentIstvanUniversity,Budapest UniversityofBarcelona UniversityofMontpellierI UniversityofCrete,Heraklion HassanIIAgroveterninaryInstitute,Rabat SenegaleseInstituteofAgriculturalResearch,Dakar NationalInstituteofResearchandDevelopmentfor MicrobiologyandImmunology"Cantacuzino",Bucarest DanubeDeltaNationalInstituteforResearch,TulceaCounty NationalResearchCouncil(CSIC),Sevilla PasteurInstitute,Alger HungarianAcademyofSciences,DepartmentofViralVaccines andPathogenesis,Budapest PasteurInstitute,Dakar AviaGis,Zoersel TR PT MR ES IT PL DE SK EE SI ES HU LV LT FI SE BE FI UK UK TR UK HU ES FR EL MR SN RO RO ES DZ HU SN BE 232 CONTRACTNUMBER:505539 PROJECTTYPE:Integratedproject TOTALPROJECTCOST:€22793 436 ECCONTRIBUTION:€15000000 STARTINGDATE:September1, 2004 ENDDATE:December31,2009 DURATION:64months ENSEMBLES ENSEMBLEBASEDPREDICTIONSOFCLIMATE CHANGESANDTHEIRIMPACTS Summary: The ENSEMBLES consortium was composed of 66 institutes from 20 countries. The principal objective of the project was to measure uncertainties in climateprojectionssothataclearerpictureoffuture climate can be formed. One specific aim was to maximisetheexploitationoftheresultsbylinkingthe outputsoftheensemblepredictionsystemtoarange ofapplications,includingagriculture,health,foodsecurity,energy,waterresources, insurance and weather risk management. Among the many impacts of climate change,thoseonhealthareparticularlyimportantfortheirimmediateandobvious relevance to human wellbeing, but also because of their implications for health expenditures and for the productivity of the labour force. For these reasons, dedicatedresearchwasdevotedtotheinvestigationofthistopicwithintheproject. The results showed, among others, that climate change can affect human health throughawiderangeofmechanismsandforarangeofdiseasesorhealthoutcomes (deaths, injuries). The adverse impacts on health will outweigh the benefits. Furthermore,themethodsforestimatingthehealtheffectsofclimatechangeareat anearlystageofdevelopment.Detailsontheprojectoutcomecanbefoundinthe 5 finalreportavailableontheprojectwebsite . Potentialcontributiontothefollowingpolicies: x x Climatepolicies Publichealthpolicies EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 5 www.ensembleseu.org 233 Mainresults(relatedtohealth): x Climatechangecanaffecthumanhealththroughawiderangeofmechanisms andforarangeofdiseasesorhealthoutcomes(deaths,injuries); x The impacts on health will outweigh the benefits, and populations in low incomecountriesarelikelytobeworstaffected; x Methods for estimating the health effects of climate change are at an early stageofdevelopment.Inappropriateassumptionshaveoftenbeenincludedin integratedassessmentmodelswithrespecttohealthoutcomesandthereisa needtoimprovetherelevanthealthimpactmodels; x Future disease burdens are sensitive to the underlying assumptions about populationgrowthandageing,andfuturehealthstatus; x Global climate change will increase outdoor and indoor heat loads, and may impair health and productivity for millions of working people. A model was developed that applies physiological evidence about effects of heat, climate guidelines for safe work environments, climate modelling, and global distributions of working populations to estimate the impact of climate scenariosonfuturelabourproductivity; x Empiricalstatistical models were developed to estimate the direct impact of daily temperature on respiratory and cardiovascular mortality (the direct effects of heat and cold) and on diarrhoeal disease mortality, based on observationalstudiesofexposureresponsefunctions; x Climatevariability,ascharacterisedbyextremeweathereventsandinterannual variability,isknowntoaffectcertain infectiousdiseases.Theimpacts oflong term shifts in climate conditions may lead to shifts in the distribution of infectiousdiseasesandareassuitableforfoodproduction; x Although the interactions involved can be numerous, complex and subtle, climatedeterminesthepotentialofmanyinfectiousdiseasestoflourish.Onthe otherhand,healthcareinfluencestheactualincidenceofdiseases.Onewould therefore expect that, in a scenario of economic growth, infectious diseases would fall as health care improves. Likewise, in a scenario of global warming, one would expect to see infectious diseases spread into new regions and perhapsintensify.Itisthusextremelyimportantandscientificallychallengingto assess the impacts on mortality in a scenario with both climate change and economicdevelopment; x This assessment has been performed for subSaharan Africa. Scenarios for threedeterminantsofdevelopment–percapitaincome,literacy,andabsolute poverty – and for climate change have been used to project the future incidenceofmalaria,assumingthatitchangesinproportiontoinfantmortality. Itwasshownthatdeathsfrommalariawillfirstincrease,becauseofpopulation growth and climate change, but will then fall, because of development. This patternisrobusttothechoiceofscenario,parameters,andstartingconditions; and also holdsfor diarrhoea, schistosomiasis and dengue fever. However, the timingandlevelofthemortalitypeakisverysensitivetoassumptions. 234 Coordinator: x MetOfficeHadleyCentre,Exeter,UK(Dr.JohnMitchell) Otherbeneficiaries: Organisation MétéoFrance,Paris PierreSimonLaplaceInstitute,Paris DanishMeteorologicalInstitute,Copenhagen EuropeanCentreforMediumRangeWeatherForecasts,Reading InternationalInstituteforAppliedSystemsAnalysis,Laxenburg ItalianNationalInstituteofGeophysicsandVolcanology, Bologna RoyalNetherlandsMeteorologicalInstitute,DeBilt UniversityofBristol MaxPlanckInstituteforMeteorology,Hamburg NationalObservatoryofAthens SwedishMeteorologicalandHydrologicalInstitute,Norrköping UniversityofEastAnglia,Norwich UniversityofFribourg UniversityofHamburg UniversityofReading RegionalEnvironmentalProtectionAgencyforEmiliaRomagna (ARPA),Bologna AristotleUniversity,Thessaloniki BureauofMeteorologyResearchCentre,Melbourne CERFACS,Toulouse CzechHydrometeorologicalInstitute,Prague CenterforInternationalClimateandEnvironmentalResearch, Oslo Climpact,Paris InstituteofAtmosphericSciencesandClimate,Bologna CharlesUniversity,Prague UniversityofFlorence,DepartmentofAgronomyandLand Management GermanWeatherService,Hamburg ElectricitédeFrance(EDF),Chatou EcoleNormaleSupérieure(ENS),Paris SwissFederalInstituteofTechnology,Zürich EniEnricoMatteiFoundation,Milan FoundationforClimateResearch,Madrid FinnishMeteorologicalInstitute,Helsinki UniversityofAppliedSciences,Stuttgart FreeUniversityofBerlin InstituteforCoastalResearch,Geesthacht 235 Country FR FR DK UK AT IT NL UK DE EL SE UK CH DE UK IT EL AU FR CZ NO FR IT CZ IT DE FR FR CH IT ES FI DE DE DE InstituteofAtmosphericPhysics,Prague AbdusSalamInternationalCentreforTheoreticalPhysics,Trieste SpanishNationalInstituteofMeteorology,Madrid ColumbiaUniversity,NewYork UniversityofStuttgart EuropeanCommission,JointResearchCentre(JRC),Ispra LondonSchoolofEconomics LondonSchoolofHygieneandTropicalMedicine NorwegianMeteorologicalInstitute,Oslo SwissFederalOfficeofMeteorologyandClimatology,Zürich NansenEnvironmentalandRemoteSensingCentre,Bergen NationalInstituteofHydrologyandWaterManagement, Bucharest NationalMeteorologicalAdministration,Bucharest ResearchCentreforAgriculturalandForestEnvironment, Poznan PotsdamInstituteforClimateImpactResearch SMASH,Paris FinnishEnvironmentInstitute,Helsinki UniversityofCantabria,Santander CatholicUniversityofLouvain,LouvainlaNeuve UniversityofCastillaLaMancha,Toledo UniversityofOslo LundUniversity UniversityofKassel UniversityofLiverpool UniversityofOxford University'JosephFourier'Grenoble1 MetEireann(CommunityClimateChangeConsortiumfor Ireland),Dublin UniversityofBern LeibnizInstituteofMarineSciences,Kiel UniversityofGeneva NetherlandsEnvironmentalAssessmentAgency,Bilthoven AarhusUniversity 236 CZ IT ES US DE IT UK UK NO CH NO RO RO PL DE FR FI ES BE ES NO SE DE UK UK FR IE CH DE CH NL DK CONTRACTNUMBER:36306 PROJECTTYPE:Specific targetedresearchproject TOTALPROJECTCOST: €2908065 ECCONTRIBUTION:€2400000 STARTINGDATE: October1,2006 ENDDATE:March31,2010 DURATION:42months HEALTHYWATER ASSESSMENTOFHUMANHEALTHIMPACTSFROM EMERGINGMICROBIALPATHOGENSINDRINKING WATERBYMOLECULARANDEPIDEMIOLOGICAL STUDIES Summary: 6 Theoverallgoaloftheproject wastoadvancethe knowledge on pathogenesis of emergent microbial pathogens in drinking water to understand their transmissiontohumans.Theprojectfocusedonall majortypesofpathogens,i.e.,viruses,bacteriaand protozoa,andconcentratedonarepresentativeset ofEuropeandrinkingwatersupplysystemsandsourcewatersofspecificsensitivity to human health. To reach the overall goal, the following detailed objectives were set: (i) Validation and application of detection technologies for emerging microbial pathogens based on nucleic acids; (ii) Molecular survey and comparative detailed study of emerging pathogens in European drinking water sources and supply systems; (iii) Understanding the human health impact of emerging pathogens by primary epidemiological studies targeted at specific systems and pathogens; (iv) Determination of epidemiological correlations with molecular and environmental data and assessment of risk for waterborne microbial infections in Europe. An integratedresearchapproachwaspursuedtoachievetheseobjectivesbycombining molecular and classical detection, activity assessment and epidemiological understanding of emerging pathogens in a specific set of drinking water systems from different European regions. The project generated validated detection technologiesforthetargetedwaterbornepathogensandrevealedpossibleroutesof transmission to humans via drinking water consumption. This new knowledge provides guidance to improve the quality of European drinking water supplies and reducetheburdenofwaterborneinfectionsforEuropeanpopulations. Potentialcontributiontothefollowingpolicies: x Council directive (98/83/EC) on the quality of water intended for human consumption EUfunding: x 'Foodqualityandsafety'thematicpriority 6 www.helmholtzhzi.de/en/healthy_water 237 Mainresults: Developmentandvalidationofmoleculardetectiontechnologies x 2036samplesweretakenoriginatingfromSpain,Germany,France,theUnited Kingdom and Hungary and covering raw water, finished drinking water, semi treateddrinkingwaterandsamplesfromwaterstoragetanks,wereprocessed fordirectmicroscopy,culturemethodsordifferenttypesofmolecularmethods. Concentration technology was applied separately for viruses, bacteria and protozoa, because they are too different to have a single concentration procedure; x Primers and probes for most targeted pathogenic bacteria, viruses and protozoa were validated. The primer sets for Legionella and Helicobacter, includingL.pneumophila,andH.pylori,weretestedonalargesetofdrinking watersamplesfromSpainandGermany; x For bacteria, genusspecific singlestrand conformation polymorphism (SSCP) fingerprints were used to analyse the prevalence of Helicobacter spp. and Legionella spp. Most of the screened samples from Spain and Germany contained Legionella species, whereas for Helicobacter species only samples fromSpain(theLlobregatriversystem)werepositive. Molecularsurveyandcomparativedetailedstudy x In general, all water supply stations studied, except the most upstream river station, showed contamination with pathogenic viruses, mostly noroviruses TypeIandII,Sapoviruses,and,inonecase,hepatitisAvirus; x Substantial differences in the bacterial community structure were observed betweenwinterandlatesummer; x Analysis of the smallscale network connected to the local drinking water supply system of the city of Braunschweig (DE) showed that there were pronounced differences between the species composition of bulk water and biofilms. Understandinghumanhealthimpactsofemergingpathogens x Virion capsid integrity of chlorinetreated viruses was tested for human astroviruses and noroviruses. A decrease in the infectivity of astroviruses, a representativeentericvirus,positivelycorrelatedwiththeamountofoxidative damageofvirusparticles; x When human norovirus was treated with chlorine, virions could also be recovered as oxidatively damaged particles. Therefore, the detection of carbonylated viralparticlescouldbeapowerfultool fortheevaluationofthe decreaseintheinfectivityofnonculturableviruses; x Genes associated with virulence were analysed in bacterial isolates, including Legionella pneumophila (mip), Campylobacter jejuni and Campylobacter coli (cdt, fla), and Escherichia coli O157 (stx1, stx2). Acrobacter and Aeromonas, considered as emerging waterborne pathogens, were obtained and screened forseveralvirulencefactors,suchasstx1andstx2; 238 x Substantialprogresswasobtainedintheunderstandingoftheimpactofstrain variationofvirulencefactorsforprotozoalpathogenssuchasCryptosporidium spp.inEurope. Determinationofepidemiologicalcorrelations x A diary study for private water supply consumers was completed to estimate thediseaseburdenfromdrinkingwater.268householdswererecruitedinthe UK.Watersampleswerecollectedandanalysedforindicatorbacteria; x Results of a UK telephone survey were used to estimate the disease burden associatedwithpressurelosseventsandthediarrhoeariskrelatedtodistance fromwatertreatmentworks; x For tracking sources of contaminations, foecal samples were taken from aquaticbirdsonselectedareasinHungaryandthepresenceofCryptosporidium species and Giardia duodenalis determined. The results indicate that aquatic ducks, geese, coot and cormorant can play role in the environmental disseminationofhumanpathogenicGiardiacystsandCryptosporidiumoocysts inHungary. Recommendationfordrinkingwatersafety x Standardisededucationaboutthehealthrisksofconsumptionofcontaminated waterfromsmallruralsuppliesisveryimportant; x Increasingthefrequencyofcontactwithconsumersisrecommended; x The Water Safety Plans (WSP) are considered a key element in the managementofdrinkingwatersystems;however,smallwaterindustriesseeit asaadditionalloadofworkandrequiretrainingonitsprinciplesandbenefits; x Examination of water by microscopy should be considered an excellent complementarymethodbesideschemicalandbacteriologicalparametersandis veryusefulincombinationwiththeWSP; x For the molecular determination of the specific pathogen load of source and drinking water, highly standardised methods are essential, validated with certifiedmolecularreferencematerialintherespectivewater; x Molecular techniques should be used to complement classical indicators to obtain a detailed understanding of the pathogen load, the infectivity and the singlebacterialstrainsresponsibleforoutbreaksofwaterborneinfectionsfrom drinkingwater. 239 Coordinator: x HelmholtzCentreforInfectionResearch,Braunschweig(Dr.ManfredHöfle) Otherbeneficiaries: Organisation Country UniversityofEastAnglia,Norwich UK InternationalAssociationforDanubeResearch,Vienna AT Rovira&VirgiliUniversity,Reus ES UniversityofBarcelona ES SUEZEnvironement,LePecq FR NationalInstituteofEnvironmentalHealth,Budapest HU UniversityofNiceSophiaAntipolis,Nice FR MolecularDiagnosticsCenter,Orihuela ES 240 CONTRACTNUMBER:36224 PROJECTTYPE:Specific targetedresearchproject TOTALPROJECTCOST: €3715600 ECCONTRIBUTION:€3469736 STARTINGDATE: November1,2006 ENDDATE:August31,2010 DURATION:46months HIWATE HEALTHIMPACTSOFLONGTERMEXPOSURETO DISINFECTIONBYPRODUCTSINDRINKINGWATER Summary: Theoverallaimwastoinvestigatepotentialhuman health risks associated with longterm exposure to low levels of disinfectants (such as chlorine) and disinfectantbyproducts(DBPs)occurringinwaterforhumanconsumptionanduse in the food industry. The study made use of existing studies/databases and newly collected information. Among the specific objectives were: (i) the determination of the DBP composition and levels in drinking waterinvariousregionsinEurope(ES,UK,LT, FR, IT, EL); (ii) identification of the determinants of DBPs and development of predictivemodels;(iii)assessmentoftherisk of reproductive effects in relation to disinfection practices and levels of DBPs; (iv) assessment of the risk of bladder and colon cancer; (v) conduction of riskbenefit analyses including quantitative assessments of risk associated with microbial contamination of drinking water versus chemical risk, comparison of alternative treatment options, and production of burden of disease estimates; (vi) review of waterdisinfectioninEuropeandworldwide;(vii)assessmentofthewaterandhealth policy implications of current disinfection practices, taking into account recent environmental,toxicologicalandepidemiologicalfindingsandthefindingsofthethis study.Theresultsshow,interalia,thattherearevariationsinDBPconcentrationsin Europe. Trihalomethane concentrations were not associated with reproductive outcomes.Thereseemstobeanexposureresponserelationshipbetweenexposure toTHMsandbladdercancerinmenbutnotwithcoloncancer.Basedontheresults, the consortium provided a number of recommendations for stakeholders. More 7 detailsareavailableontheprojectwebsite . Potentialcontributiontothefollowingpolicies: x x x x EU water policies such as Council directive 98/83/EC on the quality of water intendedforhumanconsumptionandCouncilDirective91/271/EECconcerning urbanwastewatertreatment CommunityStrategyforEndocrineDisruptersCOM(1999)706final Regulation (EC) no 1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Foodqualityandsafety'thematicpriority 7 www.hiwate.eu 241 Mainresults: x x x x x x x x x x Therewassubstantialvariationintrihalomethane(THM)concentrationsacross thestudyregions,withverylowlevelsinLithuaniaandCrete,andhighlevels, well above the current guidelines of 100 g/l, in the Barcelona (ES) area. MediumlevelswerefoundinFranceandtheUK.WithinSpain,mediumlevels were also measured in Asturias and Valencia and low levels in the Basque Country; Haloacetic acid (HAA) concentrations followed a similar pattern to the THMs, butactuallevelswerelower;chloropicrinwasonlyobservedinafewsamples; very low levels of haloketones were detected in samples from the UK and Spain; Concentrations of chloral hydrate were detected with the highest concentrationsinSpain,andlowconcentrationsintherestofSpain,Franceand theUK.ChloriteandchloratelevelswerefairlyhighattimesinItaly,becauseof theuseofchlorinedioxideastreatment; 3Chloro4(dichloromethyl)5hydroxy2(5H)furanone) levels were generally low, but noticeably higher in Bradford (UK) compared to the other study regions; Little evidence was found of any effects of THMs on reproductive outcomes includingsemenquality,congenitalanomalies,stillbirth,pretermdelivery,and birth weight. There was little evidence for geneenvironment interaction for THMsandpretermdeliveryandbirthweight.However,therewerestatistically significant associations between exposure to chlorite and chlorate and a number of congenital anomalies in Italy, but the number of cases were relatively small and there were generally no monotonic exposureresponse relationships; The pooled analyses of bladder cancer showed an exposureresponse relationshipbetweenexposuretoTHMsandbladdercancerinmen(OR=1.32; 95%CI1.01to1.71foraveragelevelofTHM4>50g/L),buttherelationship appearedlesssteepthanthatobservedinNorthAmericanstudies; TherewaslittleevidenceforarelationshipbetweenTHMsandcoloncancer; The comparative risk assessment framework that was developed allowed for therisksfromchemicalandmicrobialagentsassociatedwithdrinkingwaterto becomparedinastructuredandtransparentway; The review of the best available technologies suggested that the first step in reducing DBP formation is to use the best available source(s), which in preferentialorderare:groundwater,surfacewatersubjecttosoilpassagesuch asbankfiltration,andsurfacewatersources; Basedonthefindings,theconsortiumrecommendsthat,basedonthecurrent healthevidenceforbladdercancerandbirthweight:(i)thecurrentguidelines forDBPsindrinkingwatershouldbereviewed;(ii)astrongereffortshouldbe made to obtain information on DPBs levels and profiles in tap water in all regionsinEurope,andotherpathwaysthandrinkingwater,suchasinindustrial and food processes, where little information exists; (iii) routinely collected informationonDBPsandtheirdeterminantsshouldbemadepubliclyavailable 242 and easily accessible; (iv) health evidence database for many DBPs should be expanded, specifically for DBPs other than THMs and HAAs, such as chlorine dioxide, outcomes not included in this work, and the possible biological mechanisms;(v)watertreatmentplantsshouldlowertheirDBPlevelsasfaras possible without compromising the effectiveness of the disinfection, e.g., through source water selection and use of appropriate technologies; (vi) evidencebasedriskassessmentmethodsandtoolsshouldbeusedtoestimate thepotentialhealthimpactsofwatertreatment;(vii)possiblehealthimpactof climatechangeshouldbefurtherassessed. Coordinator: x ImperialCollegeofScience,TechnologyandMedicine,London,UK(Prof.Mark Nieuwenhuijsen) Otherbeneficiaries: Organisation Country UniversityoftheAegean,Mytilene EL NationalInstituteforHealthandWelfare(THL),Helsinki, FI Kuopio VytautasMagnusUniversity,Kaunas LT UniversityofCrete,Heraklion EL UniversityofRennes FR MunicipalInstituteofMedicalResearch(IMIM),Barcelona ES CentreforGenomicRegulation,Barcelona ES UniversityofModenaandReggioEmilia IT IT InstituteofPharmacologicalResearchMarioNegri,Milan SwedishInstituteforInfectiousDiseaseControl,Solna SE HylobatesConsultingSrl,Rome IT ICConsultantsLtd,London UK Scarab,Stockholm SE ResearchCentreforResearchinEnvironmentalEpidemiology ES (CREAL),Barcelona CatalanInstituteofOncology,Barcelona ES 243 244 CONTRACTNUMBER:13968 PROJECTTYPE: Coordinationaction TOTALPROJECTCOST:€699913 ECCONTRIBUTION:€699913 STARTINGDATE: February1,2005 ENDDATE:October31,2008 DURATION:45months IMPART IMPROVINGTHEUNDERSTANDINGOFTHE IMPACTOFNANOPARTICLESONHUMAN HEALTHANDTHEENVIRONMENT Summary: Theprimaryaimof the IMPART co ordination action was to prevent the knowledge of the health and environmental implications of nanoparticles fromlaggingbehindthetechnologicaladvances.Inorder to do this, IMPART fostered communication links betweenanumberofregional,nationaland international initiativesinordertoreduceduplicationsofeffort,topoolexpertiseandtofacilitate cooperation between networks. This resulted in an improvement in the understanding of the potential impact of nanoparticles on human health and the environment. The specific scientific and technological objectives were to: (i) co ordinatetheeffortsofregional,nationalandinternationalinitiativesrepresentedin the consortium; (ii) create and enhance good communication and permanent links betweenthepartners;(iii)carryoutareviewofthelatestscientificandtechnological developmentsrelatedtotherisksofnanoparticleexposureonhumanhealthandthe environment;(iv)disseminatetheprojectresultsthroughaspecialisedwebsiteand knowledgetransferworkshops;(v)makerecommendationstomajorfundingbodies for the future research directions in the field; (vi) produce guidelines and recommendationsfortheinstitutionoffuturenanoparticlestandardsandexposure limits.ThefinalresultsareavailableinaPowerpointpresentation. Potentialcontributiontothefollowingpolicies: x TheEuropeanstrategyfornanotechnologyandthenanotechnologyActionPlan x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Nanotechnologies and nanosciences, knowledgebased multifunctional materialsandnewproductionprocessesanddevices'thematicpriority 245 Mainresults: x Expertgroupleaderswereappointedduringthekickoffmeetingoftheproject. Members were divided into four subareas: materials for consideration; implicationsforhumanhealthandexposure;impactontheenvironment;and resultinglegislativemeasures; x Many reports were produced, including (i) The publicly available report 'Working report on the status quo of nanomaterials impact on health and environment';(ii)'Assessmentofexistingandidentificationofmissingdata'(not publicly available); 'Existing legislation applicable to nanomaterials'; 'Toxicology' (not publicly available); 'Assessment of Risks'; (not publicly available); 'Best Practices' (not publicly available); 'Recommendations and guidelines for legislation policy makers'; 'Recommendations and guidelines for researchpolicymakers';'Guidancebookletonsafehandlingofnanoparticlesfor industry,publicandotherstakeholders'; x The publically available report can be downloaded from www.temas.ch/IMPART/IMPARTProj.nsf. Nonpublically available reports, for specialneeds,mayberetrievedfromthecoordinator:[email protected]; x Themainrecommendationsforpolicymakersarethefollowing:Policymakers should(i)bepreparedtoadoptandimplementseveralimmediatemeasures,if morestudiesclearlyshowthatengineerednanoparticlesareharmfulforsafety andhealthofhumansandtheenvironment;(ii)fosterthedevelopmentofnew testingmethods(especiallytoxicologicaltesting)inordertoevaluatethesafety and health risks of engineered nanoparticles; (iii) create new protection measures at the workplace for the people that manipulate nanomaterials. Immediate protection measures recommended by the consortium to be adapted include the substitution options for nanomaterials, technical and organisational protection measures. Specific longterm regulation on nanotechnology seems technically problematic and politically improbable at themoment.Itisnecessarytomakeaconsistentuseofexistinglegislation,as longasthiscanbeeasilyappliedassuchorsuitablyamended; x The main recommendations for researchers are the following: A. Immediate measures:(i)Develop,distributeandusemanufacturedreferenceNPmaterials for toxicology studies (complete and accurate particle characterisation); (ii) DevelopreferenceNPwithlowoxidativepotential;(iii)Developstandardised, validated protocols for toxicity testing (attention to the parameters, systems, cellular components); (iv) Develop models for predicting the potential impact on health and environment; (v) Develop systems for evaluating the impact of engineered NP over their entire life. B. Longterm measures: (i) Set up mandatory registration and health–screening of all workers dealing with bulk quantitiesofengineeredNP;(ii)Setuplongtermcohortstudiestofollowtheir healthstatus;(iii)Establishabiobankforbiomaterialsfromthesecohorts;(iv) Establishafund/departmenttocoordinatetheselongtermactivities. 246 Coordinator: x TemasAgTechnologyandManagementServices,Arbon,CH(Dr.JürgenHöck)* Otherbeneficiaries: Organisation Country BioMaDeTechnologyFoundation,Groningen NL JožefStefanInstitute,Ljubljana SI NanoPowdersIndustries(Israel)Ltd.,Caesarea IL UniversityofCrete,Heraklion EL HelsinkiUniversityofTechnology FI DublinInstituteofTechnology IE CatholicUniversityofLeuven BE NationalInstituteofResearchandDevelopmentforTechnical RO Physics,Iasi UK UniversityofSurrey,Guildford NoferInstituteofOccupationalMedicine,ód PL SwissFederalLaboratoriesforMaterialsTestingand CH Research,StGallen KaunasUniversityofTechnology LT VDITechnologiezentrumGmbH,Düsseldorf DE UniversityofManchester UK InstituteofPhysicalChemistryI.G.Murgulescu,Bucharest RO LatvianSocietyofToxicology,Riga LV UniversityofCraiova RO BG BulgarianAcademyofScience,Sofia *Aftersuspensionandrestartoftheproject 247 248 CONTRACTNUMBER:36877 PROJECTTYPE: Integratedproject TOTALPROJECTCOST: €5599044 ECCONTRIBUTION:€5000000 STARTINGDATE: February1,2007 ENDDATE:January31,2011 DURATION:48months MICRODIS INTEGRATEDHEALTH,SOCIALANDECONOMIC IMPACTSOFEXTREMEEVENTS:EVIDENCE, METHODSANDTOOLS Summary: The broad objectives were to (i) strengthen the scientific foundation of the relationship between extreme events and their health, social, and economic impacts; (ii) develop and integrate concepts, method, tools and databases towards a common global approach; (iii) improve human resources and coping capacity in Asia and Europe though training andknowledgesharing.Theconsortiumrepresentedthefullspectrumofexpertsin health(e.g.,specialistsinepidemiology,disasterhealthmanagement,tropicalhealth and hygiene, public health, health system analysis), social science (sociology, social andmedicalanthropology,genderstudies),andeconomics.Attheendoftheproject, all site survey and annex studies in many locations in the EU and Asia, with the production of a number of summary reports, were completed. Partners completed designs, protocols, survey reports, preliminary analysis and submittedcleanedandvalidateddatasetsforeachstudy.Amoredetailedpolicybrief persurveycountryhasalsobeencompleted,alongwithacombinedliteraturereview onsocial,healthandeconomicimpactsofdisasters.Anotherimportantpublication was“PublicHealthandFloodsinEurope”,providingdescriptiveanalysisandmapping of various health impacts of floods across Europe and specific MICRODIS European countries.Partnersalsosharedtheirresultsandknowledgeatanumberofdifferent international conferences, workshops, visiting lectures and training events. More 8 detailsonresultsareavailableontheprojectwebsite . Potentialcontributiontothefollowingpolicies: x International strategy for disaster reduction – Hyogo Framework for action 20052015 x ACommunityapproachonthepreventionofnaturalandmanmadedisasters [COM(2009)82final] x EU strategy for supporting disaster risk reduction in developing countries [COM(2009)84final] x Directive2007/60/EContheassessmentandmanagementoffloodrisks x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 8 www.microdiseu.be 249 Mainresults: x During the first year, thematic groups worked together to develop draft literaturereviewsforsocial,healthandeconomicimpactsofnaturaldisasters. Conceptual models for each thematic group were also developed, along with continueddiscussionsaboutintegrationstrategiesandsurveymethodologies; x Thesecondyearoftheprojectputmanyoftheconceptualtoolsdevelopedin the first year into practical application. Through various meetings and workshops, the consortium developed the integrated protocol with a social, healthandeconomiccoresectiontobeusedinallsites.Theseprotocolswere then adapted to the specific country and site context. Meanwhile, intense survey designs were put into place for 8 different studies in Indonesia, India, Vietnam,PhilippinesandtheUK; x Threemainstudiesandthreeannexstudieswereheldinthecourseofthethird year. Integrated questionnaires were administered and qualitative research was done for main studies in Morpeth (UK), and Hanoi and Quang nam, (Vietnam). In addition, studies were conducted in India on the nutrition of children under five after floods in Bahraich and Orissa, respectively. The first annex study dedicated to economic impacts after floods in Quang nam, Vietnam,wasperformed.Partnersperformedtrainingandawarenessactivities insurveycommunities,institutionsandresearchcommunity; x Thelastyearsawthecompletionofallsitesurveyandannexstudies.Thefield work included two main surveys in L’Aquila (IT) andGosaba (India). Six annex studieswerealsoconducted(TwoannexstudiesinHanoiondenguefeverand floodsandonchemicalcontaminationduetofloods;onlivelihoodimpactafter cyclone Aila in West Bengal, India; health and safety risks and their management in different international disasters assessed by rescue workers, military officers and police officers in Finland; continuation on the health impactsofthePadangearthquakeinIndonesiaaswellasfortheearthquakein Sichuan,China.AsecondintegratedstudywasconductedinOrissa,India,and an annex study focused on emergency assistance and rehabilitation efforts after disasters in Southern Leyte and in the Philippines. Finally, many efforts weremadeonadditionalstudiesontheimpactsoffloodsinbothMorpethand TewkesburyintheUK; x Statistical briefs along with attractive onepage briefs for each site have been developedanddisseminatedonthewebsiteandduringimportantevents; x Amoredetailedpolicybriefpersurveycountryhasalsobeencompleted,along with a combined literature review on social, health and economic impacts of disasters; x A publication entitled “Public Health and Floods in Europe”, providing a descriptive analysis and mapping of various health impacts of floods across EuropeandspecificMICRODISEuropeancountries,wasproduced; x Two important regional symposia took place in the fourth year that provided publicity and knowledge sharing for the MICRODIS consortium and disaster researchcommunity:inHue,Vietnam,andinNewcastleuponTyne,UK. 250 Coordinator: x Centre for Research on the Epidemiology of Disasters, Catholic University of Louvain,Brussels,BE(Prof.DebaratiGuhaSapir) Otherbeneficiaries: Organisation Country UniversityofGreenwich UK UniversityofNorthumbria,Newcastle UK FinnishInstituteofOccupationalHealth,Helsinki FI JadavpurUniversity,Calcutta IN UniversityofDelhi,NewDelhi IN UniversityofIndonesia,Depok ID XavierUniversity,CagayanDeOroCity PH EvaplanGMBH,Heidelberg DE VoluntaryHealthAssociationofIndia,NewDelhi IN PH Citizens'DisasterResponseCenterFoundation,QuezonCity HealthnetInternationalFoundation,Amsterdam NL FerurbatSARL,Clamart FR HueUniversity,HueCity VT UniversityofFlorence IT SwecoGrønerAs,Oslo NO UniversityHospitalHeidelberg DE HanoiSchoolofPublicHealth VT US UnitedNationsOfficefortheCoordinationofHumanitarian Affairs,NewYork 251 252 CONTRACTNUMBER:33231 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST: €4616544 ECCONTRIBUTION:€3300000 STARTINGDATE:Janary1,2007 ENDDATE:December31,2009 DURATION:36months NANOINTERACT DEVELOPMENTOFAPLATFORMAND TOOLKITFORUNDERSTANDING INTERACTIONSBETWEENNANOPARTICLES ANDTHELIVINGWORLD Summary: 9 TheoverarchingobjectiveofNANOINTERACT was to create a firm scientific and technical basis for understanding and potentially predicting the likely biological impacts of engineered nanoscale particulates interacting with living systems. NANOINTERACT was built around the belief that a fundamental understanding of the space and timeresolved interaction of nanoparticlesintheirinsitubiologicalcontext(i.e.,withtheircoronaofproteinsand otherbiomolecules)withlivingsystemsisessential to ensure the safe implementation of nanotechnologies. The project lead to no newly identified hazard (solely due to nanoscale elements) for nanoparticles. However, it hashighlightedseveralissuesrequiringfurtherinvestigation,inparticularrelatedto the need for consideration of appropriateness of several of the established OECD (theOrganisationforEconomicCooperationandDevelopment)andothertestsfor chemicaltoxicitytoassessmentofnanoparticletoxicity.Italsounderlinedimportant issues such as the lack of comparability across data generated using different standard (e.g., OECD) test media, which have different ionic strengths and pH, different sources of serum and treatments of the serum. This is in addition to the particlerelated challenges such as the different surface properties for the same materialmadebydifferentsynthesisroutes,nottomentionissuessuchasbatchto batch reproducibility for a single nanoparticle synthesis route. More details on resultsareavailableintheEuropeanNanoSafetyClusterCompendium2010. Potentialcontributiontothefollowingpolicies: x TheEuropeanstrategyfornanotechnologyandthenanotechnologyActionPlan x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Nanotechnologies and nanosciences, knowledgebased multifunctional materialsandnewproductionprocessesanddevices'thematicpriority 9 www.nanointeract.net 253 Mainresults: x AkeyaspectoftheNANOINTERACTprojectwastheuseofinternalroundrobin typeapproaches,wherebyimportantresultsarereproducedandreplicatedin at least one completely separate laboratory using the identical protocols and startingmaterials,inordertoensurethattheresultsarescientificallyvalidand reproducible; x In addition to addressing known risks from nanomaterials, such those endpoints for which there are established mechanisms of action (e.g., DNA damage), NANOINTERACT also addressed the potential for new toxicological endpoints, such as nanoparticleinduced changes in protein aggregation and fibrillation,aswellaschangesinsubtlegeneandproteinregulationpathways; x The investigations focussed on several key classes of nanoparticles – silicon dioxide, cerium oxide, aluminium oxide (both particulate and monolithic surfaces),polystyrene,quantumdotsandgoldnanoparticlesbeingtheprinciple materialsusedacrossthestudies; x Localisation studies showed no evidence of direct contact between DNA and the nanoparticles, which were never detected in the nuclei and were always localisedinvesicularstructures,likelylysosomes; x The ecotoxicological research part of NANOINTERACT mainly involved aquatic studies with SiO 2 and CeO 2 . The unicellular green alga Pseudokirchneriella subcapitata was used as the primary test organism in algal growth inhibition assays. No toxicity was found for either SiO 2 or CeO 2 bulk powder at the maximumtestconcentrationsof1000mg/l; x Perhaps one of the most striking aspects of nanoparticlecell interactions, clearlydistinguishingnanomaterialsfromchemicals,istheissueofthe‘protein corona’. In essence, chemicals (generally) interact directly with biological elements,whereasnanoparticlesarecoatedbystronglyadheringproteinsand lipids, the exchange times of which are so long that the effective biological identity of the particles is greatly influenced (in some cases likely completely determined)bytheproteinsandnotthematerials.Veryconsiderableprogress has been made within the NANOINTERACT project towards elucidating the nature, identify, conformation and aggregation of proteins incorporated into nanoparticlecoronas, and towards understanding of the consequences of theseinteractionsforbothparticleandproteinstability; x NANOINTERACThasresultedinover40originalpeerreviewedpublications; x SomeofthedetailedprotocolsthatresultedfromNANOINTERACTarealready being shared with the wider scientific community via the NANOIMPACTNET protocolsdatabase; x Many of the concepts developed in the NANOINTERACT project have been taken up by the FP7funded project NEURONANO, and have fed into the NANOIMPACTNETcoordinationactionandotherprojects. 254 Coordinator: x University College Dublin, Centre for BioNano Interactions, Ireland (Prof.KennethDawson) Otherbeneficiaries: Organisation Country NationalUniversityofIreland,Galway IE LudwigMaximiliansUniversity,Munich DE UniversityofOxford UK TrinityCollege,Dublin IE UlsterUniversity,Coleraine UK UniversityofParisSud,Orsay FR LundUniversity SE NationalInstituteforPublicHealthandtheEnvironment(RIVM), NL Bilthoven NoferInstituteofOccupationalMedicine,ód PL BE GhentUniversity RiceUniversity,Houston,Texas US GlantreoGlan,Cork IE Medtronic,Galway IE L'Oréal,Paris FR Intel,Leixlip IE Umicore,Olen BE DSM,TeHeerlen NL WeizmannInstituteofScience,Rehovot IL 255 256 CONTRACTNUMBER:515843 PROJECTTYPE: Integratedproject TOTALPROJECTCOST: €12402348 ECCONTRIBUTION: €6999837 STARTINGDATE:April1,2005 ENDDATE:March31,2009 NANOSAFE2 SAFEPRODUCTIONANDUSEOFNANOMATERIALS Summary: 10 NANOSAFE2 was the followup of a first study supported by the European Commission from 2003 to2004entitledNANOSAFE(Riskassessmentinthe production and use of nanoparticles with the development of preventive measures and practice codes). NANOSAFE2 intended to develop innovative detection, traceability and characterisation techniques for engineered nanoparticles. It supplied nanotoxicologistswithamethodologybasedonaninnovativegenericapproachfor analysing the toxicity of nanoparticles. It also developed safe and costeffective measurestominimisetheexposureofworkers,consumersandtheenvironmentto manufactured nanoscale entities. It also supported a wide range of studies to evaluate current and future projected levels of exposure, the adequacy of current approaches to control exposure and propose measures and recommendations. One part of the project was devoted to the detection and the characterisation of engineered nanoparticles. Another part was concentratedonthetoxicityandthebodydistributionofnanomaterials.Athirdpart focused on the development of secure industrial production system and safe applications.Theprojectalsocarriedoutworkonlegislationandstandardisation,risk assessment and life cycle analysis, and pursued training dissemination activities. More details on results are available in the European NanoSafety Cluster Compendium2011. Potentialcontributiontothefollowingpolicies: x TheEuropeanstrategyfornanotechnologyandthenanotechnologyActionPlan x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Nanotechnologies and nanosciences, knowledgebased multifunctional materialsandnewproductionprocessesanddevices'thematicpriority 10 www.nanosafe.org 257 Mainresults: x x x x x x x x x x x x New traceability labels, specifically adapted to nanomaterials, were set up usingphosphornanotagsandoligonucleotides; Methodsandtoolsweredevelopedtomeasurethedensephasepropertiesof nanoparticles for explosion risk, the characterisation of nanoparticles in biologicalmedia,etc.; Numerous pieces of information on the actual levels and behaviour of the nanoparticles at workplaces were obtained. The results highlighted the necessity to develop new specific measurement tools less sensitive to backgroundfluctuations; It could clearly be shown that there are ways to produce and handle nanoparticles securely in an industrial environment using currently available toolsandmeans; New online aerosol measurement pieces of equipment were developed, such as a new condensation particle counter and two inexpensive pieces of equipment,specificallydesignedforcontinuousmonitoringofearlyevents:an electrostatic device without clogging effect and a device based on a smoke detector; Collection of nanoparticles on ultrapure filters before detection by elemental analysiswasinvestigated.Workfocusedonhowtopurifyultimatelythefilters intermsofmetalliccontamination; Two types of nanolabels carrying information such as manufacturer name, batchproductionnumber,toxicity,physicalproperties,etc.,weredeveloped; Theconsortiumshowedthatthecytotoxicityofnanomaterialswasinfluenced by several confounding factors and therefore several controls have to be includedtoproduceconclusivedata; Translocationstudiescarriedoutinratswereusedtofeedthedevelopmentof generic numerical physiological toxicokinetic/toxicodynamic (PBPK) model, predictiveofnanoparticleinternalexposureandpotentialhealtheffects; AthoroughreviewofmainEUlegislationandstandardswasperformedandled toapositionpaperpresentedattheNanosafe2008conference,andpublished inthe'JournalofPhysicsConferenceSeries'. The project contributed to the development of the following ISO and CEN documents:(i)ISO/TR27628'WorkplaceatmospheresUltrafine,nanoparticle and nanostructured aerosols Inhalation exposure characterisation and assessment'; (ii) PG5/WG3 'Guidance on physicochemical characterisation of engineered nanoscale materials for toxicological assessment' (ISO TC229); (iii) PG10/WG2 'General Framework for determining nanoparticle content in nanomaterials by generation of aerosols (e.g. dustiness)' (ISO TC 229); (iv) TR ISOTR27628'Ultrafine,nanoparticleandnanostructuredaerosolsInhalation exposure characterization and assessment'; and (v) 'Guide of nanoparticle measurementmethodsandtheirlimitations'(CEN/TC352); NANOSMILE portal was constructed to help bridge the societal gap between research&industryandthepublic.Thisportal,freeofcharge,providesabout8 hoursofmaterialconsultation. 258 Coordinator: x FrenchNuclearEnergyCommission(CEA),Grenoble(Dr.FrédéricSchuster) Otherbeneficiaries: Organisation Procter&GambleEurocorNV,StrombeekBever BASFSE,Ludwigshafen ARKEMA,Paris IntrinsiqMaterialsLtd,Bristol NanogateAdvancedMaterialsGMBH,Saarbrücken OxonicaLtd,Kidlington CatholicUniversityofLeuven CSEMSA,Neuchatel CenterofAdvancedEuropeanStudiesandResearch(CAESAR), Bonn UniversityofOxford UniversityofGlasgow NationalInstituteofHealthandMedicalResearch(INSERM), Paris VTTTechnicalResearchCentre,Espoo HelmholtzResearchCentreforEnvironmentalHealth,Munich JožefStefanInstitute,Ljubljana UniversityCollegeLondon NationalInstituteforIndustrialEnvironmentandRisks(INERIS), VerneuilenHalatte HealthandSafetyExecutiveHealthandSafetyLaboratory, Buxton SwissiInstituteforthePromotionofSafetyandSecurity,Zürich GermanSocialAccidentInsurance(DGUV),SanktAugustin DekatiOy,Tampere Umicore,Olen 259 Country BE DE FR UK DE UK BE CH DE UK UK FR FI DE SI UK FR UK CH DE FI BE 260 CONTRACTNUMBER:32777 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST:€3995225 ECCONTRIBUTION:€2399234 STARTINGDATE:November1,2006 ENDDATE:October31,2009 DURATION:36months NANOSH INFLAMMATORYANDGENOTOXIC EFFECTSOFENGINEERED NANOMATERIALS Summary: 11 The overall goal of the project was to characterise the levels of exposure to specific engineered nanoparticles and to delineate the health effects of selected nanosizedparticlesrelevanttotheoccupationalenvironment.Exposurelevelswere evaluated both under laboratory conditions and during the manufacture of the particles. The particles were characterised with respect to their morphology and particle size distribution, surface activity, and potential for agglomerate formation. The health effects studied included genotoxicity, pulmonary inflammatory responses, and effects on the vasculature. The information gathered, together with the stateoftheart technology utilised in these studies, increased our knowledge on nanoparticles and helped to create a reliable basis for the evaluation of possible health risks associated with these new materials. The consortium developed models for a thorough characterisation of nanoparticlesandtheirdispersions,whichwereusedinthetoxicitytestsperformed during the project. Exposure measurements were carried out in many types of workplaces.Methodsweredevelopedforgenotoxicityassessmentofnanomaterials in vitro and in vivo. In addition to size and shape, the surface chemistry of nanomaterialsstronglyaffectstheirfateaswellastheirbiologicaleffectsinvitroand in vivo. The project provided essential information, which can be used on a wider basisforassessingoccupationalandothersafetyrisksassociatedwiththeproduction and use of nanoparticles. More details on results are available in the European NanoSafetyClusterCompendium2010. Potentialcontributiontothefollowingpolicies: x TheEuropeanstrategyfornanotechnologyandthenanotechnologyActionPlan x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Nanotechnologies and nanosciences, knowledgebased multifunctional materialsandnewproductionprocessesanddevices'thematicpriority 11 www.ttl.fi/partner/nanosh 261 Mainresults: x Particle characterisation: The consortium developed models for a thorough characterisationofnanoparticlesandtheirdispersions,whichwereusedinthe toxicity tests performed during the project. The models have been published and can be utilised by people outside the consortium. A number of nanomaterials were selected for the NANOATLAS database (available both in printed and electronic form), providing examples of the most relevant nanomaterials used in commercial applications, such as carbon nanotubes, fullerenes, metal particles, metal oxide particles, quantum dots and some experimentalnanoparticles; x Exposure assessment: A strategy for assessing exposure to engineered nanoparticles (ENPs) in a range of workplaces was developed. Solutions for background discrimination were explored. A decision logic for determining whether workers were likely to be exposed to ENPs was developed. Measurements were carried out in many types of workplaces from university research laboratories to largescale production plants, where a wide range of ENPsareproducedorhandled; x Genotoxicity of nanoparticles: Methods were developed for genotoxicity assessmentofnanomaterialsinvitroandinvivo.Mostnanoparticleswereable to damage DNA in vitro, and for TiO 2 this seemed to be due to primary oxidative DNA damage. Some nanomaterials were also capable of increasing chromosomedamageinvitro,zincoxideshowingtheclearesteffect.Inhalation ofTiO 2 didnotaffectthelevelofDNAorchromosomedamageinmice; x Pulmonary inflammation: In vivo tests showed that healthy mice elicited pulmonary neutrophilia accompanied by chemokine CXCL5 expression, when exposedtonanosizedTiO 2 .Asthmaticmiceshowedremarkablesuppressionof mostmediatorsandsignsofallergicasthma,whenexposedtoeithernanosized orcoarseTiO 2 ; x Microvasculareffectsparticles:Thefindingsstronglycorroboratetheviewthat, inadditiontosizeandshape,thesurfacechemistryofnanomaterialsstrongly affectstheirfateaswellastheirbiologicaleffectsinvitroandinvivo; x Theprojectprovidesessentialinformation,whichcanbeusedonawiderbasis forassessingoccupationalandothersafetyrisksassociatedwiththeproduction and use of nanoparticles. Essential products that serve these scientific and technologicalgoalsaremeansandmethodstocharacteriseparticleproperties, waystocarryoutreliableexposureassessments,andmodelsforassessingkey health effects all important components of the safety evaluation of engineerednanoparticles; x Theresultsobtainedhavebeenpublishedasoriginalscientificarticles. 262 Coordinator: x FinnishInstituteofOccupationalHealth,Helsinki(Prof.KaiSavolainen) Otherbeneficiaries: Organisation Country UniversityofMunich,InstituteforSurgicalResearch DE CentralInstituteforLabourProtection–NationalResearch PL Institute,Warsaw InstituteofAppliedScientificResearch(TNO),Zeist NL HealthandSafetyExecutiveHealthandSafetyLaboratory, UK Buxton GermanSocialAccidentInsurance(DGUV),SanktAugustin DE UniversityofLeicester UK 263 264 CONTRACTNUMBER:18486 PROJECTTYPE:Coordinationaction TOTALPROJECTCOST:€1899831 ECCONTRIBUTION:€1899831 STARTINGDATE:September1,2005 ENDDATE:November30,2008 DURATION:39months NORMAN NETWORKOFREFERENCELABORATORIES ANDRELATEDORGANISATIONSFOR MONITORINGANDBIOMONITORINGOF EMERGINGENVIRONMENTALPOLLUTANTS Summary: There are great numbers of emerging substancesthatarepotentiallyresponsiblefor adverse environmental effects. They include pharmaceuticals, phytosanitary products, surfactants, personal care products, etc. The need to look beyond the traditional target pollutants, when assessing the hazards of chemicals to human health and to ecosystems, is now generally recognisedasapriorityissueinallpolicyareasat both the European and national level. The 12 NORMAN network started its activities in September 2005 and it is now established as a permanent selfsustaining network of reference laboratories, research centres and related organisations for the monitoring and biomonitoring of emerging environmentalsubstances.Itsmissionisto(i)enhancetheexchangeofinformation and collection of data on emerging environmental substances; (ii) encourage the validation and harmonisation of common measurement methods and monitoring toolssothatthedemandsofriskassessors canbebettermet;and(iii)ensurethat knowledge on emerging pollutants is maintained and developed by stimulating coordinated, interdisciplinary projects on collaborative, problemoriented research andknowledgetransfertoaddressidentifiedneeds. Potentialcontributiontothefollowingpolicies: x Regulation (EC) no 1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x Council directive 98/83/EC on the quality of water intended for human consumption x CouncilDirective91/271/EECconcerningurbanwastewatertreatment x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Sustainabledevelopment,globalchangeandecosystems'thematicpriority 12 www.normannetwork.com/index_php.php 265 Mainresults: x Identification of the key European organisations and experts in the field of emerging pollutants in order to prepare the ground for the extension of the corenetwork; x Creation of a permanent website describing continuous activities undertaken bythenetwork(newsletters,meetings,positionpapersetc.); x Appointment of NORMAN Contact Points facilitate the regular exchange and gathering of information on emerging substances from national reports and research initiatives, including information that appears in the socalled grey literature; x Development of three databases: EMPOMAP (database of leading experts, organisations and projects dealing with emerging substances), EMPODAT (a database of georeferenced monitoring data accompanied by ecotoxicological information from bioassays and biomarkers; contains over 8000 entries) and EMPOMASS (database of mass spectrometric information on provisionally identifiedandunknownsubstances); x Creation of the NORMAN in February 2009 as a nonprofit association under FrenchLaw1901.Theorganisationsthathadexpressedaninterestinbecoming ordinary members were invited to apply formally to become members of the association with formal acceptance of the statutes. In 2010, the NORMAN Association has eight founding members and more than 40 organisations as ordinary members, many of them among the most highly regarded in Europe andonememberfromCanada. 266 Coordinator: x National Institute for Industrial Environment and Risks (INERIS), Verneuilen Halatte,France(Dr.ValeriaDulio) Otherbeneficiaries: Organisation Country OfficeofGeologicalandMiningResearch,Orléans FR FrenchResearchInstituteforAgriculturalandEnvironmental FR Engineering(CEMAGREF),Antony VUUniversity,Amsterdam NL FederalEnvironmentAgency,Berlin/DessauRosslau DE WaterResearchCentre(IWW),MülheimanderRuhr DE SpanishNationalResearchCouncil(CSIC),Madrid ES JožefStefanInstitute,Ljubljana SI NO BiosenseLaboratoriesAS,Bergen StockholmUniversity,DepartmentofAppliedEnvironmental SE Science,Stockholm EnvironmentAgency,Rothley UK WaterResearchInstitute,Bratislava SK EnvironmentalInstitute,Koš SK NationalPhysicalLaboratory,Teddington UK CommissionoftheEuropeanCommunitiesDirectorate IT GeneralJointResearchCentre,Ispra FraunhoferInstitute,München DE NL NationalInstituteforPublicHealthandtheEnvironment (RIVM),Bilthoven 267 268 CONTRACTNUMBER:12912 PROJECTTYPE: Specifictargetedresearchproject TOTALPROJECTCOST: €1115878 ECCONTRIBUTION:€799576 STARTINGDATE:June1,2005 ENDDATE:August31,2008 DURATION:39months PARTICLE_RISK RISKASSESSMENTOFEXPOSURETO PARTICLES Nowebsite Summary: Some new and emerging sciences and technologies (NEST) have the potential to generate particulates, which can enter the bodyviainhalation,ingestionordermalabsorption.Asnewmaterialsaregenerated from sources as diverse as novel combustion systems, nanotechnology or pharmaceutical drug delivery in the life sciences, there is potential for human exposure. Inhalation exposure to dusts leads to pulmonary diseases and particle toxicityincreaseswithdecreasingparticlesize.Informationisneededregardingthe possible risks from exposure to these particles including: the routes of exposure and subsequent disposition; their potential toxicity; appropriate toxicological testing procedures; and susceptible subpopulations. This project has acquired a bank of particles potentially generated by NEST (NESTP) and assessed the health risk from exposure to thesematerialsthroughairorthefoodsupplywith aworkprogramme,integratinginvitroexperiments, animalmodelsofhealthy/susceptibleindividualsandexposure/riskassessment. Potentialcontributiontothefollowingpolicies: x TheEuropeanstrategyfornanotechnologyandthenanotechnologyActionPlan x Regulation (EC)1907/2006 concerning the Registration, Evaluation, AuthorisationandRestrictionofChemicals(REACH) x EuropeanEnvironmentandHealthStrategy[COM(2003)338] EUfunding: x 'Newandemergingscienceandtechnologies(NEST)'programme 269 Mainresults: x x x x x x x Techniquesweredevelopedforcharacterisingthephysicochemicalproperties oftheselectedNESTP.Itwasfoundthatnoindividualtechniquecansatisfya meaningfulcharacterisationofNESTP.Theoptimumsetofrequiredtechniques shouldbeselectedonthebasisoftheinvestigatedNESTPtype; It was found that positively charged quantum dots (QD621) have effects on glutathione (GSH) depletion, cytotoxicity and inhibition of bile production in vitro; Asregardsinvivopulmonaryeffectsinmice,itwasfoundthattheexpression of inflammatory marker mRNA was increased in lung tissue for positively and negativelychargedQDsand,toalesserextent,singlewalledcarbonnanotubes andcarbonblack; Allnanoparticles(NPs)showedincreasedgenotoxicitymeasuredbythecomet assayonbronchoalveolarlavage(BAL)cells3hoursafterinstillation; Fourlinesofevidence(LOEs)wereintegratedintoaweightofevidence(WoE) approach to assess the hazard of NPs. The use of physicochemical characterisation and biological responses under laboratory conditions may be considered a preliminary tool to carry out hazard ranking of tested NPs. This methodology, based on the evaluation of a set of NPs properties and effect endpointsunderanintegratedframework,allowstheprovisionofafirstlineof hazard evidence, where data and information on exposure and effect of manufacturedNPsareveryscarce; Various measured physicochemical properties and effect data were obtained. However, the measurement data differed in uncertainty and in reliability for suggesting harm to humans. It was assumed that all LOE and indicators were equallyimportantintheoverallcalculationofhazard,butfurtherdevelopment of the WoE method could be included an “ad hoc” procedure for weighting them and then for highlighting their relative importance, e.g., by expert judgment. This case study showed then the utility of the WoE procedure and suggested thatvariousLoEscanbedefinedtoprovideconclusionabouthazardofNPs. Coordinator: x InstituteofOccupationalMedicine,Edinburgh(Dr.LangTran) Otherbeneficiaries: Organisation UniversityofEdinburgh NapierUniversity,Edinburgh VeniceResearchConsortium(CVR) UniversityofVenice InstituteofLungBiologyandDisease,Neuherberg NationalInstituteofOccupationalHealth,Copenhagen 270 Country UK UK IT IT DE DK CONTRACTNUMBER:12719 PROJECTTYPE:Specifictargeted researchproject TOTALPROJECTCOST:€1132900 ECCONTRIBUTION:€795000 STARTINGDATE:October1,2005 ENDDATE:March31,2008 DURATION:30months POLYSOA POLYMERSINSECONDARYORGANIC AEROSOLS Summary: Recent experiments have shown that organic material in secondary organic aerosols(SOA)canpolymerise,leadingto newhighmolecularweightcompoundswithmassupto1000Da.Suchpolymersare of concern regarding their potential adverse health effects and impact on air quality and climate. High molecular weight compounds have been found in ambientaerosols,buttheiroriginisunknownandtheir 13 identification rudimentary. The POLYSOA project appliedanddevelopeddifferentsophisticatedanalytical methodstomeasurehighmolecularweightcompounds of this SOA polymer fraction and characterised its chemicalandphysicalbulkparameters.Injointmeasurementcampaignsinasmog chamber, a combined effort was undertaken to identify and characterise these polymersproducedfromdifferentprecursors,whichdominateinanthropogenicand biogenicemissionsources.Simultaneously,theseSOApolymerswereappliedonline to cell culture systems, which are representative of the inner surface of airways and/orpulmonaryalveoli. Potentialcontributiontothefollowingpolicies: x Climatechangepolicies EUfunding: x 'Newandemergingscienceandtechnologies(NEST)'programme 13 http://polysoa.web.psi.ch 271 Mainresults: x The exposure experiments occurred under realistic conditions and the results ofthePOLYSOAcampaignsindicatethatSOA(inconcentrationscomparableto environmental concentrations) may induce distinct effects on lung cells. The dataobtainedhavedemonstratedthatatwohourexposureofthevariouslung 3 celltypestoSOAatambientairconcentrationsofabout104particles/cm leads toonlymoderatecellularresponses; x However,thereisevidenceforcellspecificeffectsandfordifferent effectsof SOA originating from anthropogenic and from biogenic precursor molecules, i.e.,1,3,5trimethylbenzene(TMB)and pinene; x SOA affected the phagocytic activity of macrophages, the release of lactate dehydrogenase(LDH)aswellasthereleaseof(pro)inflammatorycytokines.In addition,thereisfirstevidencefromthePOLYSOAcampaignsfordifferencesof thecellularresponsesdependingontheprecursormoleculesofSOA; x Controlexperimentswithinertpolystyreneparticles,however,didnotresultin changesinanyofthebiologicalendpointsthatwereassessed. Coordinator: x PaulScherrerInstitute,Villingen,Luxembourg(Dr.UrsBaltensperger) Otherbeneficiaries: Organisation Country InstituteofAtmosphericSciencesandClimate,Rome IT UniversityofBern CH UniversityofMainz DE JohannesGutenbergUniversity,Mainz DE TechnicalUniversityofVienna AT 272 CHAPTERVI – OtherProjectsofInterest CHAPTERVI Otherprojectsofinterest 273 274 H EALTH Otherprojectsofinterest,notdetailedinthecatalogue BRAFOSpecificsupportactionto investigatetheriskbenefitanalysis forfoods (Specificsupportaction) CAIR4HEALTHCleanairforhealth– researchneedsforsustainable developmentpolicies (Specificsupportaction) CAIR COST281Potentialhealth implicationsfrommobile communicationsystems (COSTaction) CRESCENDOConsortiumfor researchintonuclearreceptorsin developmentandaging (Integratedproject) EUROLYMPHCollaborative Europeanactionintoenvironmental, nutritionalandgeneticfactorsinNon hodgkin’slymphomaaetiology (Specificsupportaction) NANOTOXInvestigativesupportfor theelucidationofthetoxicological impactofnanoparticlesonhuman healthandtheenvironment (Specificsupportaction) RAINBOWResearchonanimaland invitrostudiesandnumerical methods:bridgingopportunities throughaworkshop (Specificsupportaction) RETHINKMinipigsasmodelsforthe toxicitytestingofnewmedicinesand chemicals:impactassessment (Specificsupportaction) TESTMETEDECODevelopmentof testmethodsforthedetectionand characterisationofendocrine disruptingchemicalsinenvironmental species (Specificsupportaction) 275 www.brafo.org www.cair4health.eu www.cost.esf.org/domains _actions/ict/Actions/281 www.crescendoip.org www.rainbowproject.eu http://minipigs.dk/fileadmi n/filer/Publications/Rethin k__Article_1.pdf 276 AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects AnnexA Participatingcountriesandinstitutesin FP6fundedenvironmentandhealthprojects 277 278 AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects EUROPEANUNIONMEMBERSTATES AUSTRIA(AT) ARCSeibersdorfResearchGmbh,Seibersdorf AustrianFederalEnvironmentAgency,Vienna BiomayAG,Vienna FactlineWebservicesGmbH,Vienna InnsbruckMedicalUniversity InterdisciplinaryCentreforComparativeResearchin theSocialSciences,Vienna InternationalAssociationforCerealScienceand Technology,Vienna InternationalAssociationforDanubeResearch,Vienna InternationalInstituteforAppliedSystemsAnalysis, Laxenburg MedicalUniversityofVienna TechnicalUniversityofGraz TechnicalUniversityofVienna UniversityofNaturalResourcesandAppliedLife Sciences,Vienna UniversityofSalzburg UniversityofViennaMedicalSchool VBCGenomicsBioscienceResearchGmbh,Vienna WebbStephenMatthew,Vienna BELGIUM(BE) AviaGis,Zoersel CatholicUniversityofLeuven CatholicUniversityofLouvain,Brussels, LouvainlaNeuve Centred'EconomieRurale–Hormonology Department,Marloie DNAVision,Charleroi EggCentrisNV,Zellik ExxonmobilPetroleum&ChemicalBVBA,Antwerp 279 EMFNET ESBIO EUROPREVALL FOOD&FECUNDITY CARCINOGENOMICS, PREDICTOMICS MONIQA MONIQA HEALTHYWATER ENSEMBLES EUROPREVALL,PRONET EMFNET POLYSOA CIRCE,GABRIEL,MONIQA, REPROTECT DIPNA,NOMIRACLE 2 GA LEN EUROPREVALL MONIQA EDEN ECNIS,ESBIO,IMPART, NANOSAFE2,NEWGENERIS ACUTETOX,DEVNERTOX, EDEN,ENSEMBLES, INTARESE,MICRODIS,PHIME MONIQA EXERA REPROTECT NHRDEVTOX AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects FlemishInstituteforTechnologicalResearch(VITO), Mol FreeUniversityofBrussels GhentUniversity InstituteofPublicHealth,Brussels Johnson&JohnsonPharmaceutical Research&Development,Beerse NanocylSA,Auvelais Procter&GambleEurocorNV,StrombeekBever Umicore,Olen UniversityofAntwerp BULGARIA(BU) AppelEuropa,Sofia Bourgas'ProfessorAssenZlatarov'University,Bourgas BulgarianAcademyofSciences,Sofia MedicalUniversity,Sofia UniversityofFoodTechnologies,Plovdiv CYPRUS(CY) StateGeneralLaboratory,Nicosia CZECHREPUBLIC(CZ) CharlesUniversity,Prague CzechHydrometeorologicalInstitute,Prague FacultyHospitalBulovka,Prague InstituteofAtmosphericPhysics,Prague 280 ATHON,DIPNA,EMFNET, ESBIO,2FUN,HEIMTSA, INTARESE,REPROTECT, SENSITIV ACUTETOX, CARCINOGENOMICS,ECNIS, NEWGENERIS,PREDICTOMICS, REPROTECT 2 GA LEN,NANOINTERACT ACUTETOX PREDICTOMICS,REPROTECT NANOTOX BRAFO,NANOSAFE2 NANOINTERACT,NANOSAFE2 EDEN,HENVINET, NOMIRACLE,OSIRIS EUROPREVALL NOMIRACLE,OSIRIS, REPROTECT IMPART,NANOTOX EUROPREVALL MONIQA ESBIO,VIROBATHE DROPS,ENSEMBLES,ENVIE, HEIMTSA,METHODEX, NHRDEVTOX,PHOEBE, VERHICHILDREN ENSEMBLES,ESPREME, HEIMTSA EUROPREVALL ENSEMBLES AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects InstituteofExperimentalMedicine,Prague InstituteofMolecularGeneticsASCR,Prague InstituteofVertebrateBiology,Brno NationalInstituteofPublicHealth,Prague OstravaInstituteofPublicHealth PalackýUniversity,Olomouc RegionalInstituteofPublicHealth,Kolin UniversityofDefence,HradecKrálové VeterinaryResearchInstitute,Brno DENMARK(DK) AarhusSchoolofBusiness AarhusUniversity,Aarhus,Roskilde AarhusUniversityHospital DanishEpidemiologyScienceCentre,Copenhagen DanishMeteorologicalInstitute,Copenhagen DanishNationalEnvironmentalResearchInstitute, Roskilde DanishVeterinaryandFoodAdministration,Søborg DHIWaterandEnvironment,Horsholm EllegaardGottingenMinipigsAPS,Dalmose FaroeseHospitalSystem,Tórshavn NationalInstituteofOccupationalHealth, Copenhagen Novozymes,Bagsvaerd OdenseUniversityHospital ReflabAPS,Copenhagen ResearchCentreFlakkebjerg,Slagelse RoyalVeterinaryandAgriculturalUniversity(KVL), Frederiksberg TechnicalUniversityofDenmark,KongensLyngby UniversityofCopenhagen UniversityofSouthernDenmark,Odense 281 DIEPHY,ENVIRISK,INTARESE CRESCENDO EDEN ESBIO,INTARESE, NOMIRACLE,PHIME, SAFEFOODS 2FUN ACUTETOX ENVIRISK NHRDEVTOX ATHON EUROPREVALL ENSEMBLES,ENVIE, EUROPREVALL,GABRIEL, NOMIRACLE,OSIRIS FOOD&FECUNDITY NEWGENERIS CIRCE,ENSEMBLES PRONET BENERIS RETHINK PHIME PARTICLE_RISK CARCINOGENOMICS, SENSITIV 2 GA LEN EUROPREVALL PHIME PHIME,SAFEFOODS BENERIS,ENVIE, EUROPREVALL,2FUN, HEIMTSA,OSIRIS, SAFEFOODS ECNIS,ESBIO,NEWGENERIS, REPROTECT HENVINET,PHIME AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects ESTONIA(EE) EstonianGenomeProjectFoundation,Tartu NationalInstituteforHealthDevelopment,Tallinn NationalInstituteofChemicalPhysicsandBiophysics, Tallinn FINLAND(FI) DekatiOy,Tampere FinnishEnvironmentInstitute,Helsinki FinnishForestResearchInstitute,Vantaa FinnishInstituteofOccupationalHealth,Helsinki FinnishNationalInstituteforHealthandWelfare (THL),Helsinki,Kuopio(exKTL) FinnishMeteorologicalInstitute,Helsinki HelsinkiUniversityCentralHospital HelsinkiUniversityofTechnology HormosMedicalPharmacity,Turku KuopioUniversityHospital RadiationandNuclearSafetyOrganization(STUK), Helsinki OuluUniversity OyFoodfilesLtd,Kuopio OyJurilabLtd.,Kuopio UniversityofEasternFinland(exUniversityofKuopio) UniversityofHelsinki UniversityofTurku VTTTechnicalResearchCentre,Espoo 282 PHOEBE EDEN,ESBIO OSIRIS NANOSAFE2 ENSEMBLES,NOMIRACLE EDEN ECNIS,EMFNET,ESBIO, MICRODIS,NANOSH ATHON,BENERIS,ENVIE, ENVIRISK,GABRIEL,HEIMTSA, HIWATE,INTARESE,PHOEBE CAIR4HEALTH,ENSEMBLES, HENVINET 2 GABRIEL,GA LEN ENVIE,IMPART,NANOTOX EXERA PIONEER EMFNET ACUTETOX BENERIS PHIME EMFNET,NEWGENERIS, REPROTECT,SAFEFOODS CASCADE,CRESCENDO,EDEN, PIONEER CASCADE,EXERA,PIONEER MONIQA,NANOSAFE2 AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects FRANCE(FR) ARKEMA,Paris Armines,Paris ArtoisUniversity,Lens BiochemicsConsultingSAS,Olivet BiopredicInternational,Rennes CentreforBioActiveMoleculesScreening(CMBA), Grenoble CERFACS,Toulouse Climpact,Paris EcoleCentraledeLyon,Lyon EcoleNormaleSupérieure(ENS),Lyon,Paris ElectricitédeFrance(EDF),Chatou ÉcoledesPontsParisTech,ChampssurMarne FederationofFrenchElectrical,Electronic& CommunicationIndustries(FIEEC),Paris FERURBATSARL,Clamart FranceTelecom,IssylesMoulineaux FrenchAgencyforEnvironmentalandOccupational HealthSafety(AFSSET),MaisonsAlfort FrenchBuildingResearchandTechnologyInstitute (CSTB),ChampssurMarne FrenchNationalCentreforGenotyping,Evry FrenchNationalCentreforScientificResearch(CNRS), Nouzilly FrenchNationalCentreforScientificResearch(CNRS), Paris FrenchNationalCentreforScientificResearch(CNRS), Villejuif FrenchNationalInstituteforAgriculturalResearch (INRA),MontferriersurLez FrenchNationalInstituteforAgriculturalResearch (INRA),Nouzilly FrenchNationalInstituteforAgriculturalResearch (INRA),Paris FrenchNationalInstituteforAgriculturalResearch (INRA),Toulouse FrenchNationalInstituteforHealthSurveillance (INVS),StMaurice FrenchNationalInstituteforIndustrialEnvironment andRisks(INERIS),VerneuilenHalatte FrenchNationalInstituteofHealthandMedical Research(INSERM),Evry 283 NANOSAFE2 METHODEX ACUTETOX CAESAR CARCINOGENOMICS ACUTETOX ENSEMBLES ENSEMBLES OSIRIS CASCADE,ENSEMBLES ENSEMBLES,2FUN HEIMTSA EMFNET MICRODIS EMFNET INTARESE INTARESE GABRIEL FOOD&FECUNDITY CASCADE,CRESCENDO, PIONEER EMFNET EDEN FOOD&FECUNDITY EUROPREVALL,SAFEFOODS CASCADE ESBIO,INTARESE 2FUN,INTARESE, NANOSAFE2,NORMAN GABRIEL AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects FrenchNationalInstituteofHealthandMedical Research(INSERM),Grenoble FrenchNationalInstituteofHealthandMedical Research(INSERM),Lyon FrenchNationalInstituteofHealthandMedical Research(INSERM),Paris FrenchNationalInstituteofHealthandMedical Research(INSERM),Toulouse FrenchNationalInstituteofHealthandMedical Research(INSERM),Villejuif FrenchNationalInstituteofHealthandMedical Research(INSERM),Montpellier FrenchNuclearEnergyCommission(CEA),Grenoble, Paris FrenchResearchInstituteforAgriculturaland EnvironmentalEngineering(CEMAGREF),Antony GraduateSchoolofChemistry,BiologyandPhysics ofBordeaux(ENSCBP) HenriPoincaréUniversity,Nancy Imstar,Paris InternationalCentreforToxicology,Evreux InternationalEnvironmentandDevelopment ResearchCentre(CIRED),NogentsurMarne InstituteforResearchandDevelopment(IRD), Montpellier InstituteofGeneticsandMolecularandCellular Biology,Illkirch InstituteofSustainableDevelopmentand InternationalRelations,Paris InstitutPasteur,Paris InterdepartmentalArrangementforMosquito ControlofMediterraneanCoast(EID),Montpellier InternationalCentreofCooperationinAgronomic ResearchforDevelopment(CIRAD),Montpellier L'Oréal,Paris LouisPasteurUniversity,Strasbourg MediasFrance,Toulouse MétéoFrance,Paris OfficeofGeologicalandMiningResearch(BRGM), Orléans PfizerGlobalResearch,Amboise Servier,Suresnes PierreSimonLaplaceInstitute,Guyancourt,Paris SMASH,Paris StrasbourgUniversityHospital SUEZEnvironement,LePecq SymlogdeFranceInstitute,Cachan 284 CELLNANOTOX CELLNANOTOX CRESCENDO,FOOD& FECUNDITY,NANOSAFE2 PHOEBE 2 GA LEN CASCADE,PREDICTOMICS NANOSAFE2 NORMAN EMFNET VIROBATHE NEWGENERIS RETHINK CIRCE EDEN CRESCENDO CIRCE EDEN EDEN CIRCE,EDEN NANOINTERACT,SENSITIV SENSITIV CIRCE CIRCE,ENSEMBLES NORMAN REPROTECT CRESCENDO CIRCE,ENSEMBLES ENSEMBLES EUROPREVALL HEALTHYWATER NOMIRACLE AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects UniversityofFrancheComté,Besançon University'JosephFourier'Grenoble1 UniversityofMontpellier1 UniversityofNiceSophiaAntipolis,Nice UniversityofParisSud,Orsay UniversityofRennes1 GERMANY(DE) AlbertLudwigsUniversity,Freiburg AnalytischesLaboratoriumLuhnstedt AssociationforTechnologyandStructuresin Agriculture(KTBL),Darmstadt BASFSE,Ludwigshafen BayerHealthCareAG,Wuppertal BavarianHealthandFoodSafetyAgency, Oberschleissheim BiochemicalInstituteforEnvironmentalCarcinogens, Prof.Dr.GernotGrimmerFoundation,Grosshansdorf BIPROGMBH,Munich CenterofAdvancedEuropeanStudiesandResearch (CAESAR),Bonn CharitéUniversityMedicalCenter,Berlin DialogikGmBH,Stuttgart EberhardKarlsUniversity,Tübingen ECTOekotoxikologieGmbH,FlörsheimamMain EMCMicrocollectionsGmbH,Tübingen EurofinsAnalytikGMBH,Hamburg EurohandelsinstitutGMBH,Köln EuropeanClimateForum,Potsdam EvaplanGMBH,Heidelberg FederalEnvironmentAgency,Berlin/DessauRosslau FoodInformationServiceEurope,BadBentheim FraunhoferInstitute,Hannover FraunhoferInstitute,München FraunhoferInstitute,St.Ingbert FreeUniversityofBerlin GermanCancerResearchCenter,Heidelberg GermanFederalInstituteforRiskAssessment(BFR), Berlin GermanSocialAccidentInsurance(DGUV),Sankt Augustin 285 GABRIEL ENSEMBLES EDEN HEALTHYWATER NANOINTERACT HIWATE SENSITIV OSIRIS HEIMTSA CELLNANOTOX,NANOSAFE2 ACUTETOX,PREDICTOMICS, REPROTECT VIROBATHE DIEPHY,ECNIS ESBIO NANOSAFE2 EUROPREVALL,GABRIEL, GA2LEN,PIONEER NOMIRACLE,OSIRIS, SAFEFOODS CASCADE,NOMIRACLE NOMIRACLE,OSIRIS GABRIEL MONIQA EUROPREVALL CIRCE MICRODIS ESBIO,NORMAN,VIROBATHE EUROPREVALL ACUTETOX,EMFNET, SENSITIV NORMAN,OSIRIS DIPNA CIRCE,ENSEMBLES CRESCENDO,ECNIS, EUROLYMPH,NEWGENERIS REPROTECT,SAFEFOODS NANOSAFE2,NANOSH AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects GermanStatutoryAccidentInsurance,Bochum GermanWeatherService,Hamburg GeorgAugustUniversity,Göttingen GrimmAerosolTechnikGmbh&CoKG,Ainring HelmholtzCentreforEnvironmentalResearch,Leipzig HelmholtzCentreforInfectionResearch, Braunschweig HelmholtzResearchCentreforEnvironmentalHealth, Munich IALAutomationundLogistikGMBH,Rötgen InstituteforCoastalResearch,Geesthacht InstituteofLungBiologyandDisease,Neuherberg JohannesGutenbergUniversity,Mainz KnowledgeMinerSoftware,Panketal KraftFoodsR&D,Munich LeibnizInstituteofMarineSciences,Kiel LeibnizInstituteofPlantBiochemistry,Halle LEMNATECGMBH,Würselen LimCoInternational,Ibbenbüren LudwigMaximiliansUniversity,Munich MaxPlanckInstituteforBiogeochemistry,Jena MaxPlanckInstituteforChemistry,Mainz MaxPlanckInstituteforImmunobiologyand Epigenetics,Freiburg MaxPlanckInstituteforMeteorology,Hamburg MaxPlanckInstituteforMolecularGenetics Munich MaxPlanckInstituteofMolecularPlantPhysiology, Potsdam MaxPlanckInstituteofPsychiatry,Munich MaxRubnerInstitute,Karlsruhe MerckKGaA,Darmstadt MiltenyiBiotecGmbH,BergischGladbach MinistryoftheEnvironmentandConservation, AgricultureandConsumerProtectionoftheStateof NorthRhineWestphalia,Düsseldorf MunichUniversityChildren'sHospital NanogateAdvancedMaterialsGMBH,Saarbrücken PaulEhrlichInstitute,Langen PotsdamInstituteforClimateImpactResearch ProteomeSciencesR&DGmbH&Co.KG,Frankfurt ProteoSysAG,Mainz 286 ATHON ENSEMBLES CASCADE DIPNA CAESAR,2FUN,NOMIRACLE, OSIRIS HEALTHYWATER CASCADE,CRESCENDO, EUROPREVALL,GABRIEL, INTARESE,NANOSAFE2 EUROPREVALL CIRCE,ENSEMBLES PARTICLE_RISK CASCADE,CELLNANOTOX, ECNIS,POLYSOA CAESAR EUROPREVALL ENSEMBLES PHIME NOMIRACLE NOMIRACLE 2 EDEN,GA LEN, NANOINTERACT CIRCE CIRCE SENSITIV CIRCE,ENSEMBLES CARCINOGENOMICS PHIME CRESCENDO BRAFO OSIRIS SENSITIV PRONET GABRIEL NANOSAFE2 EUROPREVALL CIRCE,ENSEMBLES SENSITIV REPROTECT AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects PublicHealthServiceofBadenWürttemberg, Stuttgart ResearchCenterBorstel ResearchAssociationforRadioApplications,Bonn RuhrUniversity,Bochum RuprechtKarlsUniversity,Heidelberg RWTHAachenUniversity TechnicalUniversityMunich Tp21GmbH,Saarbrücken UniversityofAppliedSciences,Stuttgart UniversityHospitalHeidelberg UniversityofBonn UniversityofFreiburg UniversityofHamburg UniversityofKassel UniversityofKonstanz UniversityofLeipzig UniversityofMunich UniversityofMünster UniversityofStuttgart UniversityofUlm UniversityofVeterinaryMedicine,Hannover UniversityofWürzburg TechnicalUniversityofKaiserslautern VDITechnologiezentrumGmbH,Düsseldorf VerumFoundationforBehaviourandEnvironment, Munich WaterResearchCentre(IWW),MülheimanderRuhr GREECE(EL) AgriculturalUniversityofAthens AristotleUniversity,Thessaloniki ChemicalProcessEngineeringResearchInstitute, ThermiThessaloniki HellenicCentreforMarineResearch,AnavissosAttiki InternationalQualityandEnvironmentServicesS.A., Athens InstituteofAcceleratingSystemsandApplications, Athens 287 VIROBATHE GABRIEL EMFNET GABRIEL SENSITIV NOMIRACLE,SENSITIV 2 GA LEN,SAFEFOODS CELLNANOTOX ENSEMBLES MICRODIS MONIQA,PHOEBE REPROTECT,SENSITIV CIRCE,ENSEMBLES, METHODEX ENSEMBLES ACUTETOX,REPROTECT PIONEER NANOSH CELLNANOTOX,HEIMTSA ENSEMBLES,ESPREME, DROPS,HEIMTSA,INTARESE, METHODEX GABRIEL REPROTECT FURANRA ATHON,FURANRA IMPART EMFNET NORMAN EUROPREVALL, SAFEFOODS CAIR4HEALTH,EMFNET, ENSEMBLES,NHRDEVTOX INTARESE CIRCE MONIQA CIRCE AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects InstituteofCommunicationandComputerSystems, Athens InstituteofChildHealth,Athens NationalandKapodistrianUniversityofAthens NationalCentreforScientificResearchDemokritos, AghiaParaskevi NationalHellenicResearchFoundation,Athens NationalObservatoryofAthens NationalTechnicalUniversityofAthens UniversityofCrete,Heraklion UniversityoftheAegean,Mytilene UniversityofPatras,PlataniPatras HUNGARY(HU) BudapestUniversityofTechnologyandEconomics CentralFoodResearchInstitute,Budapest EtzelMüszakiSzolgáltatóBt.,Budapest "FredericJoliotCurie"NationalResearchInstitutefor RadiobiologyandRadiohygiene,Budapest HospitaloftheHospitallerBrothersofStJohnofGod, Budapest HungarianAcademyofSciences,DepartmentofViral VaccinesandPathogenesis,Budapest HungarianAcademyOfSciences,Institutefor Sociology,Budapest “JohanBéla”NationalCentreforEpidemiology, Budapest JózsefFodorNationalCenterforPublicHealth, Budapest NationalInstituteofEnvironmentalHealth,Budapest SemmelweissUniversity,Budapest SzentIstvánUniversity,Budapest TheCleanAirActionGroup,Budapest UniversityofPécs 288 CIRCE PHIME CIRCE,EUROPREVALL, 2 GA LEN,INTARESE,PHOEBE HENVINET ECNIS,ESBIO,NEWGENERIS CIRCE,ENSEMBLES MONIQA CIRCE,EDEN,HIWATE, IMPART,NEWGENERIS CIRCE,HIWATE QALIBRA MONIQA SAFEFOODS ESPREME EMFNET EUROPREVALL EDEN SAFEFOODS EDEN ENVIE,EPIBATHE ECNIS,HEALTHYWATER, NEWGENERIS PIONEER EDEN METHODEX CASCADE AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects IRELAND(IE) ArchportLtd,Dublin AshtownFoodResearchCentre AthloneInstituteofTechnology,Athlone DublinInstituteofTechnology FoodSafetyAuthorityofIreland,Dublin GlantreoGlan,Cork Intel,Leixlip LendacDataSystemsLtd,Dublin MetEireann(CommunityClimateChangeConsortium forIreland),Dublin Medtronic,Galway NationalUniversityofIreland,Galway TrinityCollege,Dublin UniversityCollegeCork UniversityCollegeDublin ITALY(IT) ALTAsrl,Siena AntonDohrnZoologicalStation,Naples CatholicUniversityoftheSacredHeart,Milan CatholicUniversityofPiacenza CentreforAlpineEcology,Trento CERICOL,Sovignana CivicHospitalofBrescia CLUsrl,CastelfrancoEmilia ConsortiumforInformationSystems(CSI)Piemonte, Turin CSGI,SestoFiorentino EniEnricoMatteiFoundation,Milan EnvironmentParkSPA,Turin EuroMediterraneanCentreforClimateChange,Lecce GeneticsResearchInstitute&OspedalePoliclinics, Milano HylobatesConsultingSrl,Rome IDIhospital,Rome InstituteforAtmosphericPollutionResearch,Rende InstituteforScientificInterchangeFoundation,Torino 289 EXERA SAFEFOODS EXERA IMPART BENERIS NANOINTERACT NANOINTERACT BENERIS ENSEMBLES NANOINTERACT NANOINTERACT DEVNERTOX,NANOINTERACT EUROPREVALL,GABRIEL ACUTETOX, CARCINOGENOMICS, NANOINTERACT, PREDICTOMICS EXERA CRESCENDO 2FUN SAFEFOODS EDEN CELLNANOTOX EXERA CIRCE HENVINET NANOTOX CIRCE,ENSEMBLES, VERHICHILDREN NOMIRACLE CIRCE ECNIS HIWATE SENSITIV ESPREME ECNIS AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects InstituteofAtmosphericSciencesandClimate, Bolognaandotherlocations InstituteofBiometeorology,Florence InstituteofPharmacologicalResearchMarioNegri, Milan InstituteofSciencesofFoodProduction(ISPA),Rome InstituteofStudiesfortheIntegrationofSystems, Rome InteruniversitaryConsortiumforMagneticResonance ofParamagneticMetalloproteins,SestoFiorentino InteruniversityMarineBiologyandAppliedEcology Centre"G.Bacci"(CIBM),Livorno ItalianNationalAgencyforNewTechnologies,Energy andtheEnvironmentofItaly(ENEA),Rome ItalianNationalCentreforPreventionofHeatHealth Effects,Rome ItalianNationalInstituteforOceanographyand ExperimentalGeophysics,SgonicoTrieste ItalianNationalInstituteofGeophysicsand Volcanology,Bologna ItalianNationalReferenceCentreforVeterinary Epidemiology'G.Caporale',Teramo ItalianNationalHealthInstitute(ISS),Rome ItalianNationalResearchCouncil(CNR),Milan ItalianNationalResearchCouncil(CNR),Pisa ItalianNationalResearchCouncil(CNR),Rome ItalianNationalResearchInstituteforFoodand Nutrition(INRAN),Rome MagnaGræciaUniversity,Catanzaro MBNNanomaterialiaSPA,Carbonera MilanPolytechnicInstitute NationalInstituteforCancerResearch,Genoa NationalInstituteforOccupationalsafetyand Prevention,Rome RegionalEnvironmentalProtectionAgencyforEmilia Romagna(ARPA),Bologna RegionalEnvironmentalProtectionAgencyfor Lombardia(ARPA),Milan RomeEnvironmentalHealthAuthority SanCarloClinic,PadernoDugnano SecondUniversityofNaples SpallanzaniInstitute,Cremona UniversityofBologna UniversityofBrescia 290 CIRCE,ENSEMBLES,POLYSOA CIRCE ATHON,CAESAR,CASCADE, HIWATE,OSIRIS,RAINBOW MONIQA METHODEX EUROPREVALL ENVIE CIRCE,EMFNET,HENVINET, REPROTECT INTARESE CIRCE CIRCE,ENSEMBLES EDEN ACUTETOX,CASCADE, EDEN,EMFNET,FURANRA, OSIRIS,REPROTECT, SAFEFOODS,VIROBATHE EMFNET DIPNA EUROPREVALL,GA2LEN CASCADE,MONIQA DIPNA NANOTOX CAESAR,RAINBOW HENVINET,NEWGENERIS EMFNET ENSEMBLES ESBIO ENVIE,INTARESE EUROPREVALL CRESCENDO,MONIQA REPROTECT CIRCE,EMFNET,MONIQA PHIME AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects UniversityofCagliari UniversityofCa’Foscari,Venice UniversityofFlorence UniversityofGenoa UniversityofL'Aquila,Coppito UniversityofMilan UniversityofModenaandReggioEmilia UniversityofPalermo UniversityofParma UniversityofPavia UniversityofPiemonteOrientale"Amedeo Avogadro",Vercelli UniversityofPisa UniversityofRome'LaSapienza' UniversityofRome"TorVergata" UniversityofSalento,Lecce UniversityofSiena UniversityofTrieste UniversityofTuscia,Viterbo UniversityofUdine UniversityofVenice UniversityofVerona VeniceResearchConsortium(CVR) WaterResearchInstitute,Bari Zadigromasrl,Rome LATVIA(LV) LatvianSocietyofToxicology,Riga PVDFoodandVeterinaryService,Riga PublicHealthAgencyofLatvia,Riga LATVIA(LV)LITHUANIA(LT) CentreforCommunicableDiseasesPreventionand Control,Vilnius KaunasUniversityofMedicine KaunasUniversityofTechnology VilniusUniversity VytautasMagnusUniversity,Kaunas 291 EUROLYMPH 2FUN ENSEMBLES,MICRODIS, SENSITIV 2 EMFNET,GA LEN CIRCE CASCADE,CRESCENDO, ENVIE,EXERA,NOMIRACLE, SENSITIV DIPNA,HiWATE 2 GA LEN DEVNERTOX DEVNERTOX NOMIRACLE VIROBATHE EDEN,EMFNET,PIONEER SAFEFOODS,VIROBATHE CIRCE REPROTECT PHOEBE CIRCE,DIEPHY,FURANRA PHIME PARTICLE_RISK GABRIEL PARTICLE_RISK CIRCE CIRCE IMPART SAFEFOODS EDEN EDEN PHIME IMPART,NOMIRACLE EUROPREVALL HIWATE AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects LUXEMBOURG(LU) CELLONSA,Bereldange InitiativLiewensufankasbl,Itzig NETHERLANDS(NL) AcademicMedicalCentreofUniversityofAmsterdam Agrotechnology&Foodlnnovations,Ijmuiden AlterraBv,Wageningen BioDetectionSystemsBV,Amsterdam BioMaDeTechnologyFoundation,Groningen DelftUniversityofTechnology DSM,TeHeerlen DutchInstituteofFoodSafety(RIKILT),Wageningen EcobabyFoundation,Amsterdam EnvironmentHealthSciencesInternational(EHSI), Hulst ErasmusUniversityMedicalCentre,Rotterdam GroningenUniversityHospital HealthnetInternationalFoundation,Amsterdam InstituteofAppliedScientificResearch(TNO),Utrecht, Zeist,Leiden,Delft InVitroTestingIndustrialPlatform,Rotterdam KWRWatercycleResearchInstitute,Nieuwegein LeidenUniversity MaastrichtUniversity MinistryforHousing,SpatialPlanningand Environment,DenHaag NationalInstituteforPublicHealthandthe Environment(RIVM),Bilthoven 292 EXERA ESBIO 2 EUROPREVALL,GA LEN EUROPREVALL NOMIRACLE NEWGENERIS,REPROTECT IMPART BENERIS NANOINTERACT SAFEFOODS HENVINET ESBIO PHOEBE,REPROTECT EUROPREVALL MICRODIS CAESAR,CARCINOGENOMICS, GABRIEL,HEIMTSA, HENVINET,INTARESE, NANOSH,OSIRIS,REPROTECT ACUTETOX,RAINBOW, SENSITIV OSIRIS CARCINOGENOMICS, EUROPREVALL,GABRIEL, PREDICTOMICS CARCINOGENOMICS,ECNIS, EUROPREVALL,INTARESE, NEWGENERIS,SAFEFOODS PRONET BRAFO,FOOD&FECUNDITY, INTARESE,MONIQA, NANOINTERACT,NOMIRACLE, NORMAN,OSIRIS,RAINBOW, REPROTECT,RETHINK,SAFE FOODS,VIROBATHE AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects NetherlandsAnaphylaxisNetworkFoundation, Dordrecht NetherlandsEnvironmentalAssessmentAgency, Bilthoven PublicHealthServicesGelderlandMidden,Arnhem RadboudUniversity,Nijmegen RoyalNetherlandsMeteorologicalInstitute,DeBilt SanquinBloodSupplyFoundation,Amsterdam UniversityofGroningen UniversityofMaastricht UtrechtUniversity VUUniversity,Amsterdam WageningenUniversity POLAND(PL) BuildingResearchInstitute(ITB),Warsaw CentreforMedicalBiology,PolishAcademyof Medicine,ód CentralInstituteforLabourProtection– NationalResearchInstitute,Warsaw InstituteforEcologyofIndustrialAreas(IETU), Katowice lnstituteofAnimalReproductionandFoodResearch, Olsztyn InstituteofOccupationalMedicineand EnvironmentalHealth,Sosnowiec JagiellonianUniversityMedicalCollege,Cracow MedicalResearchCenter,PolishAcademyofSciences, Warsaw MedicalUniversityofBiaystok MedicalUniversityofód MedicalUniversityofSilesia,Katowice MedicalUniversityofWarsaw NationalFoodandNutritionInstitute,Warsaw NETIXSkrzypczynski,KrzysztofowiczSp.J.,Warsaw 293 EUROPREVALL ENSEMBLES,INTARESE HENVINET,PRONET NOMIRACLE ENSEMBLES EUROPREVALL GABRIEL EUROPREVALL ACUTETOX,CAIR4HEALTH, ECNIS,EDEN,EUROPREVALL, 2 GABRIEL,GA LEN,HEIMTSA, INTARESE,SAFEFOODS ATHON,CIRCE,FURANRA, NOMIRACLE,NORMAN, OSIRIS,PHOEBE,SENSITIV EUROPREVALL,HENVINET, NOMIRACLE,QALIBRA, OSIRIS,SAFEFOODS ENVIE NHRDEVTOX EMFNET,NANOSH DROPS,ESPREME,2FUN, PHIME EUROPREVALL PHIME 2 EUROPREVALL,GA LEN, NOMIRACLE NHRDEVTOX EDEN 2 EUROPREVALL,GA LEN DROPS ACUTETOX MONIQA ECNIS AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects NicolausCopernicusUniversity,CollegiumMedicumin Bydgoszcz NILUPolskaLtd.,Katowice NoferInstituteofOccupationalMedicine,ód PlantBreedingandAcclimatisationInstitute,Blonie ResearchCentreforAgriculturalandForest Environment,Poznan UniversityofWarsaw WroclawMedicalUniversity PORTUGAL(PT) AveiroUniversity InstituteofMechanicalEngineering,Lisbon LisbonFacultyofMedicine,PreventiveMedicine Instutute,EnvironmentalHealthUnit NewUniversityofLisbon,InstituteofTropicalHygiene andMedicine SPIPortugal,Porto UniversityofCoimbra UniversityofLisbon,FacultyofSciences UniversityofPorto ROMANIA(RO) DanubeDeltaNationalInstituteforResearch,Tulcea County InstituteofFoodBioresources,Bucharest InstituteofPhysicalChemistryI.G.Murgulescu, Bucharest NationalInstituteofHydrologyandWater Management,Bucharest NationalInstituteofResearchandDevelopmentof MicrobiologyandImmunology"Cantacuzino", Bucarest NationalInstituteofResearchandDevelopmentfor TechnicalPhysics,Iasi NationalMeteorologicalAdministration,Bucharest UniversityofCraiova 294 ECNIS DROPS,ESPREME,HEIMTSA DEVNERTOX,DIEPHY,ECNIS, ESBIO,IMPART, NANOINTERACT,NANOTOX, NHRDEVTOX,OSIRIS SAFEFOODS ENSEMBLES METHODEX,PHIME GABRIEL NOMIRACLE ENVIE ESBIO EDEN SAFEFOODS 2 GA LEN CIRCE,2FUN VIROBATHE EDEN HENVINET IMPART ENSEMBLES EDEN IMPART ENSEMBLES IMPART AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects SLOVAKIA(SK) EnvironmentalInstitute,Koš SlovakAcademyofSciences,InstituteofExperimental Endocrinology,Bratislava SlovakAcademyofSciences,DepartmentofMedical Zoology SlovakMedicalUniversity,Bratislava SlovakTechnicalUniversity,Bratislava WaterResearchInstitute,Bratislava SLOVENIA(SI) InstituteofPublicHealthoftheRepublicofSlovenia, Ljubljana JožefStefanInstitute,Ljubljana MedicalFacultyofLjubljana,InstituteofMicrobiology NationalInstituteofChemistry,Ljubljana RegionalAuthorityofPublicHealthBanskáBystrica UniversityMedicalCentre,Ljubljana SPAIN(ES) AdvancedInVitroCellTechnologies,Barcelona AssociationforResearchandIndustrialCooperationof AndalusiaF.dePaulaRojas"(AICIA),Sevilla AutonomousUniversityofBarccelona AutonomousUniversityofMadrid BarcelonaSciencePark CarlosIIIHealthInstitute,Madrid CatalanInstituteofNanotechnology,Barcelona CatalanInstituteofOncology,Barcelona CentreforEnergy,EnvironmentandTechnology Research(CIEMAT),Madrid CentreforGenomicRegulation,Barcelona CentreforResearchonEnvironmentalEpidemiology (CREAL),Barcelona ComplutenseUniversityofMadrid CMPCientificaSl,LasRozas 295 NORMAN CASCADE EDEN ENVIRISK,HEIMTSA, HENVINET,INTARESE, NEWGENERIS HENVINET NORMAN OSIRIS IMPART,NANOSAFE2, NORMAN,PHIME EDEN CAESAR ESBIO,PHIME PHIME ACUTETOX, CARCINOGENOMICS ENVIE NEWGENERIS 2 GA LEN CIRCE,INTARESE EDEN DIPNA ECNIS,EUROLYMPH, HIWATE ACUTETOX,EUROREVALL HIWATE HIWATE,NEWGENERIS CIRCE NANOTOX AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects FoundationforBiomedicalResearchatRamonyCajal UniversityHospital,Madrid FoundationforClimateResearch,Madrid FundaciónHospitalAlcorcon,Madrid FundaciónPrivadaparalaInvestigaciónNutricional, Barcelona GaikerFoundation,Zamudio(Bizkaia) HospitalClinicoSanCarlosdeMadrid InstituteofBiomedicalResearch,Barcelona InstituteofEarthSciences,Barcelona InVitroTestingIndustrialPlatform,TresCantos LaFeUniversityHospital,Valencia LaPazUniversityHospital,Madrid MediterraneanCentreforEnvironmentalStudies, Valencia MolecularDiagnosticsCenter,Orihuela MunicipalInstituteofMedicalResearch(IMIM), Barcelona NeikerTecnalia,theBasqueInstituteforAgricultural ResearchandDevelopment,Derio NosciraSA,Madrid PHARMAMAR,S.A.,ColmenarViejo PompeuFabraUniversity,Barcelona PolytechnicUniversityofCatalonia,Barcelona PublicHealthAgencyofBarcelona PrinceFelipeResearchCentre,Valencia ProgenikaBiopharma,S.A.,Derio ProteomikaS.L.,Derio Rovira&VirgiliUniversity,Reus ScientificWriting&ConsultancyS.C.,Pedreguer SimppleS.L.,Tarragona SpanishNationalInstituteofMeteorology,Madrid SpanishNationalResearchCouncil(CSIC),Barcelona SpanishNationalResearchCouncil(CSIC),Madrid SpanishNationalResearchCouncil(CSIC),Sevilla TechnicalUniversityofMadrid(UPM) TechnologicalInstitutefortheMarineEnvironment ControlofGalicia,VillagarciadeArousa UniversityofAlcaládeHenares,Madrid UniversityofBarcelona UniversityofCantabria,Santander 296 EUROPREVALL ENSEMBLES EUROPREVALL BENERIS ACUTETOX,MONIQA EUROPREVALL ACUTETOX CIRCE REPROTECT ACUTETOX, CARCINOGENOMICS, PREDICTOMICS EUROPREVALL CIRCE HEALTHYWATER GA2LEN,HIWATE,INTARESE EDEN ACUTETOX PREDICTOMICS PHOEBE CIRCE PRONET ATHON,DEVNERTOX PREDICTOMICS SENSITIV EPIBATHE,HEALTHYWATER, NOMIRACLE,OSIRIS SENSITIV OSIRIS ENSEMBLES INTARESE,NOMIRACLE CRESCENDO,NORMAN EDEN CIRCE CIRCE CIRCE ACUTETOX,EDEN, HEALTHYWATER, VIROBATHE ENSEMBLES AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects UniversityofCastillaLaMancha,Toledo UniversityofGranada UniversityofSantiagodeCompostela,Vigo UniversityoftheBalearicIslands,PalmadeMallorca UniversityoftheBasqueCountry,Leioa UniversityofValencia SWEDEN(SE) AxcentuaPharmaceuticals,Huddinge BiovitrumAB,Stockholm CellartisAB,Gothenburg EnvironmentalCompetenceABExpertrådet, Sollentuna FaciliaAB,Bromma KaroBioAB,Huddinge KarolinskaInstitute,Stockholm/Huddinge LeocordiaAB,Stockholm LundUniversity NationalFoodAdministration,Uppsala NationalInstituteforWorkingLife,Stockholm PhadiaAB,Uppsala RoyalInstituteofTechnology,Stockholm Scarab,Stockholm StockholmCountyCouncil StockholmUniversity SwedishEnvironmentalResearchInstitute, Gothenburg/Stockholm SwedishFundforResearchwithoutAnimal Experiments,Älvsjö SwedishInstituteforInfectiousDiseaseControl,Solna SwedishMeteorologicalandHydrologicalInstitute, Norrköping SwedishNationalTestingandResearchInstitute, Borås UniversityofGothenburg 297 ENSEMBLES CASCADE CIRCE CIRCE CIRCE ACUTETOX,EDEN CRESCENDO ACUTETOX CARCINOGENOMICS ACUTETOX 2FUN CASCADE,CRESCENDO ATHON,CASCADE, CRESCENDO,DIEHY,ECNIS, EMFNET,ESBIO,GABRIEL, INTARESE,NEWGENERIS, PHIME,PHOEBE,PIONEER, RAINBOW ECNIS ECNIS,ENSEMBLES, NANOINTERACT,PHIME, SENSITIV SAFEFOODS EMFNET EUROPREVALL ACUTETOX HIWATE PRONET ACUTETOX,DIEPHY, HENVINET,NEWGENERIS, NOMIRACLE,NORMAN, OSIRIS ESPREME ACUTETOX EDEN,HIWATE ENSEMBLES ENVIE 2 GA LEN,SAFEFOODS AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects UmeåUniversity ACUTETOX,ATHON, HENVINET,PHIME ACUTETOX,DEVNERTOX, REPROTECT UppsalaUniversity UNITEDKINGDOM(UK) AEATechnologyPlc,Didcot AnaphylaxisCampaign,FarnboroughHampshire BaigentLtd,Chesham BiomathematicsandStatisticsScotland,Edinburgh BuildingResearchEstablishment(BRE),Watford CampdenBRI,ChippingCampden CambridgeEconometricsLimited CentralManchesterandManchesterChildren's UniversityHospitalsNationalHealthServiceTrust CentralScienceLaboratory,York ChalexResearchLtd,StMarychurch CranfieldUniversity CyprotexPLC,Macclesfield CXRBiosciencesLTD,Dundee EcoTraceLimited,Camberley EMRC,Reading EnvironmentAgency,Rothley,Starcross FoodandEnvironmentResearchAgency,York FrancisCarpanini,Crownthorne HealthandSafetyExecutiveHealthandSafety Laboratory,Buxton HealthProtectionAgency,variouslocations HospitalityandLeisureManpower,KingstonUpon Thames ICConsultantsLtd,London ImperialCollegeofScience,TechnologyAndMedicine, London InstituteofCancerResearch,Sutton InstituteofFoodResearch,Norwich InstituteofOccupationalMedicine,Edinburgh IntrinsiqMaterialsLtd,Bristol IPPragmatics,TheLondonBioscienceInnovation Centre,London 298 METHODEX EUROPREVALL EUROPREVALL SAFEFOODS ENVIE MONIQA DROPS EUROPREVALL CAESAR,HENVINET, MONIQA,VIROBATHE NANOTOX ENVIE OSIRIS NHRDEVTOX FURANRA METHODEX NORMAN,VIROBATHE QALIBRA NHRDEVTOX NANOSAFE2,NANOSH ESBIO,INTARESE,VIROBATHE EUROPREVALL HIWATE,INTARESE BRAFO,CARCINOGENOMICS, ECNIS,EUROPREVALL, GABRIEL,HEIMTSA, HIWATE,INTARESE,PHOEBE, PIONEER,REPROTECT ECNIS EUROPREVALL,MONIQA, SAFEFOODS ESPREME,METHODEX, PARTICLE_RISK NANOSAFE2 EUROPREVALL AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects King'sCollegeLondon LancasterUniversity LHASALTD,Leeds LiverpoolJohnMooresUniversity LondonSchoolofEconomics LondonSchoolofHygieneandTropicalMedicine MetOffice,Exeter NapierUniversity,Edinburgh NationalPhysicalLaboratory,Teddington NationalRadiologicalProtectionBoard,Harwell NaturalEnvironmentResearchCouncil,Wallingford/ SwindonWiltshire NationalHeartandLungInstitute,London NaturalHistoryMuseum,London OxonicaLtd,Kidlington PaulWatkissAssociatesLtd,Oxford RothamstedResearchLimited,Harpenden ScottishCropResearchInstitute,Dundee SurfaceTherapeutics,Oxford TepnelBiosystemsLTD,Deeside UlsterUniversity,Coleraine UnileverUKCentralResourcesLimited,Sharnbrook UnitedBristolHealthcareNHSTrust UniversityCollegeLondon UniversityofAberdeen UniversityofBath UniversityofBirmingham UniversityofBradford UniversityofBristol UniversityofCambridge UniversityofDundee UniversityofEastAnglia,Norwich UniversityofEdinburgh UniversityofExeter UniversityofGlasgow UniversityofGreenwich UniversityofHertfordshire,Hatfield 299 EUROPREVALL,NOMIRACLE, SAFEFOODS NOMIRACLE NOMIRACLE CAESAR, CARCINOGENOMICS,OSIRIS, REPROTECT ENSEMBLES EDEN,ENSEMBLES,INTARESE CIRCE,ENSEMBLES PARTICLE_RISK NORMAN EMFNET CIRCE,NOMIRACLE 2 GA LEN EDEN NANOSAFE2 METHODEX EUROPREVALL SAFEFOODS GABRIEL EUROPREVALL NANOINTERACT,PHIME CARCINOGENOMICS, EUROPREVALL,SENSITIV ATHON,HENVINET NANOSAFE2 ACUTETOX HEIMTSA,METHODEX CIRCE,FURANRA EMFNET,NEWGENERIS ENSEMBLES,GABRIEL, PHOEBE NOMIRACLE ECNIS CIRCE,ENSEMBLES, EPIBATHE,EUROPREVALL, HEALTHYWATER, VERHICHILDREN PARTICLE_RISK HEIMTSA,OSIRIS NANOSAFE2 MICRODIS CAIR4HEALTH,ENVIRISK, HENVINET AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects UniversityofLeeds UniversityofLeicester UniversityofLiverpool UniversityofLondon,StGeorge's UniversityofManchester UniversityofNorthumbria,Newcastle UniversityofNottingham UniversityofOxford UniversityofReading UniversityofSouthampton UniversityofSurrey,Guildford UniversityofSussex,Brighton UniversityoftheWestofEngland,Bristol UniversityofWales,Aberystwyth UniversityofYork UKBiobankLtd,Stockport WessexInstituteofTechnology,Southampton WRcLtd,Swindon 300 EMFNET,NEWGENERIS ECNIS,NANOSH, NEWGENERIS,PHOEBE EDEN,ENSEMBLES, SENSITIV GABRIEL IMPART,NANOTOX MICRODIS ACUTETOX EDEN,ENSEMBLES,GABRIEL, NANOINTERACT, NANOSAFE2 ENSEMBLES CIRCE,EUROPREVALL, 2 GA LEN,NOMIRACLE,PHIME IMPART SAFEFOODS SENSITIV EPIBATHE,VIROBATHE CIRCE,EUROLYMPH,PHIME PHOEBE FOOD&FECUNDITY NOMIRACLE AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects COUNTRIESFROMOUTSIDETHEEUROPEANUNIONEUROPE CROATIA(HR) InstituteforMedicalResearchandOccupational Health,Zagreb OikonLtd.,Zagreb ICELAND(IS) LandspitaliUniversityhospital,Reykjavik NORWAY(NO) BiosenseLaboratoriesAS,Bergen CenterforInternationalClimateandEnvironmental Research,Oslo NorwegianFoodResearchInstituteMatforsk,Ås NansenEnvironmentalandRemoteSensingCentre, Bergen NationalVeterinaryInstitute,Oslo NorwegianInstituteforAirResearch(NILU),Kjeller NorwegianInstituteofPublicHealth,Oslo NorwegianMeteorologicalInstitute,Oslo NorwegianSchoolofVeterinaryScience,Oslo SwecoGrønerAs,Oslo UniversityofOslo RUSSIANFEDERATION(RU) A.N.BakhInstituteofBiochemistryoftheRussian AcademyofScience,Moscow InstituteofBiochemistry&Genetics,Ufa InstituteofMedicalGenetics,Tomsk MeteorologicalSynthesizingCentreEast,Moscow SiberianStateMedicalUniversity,Tomsk 301 ESBIO,HENVINET, NEWGENERIS PHIME EUROPREVALL NORMAN ENSEMBLES MONIQA,SAFEFOODS ENSEMBLES HENVINET,VIROBATHE DROPS,ENVIE,ENVIRISK, ESPREME,HEIMTSA, HENVINET,INTARESE NEWGENERIS,PHOEBE ENSEMBLES,HEIMTSA HENVINET HEIMTSA,METHODEX, MICRODIS ATHON,CRESCENDO, 2 ENSEMBLES,GA LEN, HENVINET,NEWGENERIS SAFEFOODS GABRIEL GABRIEL ESPREME,HEIMTSA EUROPREVALL,GABRIEL AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects SERBIA(RS) VincaInstituteofNuclearSciences,Belgrade SWITZERLAND(CH) CosmitalSA,Marly CSEMSA,Neuchatel FoundationforResearchonInformationTechnologies inSociety,Zürich GenedataAG,Basel InstituteforResearchinBiomedicine,Bellinzona InstituteofAllergyandAsthmaResearch,Zürich LausanneInstituteofTechnology(EPFL) NESTECSA,Vevey NestléResearchCentre,Lausanne PaulScherrerInstitute,Villingen Procter&GambleInternationalOperationsSa,Lancy SwissFederalOfficeofPublicHealth,Bern SwissFederalInstituteofTechnology,Zürich SwissFederalLaboratoriesforMaterialsTestingand Research,Dübendorf,StGallen SwissFederalOfficeofMeteorologyandClimatology, Zürich SwissiInstituteforthePromotionofSafetyand Security,Zürich TemasAgTechnologyandManagementServices, Arbon UniversityofGeneva UniversityofBasel UniversityofBern UniversityofFribourg UniversityofLausanne UniversityofZürich TURKEY(TR) EgeUniversityMedicalSchool,BornovaIzmir HacettepeUniversity,Ankara TubitakMarmaraResearchCenterFoodInstitute, GebzeKocaeli 302 DIEPHY,INTARESE SENSITIV DIPNA,NANOSAFE2 EMFNET CARCINOGENOMICS, NEWGENERIS SENSITIV 2 GA LEN NOMIRACLE EUROPREVALL FURANRA CIRCE,POLYSOA OSIRIS SAFEFOODS ENSEMBLES,HEIMTSA, NOMIRACLE,OSIRIS IMPART ENSEMBLES NANOSAFE2 IMPART CRESCENDO,ENSEMBLES GABRIEL CIRCE,ENSEMBLES,OSIRIS, POLYSOA ENSEMBLES ACUTETOX,CRESCENDO ACUTETOX,EUROPREVALL, PHIME EDEN EDEN,MONIQA MONIQA AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects COUNTRIESFROMOUTSIDETHEEUROPEANUNIONAFRICA ALGERIA(DZ) AssociationforResearchonClimateandEnvironment, Oran PasteurInstitute,Alger EGYPT(EG) AinShamsUniversity,Cairo CentreforEnvironmentandDevelopmentforArab RegionandEurope,Cairo GHANA(GH) RoguchiMemorialInstituteforMedicalResearch, Accra MOROCCO(MR) HassanIIAgroveterninaryInstitute,Rabat NationalInstituteofHygiene,Rabat SENEGAL(SN) PasteurInstitute,Dakar SenegaleseInstituteofAgriculturalResearch,Dakar SEYCHELLES(SC) MinistryofHealth,Victoria,Seychelles SOUTHAFRICA(ZA) CouncilforScientificandIndustrialResearch,Pretoria eThekwiniMunicipality,Durban 303 CIRCE EDEN MONIQA CIRCE EUROPREVALL EDEN EDEN EDEN EDEN PHIME SAFEFOODS HENVINET AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects TUNISIA(TN) NationalInstituteofMarineScienceandTechnology, Salammbo PasteurInstituteofTunis 304 CIRCE CIRCE AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects COUNTRIESFROMOUTSIDETHEEUROPEANUNIONAMERICAS ARGENTINA(AR) ArgentineanAssociationofDoctorsforthe HENVINET Environment(AAMMA),BuenosAires CANADA(CA) HealthCanada,Ottawa ATHON McGillUniversity,Montreal PHOEBE UniversityofMontreal PHOEBE ECUADOR(EC) UniversidadSanFranciscodeQuito GABRIEL MEXICO(MX) NationalInstituteforPublicHealthofMexico, HENVINET Cuernavaoa,Morelos UNITEDSTATESOFAMERICA(US) ColumbiaUniversity,NewYork ENSEMBLES RiceUniversity,Houston,Texas NANOINTERACT UniversityofRochester,NewYork PHIME 305 AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects COUNTRIESFROMOUTSIDETHEEUROPEANUNIONASIA BANGLADESH(BD) InternationalCentreforDiarrhoealDiseaseResearch, Dhaka INDIA(IN) AllergyAsthmaAssociates,Mysore IntegralUniversity,Lucknow JadavpurUniversity,Calcutta UniversityofDelhi VoluntaryHealthAssociationofIndia,NewDelhi INDONESIA(ID) InstitutePertanianBogor,Bogor UniversityofIndonesia,Depok ISRAEL(IL) AnalystResearchLaboratoryLtd,Rehovot BenGurionUniversityoftheNegev,BeerSheva HebrewUniversityofJerusalem NanoPowdersIndustries(Israel)Ltd.,Caesarea OSMDANLtd,Rehovot TechnionIsraelInstituteofTechnology,Haifa TelAvivUniversity TheVolcaniCenter,BetDagan UniversityofHaifa VocaltagLtd,MigdalHaemek WeizmannInstituteofScience,Rehovot PAKISTAN(PK) TheAgaKhanUniversity,Karachi 306 PHIME EUROPREVALL HENVINET MICRODIS MICRODIS MICRODIS MONIQA MICRODIS FOOD&FECUNDITY CIRCE CIRCE IMPART FOOD&FECUNDITY ENVIRISK CELLNANOTOX,CIRCE FOOD&FECUNDITY CIRCE MONIQA NANOINTERACT PIONEER AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects PEOPLE'SREPUBLICOFCHINA(CN) BeijingUniversity ChineseAcademyofAgriculturalSciences, InstituteofCropGermplasmResources,Beijing ChineseCerealsandOilsAssociation,Beijing ChineseNationalInstituteofNutritionandFood Safety,Beijing ChineseUniversityofHongKong FudanUniversity,Shanghai SichuanUniversity,Chengdu PHILIPPINES(PH) Citizens'DisasterResponseCenterFoundation, QuezonCity XavierUniversity,CagayanDeOroCity SINGAPORE(SG) GenomeInstituteofSingapore SYRIA(SY) InternationalCentreforAgriculturalResearchinthe DryAreas,Aleppo VIETNAM(VN) HanoiSchoolofPublicHealth HanoiUniversityofTechnology HueUniversity,HueCity 307 HENVINET SAFEFOODS MONIQA SAFEFOODS EUROPREVALL,GABRIEL PHIME MONIQA MICRODIS MICRODIS CRESCENDO CIRCE MICRODIS MONIQA MICRODIS AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects COUNTRIESFROMOUTSIDETHEEUROPEANUNIONAUSTRALIAAND OCEANIA AUSTRALIA(AU) BureauofMeteorologyResearchCentre,Melbourne NEWZEALAND(NZ) InstituteofEnvironmentalScienceandResearch, Christchurch 308 ENSEMBLES MONIQA AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects INTERNATIONALORGANISATIONS EUROPEANUNION(EU) EuropeanCommission,JointResearchCentre(JRC), Ispra ACUTETOX,CAIR4HEALTH, CARCINOGENOMICS, CELLNANOTOX,CIRCE,DIPNA, EMFNET,ENSEMBLES,ENVIE, 2FUN,GABRIEL,HEIMTSA, HENVINET,MONIQA, NOMIRACLE,NORMAN,OSIRIS, PREDICTOMICS,REPROTECT, SENSITIV ORGANISATIONFORECONOMICCOOPERATIONAND DEVELOPMENT(OECD) EnvironmentDirectorate TESTMETEDECO, VERHICHILDREN UNITEDNATIONS(UN) InternationalAgencyforResearchonCancer,Lyon AbdusSalamInternationalCentreforTheoretical Physics,Trieste UnitedNationsOfficefortheCoordinationof HumanitarianAffairs,NewYork WorldHealthOrganization,Geneva,Rome EMFNET,ECNIS,EUROLYMPH ENSEMBLES MICRODIS CIRCE,EMFNET,EPIBATHE, HENVINET,INTARESE OTHERINTERNATIONALORGANISATIONS EuropeanAcademyofAllergologyandClinical GA2LEN Immunology(EAACI),Brussels EuroAEGISEuropeanAgroEnvironmentalHealth EDEN Associates,Zoersel EuropeanBioinformaticsInstitute,Cambridge CARCINOGENOMICS EuropeanCentreforMediumRangeWeather ENSEMBLES Forecasts,Reading EuropeanChemicalIndustryCouncil(CEFIC),Brussels INTARESE 309 AnnexA ParticipatingCountriesandInstitutesinFP6FundedEnvironmentAnd HealthProjects EuropeanConsensusPlatformon3RAlternativesto AnimalExperimentation(ECOPA),Brussels EuropeanCosmeticToiletryandPerfumery Association(COLIPA),Brussels EuropeanFederationofAllergyandAsthmaPatients Associations(EFA),Brussels EuropeanFoodInformationCouncil,Brussels EuropeanMolecularBiologyLaboratory(EMBL), Heidelberg EuropeanOilCompanyOrganisationforEnvironment, HealthandSafety(CONCAWE),Brussels EuropeanTechnicalTradeUnionOfficeforHealthand Safety,Brussels EuropeanTelecommunicationNetworkOperators' Association(ETNO),Brussels GsmAssociation,London ILSIEurope,Brussels InternationalCommissiononNonIonizingRadiation Protection,Oberschleissheim InternationalGlobalEthicsAssociationIgea,Ghent MobileManufacturersForum,Brussels UnionoftheElectricityIndustryEurelectric,Brussels 310 CARCINOGENOMICS, PREDICTOMICS,SENSITIV SENSITIV EUROPREVALL,GA2LEN SAFEFOODS CRESCENDO ESBIO EMFNET EMFNET EMFNET BRAFO EMFNET EMFNET EMFNET EMFNET AnnexB– VariousIssuesAddressedbyFP6Projects AnnexB Variousissues addressedbyFP6projects Explanationofsymbolsused: Projectrelatedto:Chemicals[ foodallergens[ [ ];Ambientairpollutants[)],Environmental/ ],Indoorairpollutants[]],Climaticfactors[¾],Extremeevents ],Nanoparticles[],Microbialagents[×],Ultravioletradiation[Ò],Ionising radiation[ ],Nonionisingradiation[ª],Noise[],Pharmaceuticals[ ],waste [ ] Projectaddressinghorizontal/crosscutting/coordinatingissues[4] Project of some relevance to environment and health research and/or policy making,butinwhichhealthorenvironmentalaspectsareminor[Ä] Whentherearetwosymbols,theprojectaddressestwoissues,thefirstofwhichis consideredtobethemajorfocusoftheproject 311 312 AnnexB–VariousIssuesAddressedbyFP6Projects Support,toolsandmethodsdevelopmentfor environmentandhealth 313 314 AnnexB–VariousIssuesAddressedbyFP6Projects Reviewofknowledge, Nb projects 27 Projectacronyms [4]:CAIR4HEALTH,HENVINET,PHOEBE coordination, [4,]]:ENVIE metaanalysis [4,ª]:EMFNET [4,]:IMPART [4,],]:PRONET [4, [4, [ ]:RAINBOW,ECNIS,ESBIO ,×,)]:GA2LEN ]:BRAFO,CARCINOGENOMICS, CASCADE,NHRDEVTOX,QALIBRA, TESTMETEDECO [), ]:ENVIRISK [), , [4, , [), ,]]:DROPS ]:METHODEX , ,Ä]:NORMAN [ ]:EUROPREVALL [ ,),],¾,]:HEIMTSA [ ,),],¾, [¾,×]:EDEN , Ò]:INTARESE [¾]:ENSEMBLES Databaseandinventory building 27 [ ]:MICRODIS [4]:HENVINET,PHOEBE [4, ]:ECNIS,ESBIO [4,],]:PRONET [4, ,×,)]:GA2LEN [ ]:ATHON,CARCINOGENOMICS, CASCADE,NEWGENERIS,OSIRIS,REPROTECT, SENSITIV [ ,Ä]:PIONEER [ ,×]:SAFEFOODS [), ,]]:DROPS [), ]:ENVIRISK [ [), ]:EUROPREVALL ,¾]:2FUN [¾,×]:EDEN [¾]:ENSEMBLES 315 AnnexB–VariousIssuesAddressedbyFP6 Projects [ ]:MICRODIS [ [), ,×,)]:GABRIEL , ]:METHODEX [4, , , ,Ä]:NORMAN []:DIPNA,NANOINTERACT Invitromethods, intelligenttesting, alternativetesting methods 22 ]:ACUTETOX,CAESAR, [ CARCINOGENOMICS,DEVNERTOX,EXERA, NHRDEVTOX,OSIRIS,PREDICTOMICS, REPROTECT,RETHINK,SENSITIV, TESTMETEDECO [ [4, ,Ä]:PIONEER ]:RAINBOW [ ]:FOOD&FECUNDITY []:CELLNANOTOX,NANOINTERACT, NANOSAFE2,NANOSH,PARTICLE_RISK [4,]:IMPART [)]:POLYSOA Biomarkers 17 ]:ATHON,CASCADE,DEVNERTOX, [ FURANRA,NEWGENERIS,PHIME, PREDICTOMICS [ ,Ä]:PIONEER [), ]:DIEPHY,ENVIRISK [4, ]:ECNIS,ESBIO [ ,×,)]:GABRIEL [ ,),],¾,]:HEIMTSA [ ,),],¾, []:DIPNA [4, 'omics' 17 , , Ò]:INTARESE , ,Ä]:NORMAN ]:ATHON,CARCINOGENOMICS, [ CASCADE,NEWGENERIS,NHRDEVTOX, OSIRIS,PHIME,FURANRA,PREDICTOMICS, REPROTECT,SENSITIV ]:ECNIS [4, []:CELLNANOTOX,DIPNA [ ,×,)]:GABRIEL [ ,Ä]:PIONEER [Ä]:CRESCENDO 316 AnnexB–VariousIssuesAddressedbyFP6Projects Standardisation/ validation/ harmonisationof methods 14 ]:ESBIO,ECNIS [4, [ ]:ACUTETOX,CARCINOGENOMICS, CASCADE,PHIME,PREDICTOMICS, REPROTECT,TESTMETEDECO [), , ]:METHODEX [4, , , ,Ä]:NORMAN []:DIPNA,NANOINTERACT [×]:HEALTHYWATER Goodpractices, guidelines 11 [ ]:BRAFO,QALIBRA [), [4, ]:DIEPHY ,×,)]:GA2LEN [ ,),],¾,]:HEIMTSA [ ,),],¾, , Ò]:INTARESE [¾,×]:EDEN [4,],]:PRONET []:DIPNA,NANOSAFE2 [4,]:IMPART Analyticalmethods, diagnostictools, therapeutics 9 [ ]:CASCADE,NEWGENERIS [ ]:EUROPREVALL [ ,×,)]:GABRIEL [4, ,×,)]:GA LEN [×]:HEALTHYWATER []:NANOSAFE2,NANOSH [)]:POLYSOA 2 Geographical informationsystems, spatialmodelling, remotesensing, earthobservation 9 [ ]:OSIRIS,PHIME [), ]:ENVIRISK [¾,)]:CIRCE [¾,×]:EDEN , [4, , ,Ä]:NORMAN [ ,),],¾,]:HEIMTSA [ ,),],¾, [ , 317 , Ò]:INTARESE , ),],¾, ,×]:NOMIRACLE AnnexB–VariousIssuesAddressedbyFP6Projects Environmentandhealth informationsystems, decisionsupport systems Risk/benefit analysis/methodsof food/environmental contaminants 3 [4]:HENVINET [ [), 7 [ [), [ 318 ]:OSIRIS ]:ENVIRISK ]:BENERIS,BRAFO,PHIME,QALIBRA ]:ENVIRISK ,×]:SAFEFOODS,HIWATE AnnexB–VariousIssuesAddressedbyFP6Projects Hazardidentification 319 320 AnnexB–VariousIssuesAddressedbyFP6Projects Epidemiology,cohorts, populationstudies, biobanking Nb projects 23 Projectacronyms [4]:PHOEBE [4, ]:ECNIS,ESBIO [4, ,Ò]:EUROLYMPH [4,ª]:EMFNET [4, [ [), ,×,)]:GA2LEN ]:BENERIS,NEWGENERIS,PHIME ]:DIEPHY [ ,Ä]:PIONEER [ ,×]:HIWATE [ ]:FOOD&FECUNDITY [×]:EPIBATHE,VIROBATHE [¾,)]:CIRCE [¾,×]:EDEN [ ]:MICRODIS [×]:HEALTHYWATER Transgenicanimals 9 [ ]:EUROPREVALL [ ,×,)]:GABRIEL [ ,),],¾,]:HEIMTSA [ ,),],¾, , Ò]:INTARESE ]:CASCADE,DEVNERTOX,EXERA, [ NHRDEVTOX,REPROTECT,SENSITIV [ ,Ä]:PIONEER ,×,)]:GABRIEL [ [Ä]:CRESCENDO Ecotoxicology 7 QSAR(Quantitative StructureActivity Relationship)modelling, insilico models/screening Epigenetics 6 ]:CAESAR,CASCADE,OSIRIS, [ TESTMETEDECO []:NANOINTERACT,NANOSAFE2 [4, , ,Ä]:NORMAN ]:ACUTETOX,CAESAR, [ CARCINOGENOMICS,CASCADE,OSIRIS [), 2 , ,¾]:2FUN ]:FURANRA [ [Ä]:CRESCENDO 321 322 AnnexB–VariousIssuesAddressedbyFP6Projects Exposureassessment 323 324 AnnexB – VariousIssuesAddressedbyFP6Projects Exposureassessment Nb projects 38 Projectacronyms ]:ATHON,BENERIS,BRAFO,CASCADE, [ DEVNERTOX,FURANRA,NEWGENERIS, OSIRIS,PHIME [ ,Ä]:PIONEER [), ]:DIEPHY,ENVIRISK,ESPREME [), ,]]:DROPS [4, ]:ESBIO,ECNIS [4,]:IMPART [4, ,Ò]:EUROLYMPH [), ,¾]:2FUN [ ,×]:HIWATE [¾]:ENSEMBLES []:CELLNANOTOX,DIPNA,NANOINTERACT, NANOSAFE2,NANOSH,PARTICLE_RISK [ ]:FOOD&FECUNDITY [×]:EPIBATHE,VIROBATHE [ ]:EUROPREVALL ,×,)]:GABRIEL [4, ,×,)]:GA2LEN [ [ ,),],¾,]:HEIMTSA [ ,),],¾, [), , , Ò]:INTARESE ]:METHODEX , , ),],¾, [ [4,],]:PRONET 325 ,×]:NOMIRACLE AnnexB – VariousIssuesAddressedbyFP6Projects Cumulativeexposure, mixtureissues, combinedexposure, chemicalcocktails Occupationalexposures 10 8 ]:ATHON,CASCADE,DEVNERTOX, [ NEWGENERIS,PHIME [), ]:DIEPHY [), ,¾]:2FUN [ ,),],¾,]:HEIMTSA [ ,),],¾, [ , [ ]:PHIME , Ò]:INTARESE , ),],¾, ,×]:NOMIRACLE [4, ]:ECNIS [4,]:IMPART []:DIPNA,NANOSAFE2,NANOSH [4,ª]:EMFNET [ (Bio)monitoring, surveillance 7 [4, [ ,×,)]:GABRIEL ]:ESBIO ,),],¾, [¾,×]:EDEN , Ò]:INTARESE [ ]:MICRODIS [×]:HEALTHYWATER [ [4, 326 ,×]:HIWATE , , ,Ä]:NORMAN AnnexB–VariousIssuesAddressedbyFP6Projects Healthimpactassessment 327 328 AnnexB – VariousIssuesAddressedbyFP6Projects Nb projects Cost/benefitanalysis, 11 economicvaluation, lifecyclecosting, burdenofdisease Projectacronyms [4]:VERHICHILDREN ]:OSIRIS,QALIBRA [ [), ,]]:DROPS [), ]:ENVIRISK,ESPREME [ ,),],¾,]:HEIMTSA [ ,),],¾, [), [ [ Integratedassessment tools/models, healthimpact assessment(HIA) 8 , ]:METHODEX ]:EUROPREVALL ]:MICRODIS [), ,]]:DROPS [), ]:ENVIRISK [¾,)]:CIRCE [ ]:MICRODIS [), Emissionfactors, inventories , Ò]:INTARESE 5 ,¾]:2FUN [ ,),],¾,]:HEIMTSA [ ,),],¾, [ , [), ,]]:DROPS [), ]:ESPREME [ , Ò]:INTARESE , ),],¾, ,×]:NOMIRACLE ,),],¾,]:HEIMTSA [), , ]:METHODEX [)]:POLYSOA Fullchain(impact pathway)approach 5 [), [), 2 ,¾]:2FUN [ ,),],¾,]:HEIMTSA [ ,),],¾, [), Lifecycleassessment (LCA) ,]]:DROPS , , Ò]:INTARESE ]:METHODEX [), , ]:METHODEX []:NANOSAFE2 329 330 AnnexC EnvironmentalFactors(Stressors)AddressedbyFP6Projects AnnexC Environmentalfactors(stressors) addressedbyFP6projects Explanationofsymbolsused: Projectrelatedto:Chemicals[ foodallergens[ [ ];Ambientairpollutants[)],Environmental/ ],Indoorairpollutants[]],Climaticfactors[¾],Extremeevents ],Nanoparticles[],Microbialagents[×],Ultravioletradiation[Ò],Ionising radiation[ ],Nonionisingradiation[ª],Noise[],Pharmaceuticals[ ],waste [ ] Projectaddressinghorizontal/crosscutting/coordinatingissues[4] Project of some relevance to environment and health research and/or policy making,butinwhichhealthorenvironmentalaspectsareminor[Ä] Whentherearetwosymbols,theprojectaddressestwoissues,thefirstofwhichis consideredtobethemajorfocusoftheproject 331 332 AnnexCEnvironmentalFactors(Stressors)AddressedbyFP6Projects Stressor Nbprojects Projectacronyms Chemicalpollution Environmental andfoodchemical contaminants 37 [ ]:ACUTETOX,ATHON,BENERIS,CAESAR CARCINOGENOMICS,CASCADE,DEVNERTOX, EXERA,FURANRA,NEWGENERIS,NHRDEVTOX, OSIRIS,PHIME,QALIBRA,REPROTECT,RETHINK, SENSITIV,TESTMETEDECO [ ,Ä]:PIONEER [ ,×]:HIWATE,SAFEFOODS [ , ]:PREDICTOMICS [4, ]:ECNIS,ESBIO , ,Ä]:NORMAN [4, , [), ]:DIEPHY,ENVIRISK,ESPREME [), ,]]:DROPS [), , [4, ,Ò]:EUROLYMPH [), ,¾]:2FUN ]:METHODEX ]:RAINBOW [4, [ ,),],¾,]:HEIMTSA [ ,),],¾, , Ò]:INTARESE , , ),],¾, [ [4]:HENVINET Pharmaceutical products 5 [ [ ]:FOOD&FECUNDITY,RETHINK , [4, [ Ultrafineparticles Nanoparticles, ultrafineparticles 10 ,×]:NOMIRACLE ]:PREDICTOMICS , , , ,Ä]:NORMAN , ),],¾, ,×]:NOMIRACLE []:CELLNANOTOX,DIPNA,IMPART, NANOINTERACT,NANOSAFE2,NANOSH, PARTICLE_RISK [4,]:IMPART , , ,Ä]:NORMAN [4, [4]:HENVINET 333 AnnexCEnvironmentalFactors(Stressors)AddressedbyFP6Projects Waste Exposuretowaste 3 [), , ]:METHODEX ,),],¾, , Ò]:INTARESE , , ),],¾, ,×]:NOMIRACLE [ Airpollution Ambientair pollutants [ 16 ) [4]:CAIR4HEALTH,HENVINET [4, ]:ECNIS [)]:POLYSOA [), ]:DIEPHY,ENVIRISK,ESPREME [), ,]]:DROPS [), ,¾]:2FUN [), , ]:METHODEX [¾,)]:CIRCE ,×,)]:GABRIEL [4, ,×,)]:GA2LEN [ Indoorairquality andcontaminants 8 ] [ ,),],¾,]:HEIMTSA [ ,),],¾, , Ò]:INTARESE , , ),],¾, [ [4,]]:ENVIE [4,],]:PRONET [), ,]]:DROPS ,×,)]:GABRIEL [4, ,×,)]:GA2LEN [ [ ,),],¾,]:HEIMTSA [ ,),],¾, [ , [ ]:EUROPREVALL , Ò]:INTARESE , ),],¾, Allergeniccompounds Environmental/ foodallergens ,×]:NOMIRACLE 3 [ [4, ,×,)]:GABRIEL ,×,)]:GA2LEN 334 ,×]:NOMIRACLE AnnexCEnvironmentalFactors(Stressors)AddressedbyFP6Projects Microbialpathogenicagents Microbial 9 pathogens × [×]:EPIBATHE,HEALTHYWATER,VIROBATHE [¾,×]:EDEN [ ,×]:HIWATE,SAFEFOODS ,×,)]:GABRIEL [4, ,×,)]:GA2LEN [ , [ Radiation Nonionising radiation(EMF) ª Ultraviolet radiation 1 1 , ),],¾, ,×]:NOMIRACLE [ª,4]:EMFNET ,),],¾, [ , Ò]:INTARESE Ò Environmentalnoise Coexposureto noiseandother stressors 1 ,),],¾,]:HEIMTSA [ Globalchange Climatechange, climatefactors, globalwarming 8 [¾]:ENSEMBLES [¾,)]:CIRCE [¾,×]:EDEN ¾ [), ,¾]:2FUN [ ,),],¾,]:HEIMTSA [ ,),],¾, , Ò]:INTARESE , , ),],¾, [ [4]:HENVINET Extremeevents Extremeevents 1 [ ]:MICRODIS *canbethemainfocusorpartiallyaddressed 335 ,×]:NOMIRACLE 336 AnnexD – HealthEndpointsAddressed byFP6Projects AnnexD HealthendpointsaddressedbyFP6projects Explanationofsymbolsused: Projectrelatedto:Chemicals[ foodallergens[ [ ];Ambientairpollutants[)],Environmental/ ],Indoorairpollutants[]],Climaticfactors[¾],Extremeevents ],Nanoparticles[],Microbialagents[×],Ultravioletradiation[Ò],Ionising radiation[ ],Nonionisingradiation[ª],Noise[],Pharmaceuticals[ ] Projectaddressinghorizontal/crosscutting/coordinatingissues[4] Project of some relevance to environment and health research and/or policy making,butinwhichhealth(orenvironmental)aspectsareminor[Ä] Whentherearetwosymbols,theprojectaddressestwoissues,thefirstofwhichis consideredtobethemajorfocusoftheproject 337 338 AnnexD–HealthEndpointsAddressed byFP6Projects Endpoint Nb projects 18 Cancer,genotoxicand mutageniceffects Projectacronyms ]:ATHON,CAESAR, [ CARCINOGENOMICS,CASCADE,FURANRA, NEWGENERIS [), ]:DIEPHY [4, ,Ò]:EUROLYMPH [4, ]:ECNIS [ ,×]:HIWATE []:CELLNANOTOX,DIPNA, NANOINTERACT,NANOSH,PARTICLE_RISK [ª,4]:EMFNET [4,]]:ENVIE [4]:HENVINET (Neuro)developmental disordersand/or neurogenerativediseases, mentaldisease, CNStoxicity, behavioural/neuro endocrineeffects Reproductionand reproductivedisordersand toxicity,impairmentof fertility 13 ]:ACUTETOX,ATHON,CAESAR, [ CASCADE,DEVNERTOX,NHRDEVTOX, PHIME,TESTMETEDECO [ [ ,×]:HIWATE [Ä]:CRESCENDO [ª,4]:EMFNET [4]:HENVINET 11 ]:ATHON,CAESAR,CASCADE, [ REPROTECT,TESTMETEDECO ]:FOOD&FECUNDITY [ [ª,4]:EMFNET [4]:HENVINET [ ,Ä]:PIONEER ,Ä]:PIONEER [ ,×]:HIWATE [Ä]:CRESCENDO 339 AnnexD–HealthEndpointsAddressedbyFP6Projects Respiratorydiseases includingallergy,asthma; lungtoxicity 11 [4,]]:ENVIE [4]:HENVINET [)]:POLYSOA ]:EUROPREVALL [ [ [4, ,×,)]:GABRIEL ,×,)]:GA2LEN [ ]:SENSITIV []:CELLNANOTOX,NANOSH, PARTICLE_RISK [¾]:ENSEMBLES Immunesystemeffects 7 ,×,)]:GABRIEL [4, ,×,)]:GA2LEN [ ]:NEWGENERIS [ [ª,4]:EMFNET Infectiousdiseases 6 [ ]:SENSITIV []:CELLNANOTOX,DIPNA [×]:EPIBATHE,HEALTHYWATER [¾]:ENSEMBLES [¾,)]:CIRCE [¾,×]:EDEN [ Cardiovasculardisease, metabolicdisorders, obesity,diabetes,stroke 5 Kidney(renal)toxicity 4 Liver(hepatic)toxicity 4 ]:MICRODIS [ ]:CASCADE,PHIME [ª,4]:EMFNET [4,]]:ENVIE [¾]:ENSEMBLES ]:ACUTETOX,PHIME,PREDICTOMICS [ []:CELLNANOTOX ]:ACUTETOX,FURANRA, [ PREDICTOMICS []:CELLNANOTOX 340 AnnexD–HealthEndpointsAddressedbyFP6Projects 2 [¾,)]:CIRCE [¾]:ENSEMBLES Effectsofaudition,hearing 1 [ª,4]:EMFNET Bonetoxicity 1 Digestivesystemtoxicity Vascularsystem, endothelialcell functioning Thyroiddisease 1 1 Generalmortality 1 ]:PHIME [ []:CELLNANOTOX []:NANOSH [ ]:ATHON Pleasenotethatotherprojectsalsoaddressvarioushealthendpointsbuttheirexact naturearecurrentlynotyetknownorwillbedeterminedduringthecourseofthe project. 341 European Commission EUR 25409 — European Research on Environment and Health Funded by the Sixth Framework Programme Snapshots of final results 67$",( " :);: Q @T1 Q ;T.* 7 :; $ <+ + 978-92-79-22211-5 ;);*=>>?@ 10.2777/19018 How to obtain EU publications Free publications: a SF>#2 LLHPELMEQQM?LLHPELMBROLM>BR a >QQEB#ROLMB>K2KFLK|POBMOBPBKQ>QFLKPLOABIBD>QFLKP6LR@>KL?Q>FKQEBFO@LKQ>@QABQ>FIPLKQEB 'KQBOKBQEQQMB@BROLM>BRLO?VPBKAFKD>C>UQL Priced publications: a SF>#2 LLHPELMEQQM?LLHPELMBROLM>BR a SF>LKBLCQEBP>IBP>DBKQPLCQEBÅR?IF@>QFLKP-ȵ@BLCQEB#ROLMB>K2KFLK EQQMMR?IF@>QFLKPBROLM>BRLQEBOP>DBKQPFKABU<BKEQJ EUROPEAN COMMISSION Directorate-General for Research and Innovation Directorate I – Environment Unit I.4 – Climate Change and Natural Hazards E-mail: [email protected] Contact: Tuomo Karjalainen European Commission B-1049 Brussels E-mail: [email protected] [email protected] EuropeanResearchOnEnvironment&HealthFundedByFP6 COVER PgsLim 06 indd 4-6 KINA25049ENC_001.pdf 2 1/06/12 11:58 25/07/12 10:50 Project information European Research on Environment and Health Funded by the Sixth Framework Programme Snapshots of final results KI-NA-25-049-EN-C Sixty-six multidisciplinary pan-European research projects dealing with environment and health issues were funded by the European Commission’s Research Directorate- General (now called DG Research and Innovation) in the Sixth Framework Programme of Research (20022006). The main results are presented in this catalogue. All of these projects have now ended and have produced a wealth of new and interesting results that have improved the science base and that have the potential to support various EU policies. The projects presented addressed a multitude of issues ranging from health impacts of climate change to improved integrated environment and health risk assessment methodologies. This overview should be useful to many stakeholders policy makers at national, EU and global level. European Research on Environment and Health Funded by the Sixth Framework Programme Research and Innovation EuropeanResearchOnEnvironment&HealthFundedByFP6 COVER PgsLim 06 indd 1-3 KINA25049ENC_001.pdf 1 1/06/12 11:58 25/07/12 10:50
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