Alternative Non-Testing methods Assessed for REACH Substances

www.antares-life.eu

Introduction to the Project

Alternative Non-Testingmethods Assessed forREACH Substances

www.antares-life.eu

info@antares-life.eu

Contents

03 TheLIFE+ProjectANTARES

04 REACHandNon-TestingMethods

06 ANTARESWebPortalOverview

07 ThesectionsoftheWebPortal

10 ProjectBeneficiaries

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The PROJECT

The LIFE+ Project ANTARES

The REACH legislation requires that all chemicals present in the European market in an amount higher than 1 t/year have suitable safety information

EC REGULATION NO 1907/2006 - Registration, Evaluation, Authorisation and restriction of CHemicals

REACH states that Non-Testing Methods (NTM)can be used to fulfill this requirement

Before making an animal experiment theindustryshouldverifyifalternative methodsexist.

The NTM methods are examples of alternativemethodswhichpredicttheeffectsofchemicalswithouttheuseoftherealcompound,butonlyonthebasisofthecompoundstructure.TheyincludeQuantitative Structure-Activity Rela-tionship (QSAR) modelsandRead-Across.

However, so far there isa gap of knowledgeonwhich methods are available and can be usedinpractice. 

The ANTARES project aims to reduce this gap assessing NTM as an alternative approach for the REACH legislation.

TheMAIN OBJECTIVES of ANTARES are:

• toverifythepossibleUSEandPERFOMANCEoftheNTMforREACH;

• toidentifyREQUIREMENTSandCONSTRAINTSoriginatingfromtheREACHlegislation;

• toidentifySAFETYASSESSMENTFACTORSfortheNTM;

• toidentifytheBESTAPPLICABILITYforasaferuseoftheNTM;

• toINTEGRATEDIFFERENTNTMachievingsuperiorperfomance;

• toDISSEMINATEtheresults;

• toPROMOTENTMforlegislativepurposes.

ThemainresultwillbeaCHARACTERIZATIONoftheNON-TESTINGMETHODSsuitablefor REACH

The ACTIONS

ANTARESisorganizedin13 Actions:

Action 1Survey of current methods for compliance toREACHlegislation

Action 2Identificationofcriteriafornon-testingmethodsforREACHlegislation

Action 3Identification of suitable experimental databas-es/data sets for ecotoxicological, toxicologicalandenvironmentalendpoints

Action 4List of (Q)SAR models for ecotoxicological,toxicological and environmental endpoints forREACH,andtheirreview

see Page 8

Action 5Validationofnon-testingmethods

Action 6Identification of boundaries for best use ofmodels(applicabilitydomain)andoftheassess-mentfactors

Action 7Architectureforintegrationofdifferentnon-test-ing methods for best performances and cover-ageofapplicability

Action 8 CommunicationandDissemination

Action 9 WebPortalsee Pages 6-9

Action 10 ProjectManagement

Action 11 Monitoring

Action 12 Audit

Action 13 After-LIFECommunicationplan

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REACH and NON-TESTING METHODS

REACH and NON-TESTINGMETHODS

This Regulation should ensure a high level of protection of human health and the environment as well as the free movement of substances inpreparations and in articles, while enhancing competitiveness and innovation. This Regulation should also promote the development of alternative methods fortheassess-mentofhazardsofsubstances.

Article 1 of REACH

ANTARESisgoingonwiththeevaluationandassessmentoftheavailableNTM,inparticularQuantitative Structure-Activity Relationship

(QSAR) models,andthepromotionofnewtoolsandresources.

Promotion of Non-Testing Methods (NTM) for their use in the REACH context linking scientists, regulators and industries

to EVALUATEand VALIDATE

existing NTM fortheir application

according toREACH NEEDS

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http://www.antares-life.eu/reach-ntm.php

http://www.vega-qsar.eu

http://www.antares-life.eu/action1.php

REACH and NON-TESTING METHODS

QSAR tools for REACH purposes can be used for SEVEN REASONS

Innovative toolsTime for experimentsOccurrence of enough laboratories/resourcesReduction of costsUse of animalsPrioritization needsPro-active approach for greener chemicals

ForeachofthemwecanidentifytheCURRENTCRITICALISSUESandproposeSOLUTIONSthroughANTARES

3. OCCURRENCE OF ENOUGH LABORATORIES/RESOURCES

AshighlightedintheANTARESAction1,inEuropethereisalackoflaboratoriescapabletoperformtestsrequestedbyREACH.

ANTARES promotes new resources, collaboration and networking. With Italian Authorities for REACH a NETWORK OF LABORATORIES experton QSARs has been identified.

1. INNOVATIVE TOOLSCurrentmethodsarenotsufficient.InnovationisclearlymentionedwithintheREACHlegislation.ANTARES promotes a new platform wrapping several models: VEGA - Virtual models for property Evaluation of chemicals within a Global Architecture

2. TIME FOR EXPERIMENTS

Thetimerequestedtoproducewithin vivomethodsallthedatarequiredbyREACHwouldbeverylong.Industryfaceslongtimetogettheexperimentalvalues.

ANTARES promotes faster tools, e.g. through the VEGA platform.

4. REDUCTION OF COSTSCostsforexperimentswouldbebillionsofeurosandahugeproblemforSMEs.Partofthemcouldbeavoidedusingcheaperin silico methods.ANTARES promotes cheap and /or free solutions.

5. USE OF ANIMALSTheusageofanimalsisastrongethicalissueinEurope.REACHrequiresusingmillionsofanimals:partofthemcouldbeavoidedthroughin silicomethods.ANTARES promotes non-animal testing.

6. PRIORITIZATION NEEDSREACHrequiresprioritizingchemicals.Todayautorithiesarecapabletocheck5%ofchemicals.In silicomethodsoffertoolstosortthemaccordingtotheirtoxicity.

ANTARES promotes tools suitable for prioritisation (VEGA), and Italian regulators are interested in these tools.

7. PRO-ACTIVE APPROACH FOR GREENER CHEMICALS

Sofarchemicalshavebeenpreparedandtoxicityhasbeendiscoveredlater.Saferand“greener”productsneedtobedesignedsincethebeginning.ANTARES supports tools for safer chemicals, in contact with selected industries.

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http://www.antares-life.eu/index.phphttp://www.antares-life.eu/actions.phphttp://www.antares-life.eu/results.php

WEB PORTAL OVERVIEW

ANTARESWEBPORTAL OVERVIEW

The ANTARES project deals with innovative technologies and advanced interactive tools.

This implies an active and propositive presence in the Internet, with an updated and easy-to-use web site.

www.antares-life.euTheANTARESWebPortal isaimedtoprovidetheuserwitha prompt information about the project activities and the development itself of the project,justfromtheHome page throughavisualcodewhichgivesanimmediate overview of the state-of-the-art of the Actions.

Thestatusandresultsofeachactionareregu-larly updated, with public related documents uploaded to the website as downloadableresourceand/orasspecificwebsitesections.

LatestNews abouttheproject’sresults,aswellas about in silico approaches related news,eventsandresourcesarefrequentlypublishedandhighlighted.

ONGOINGAction

ACCOMPLISHEDAction

NOTSTARTEDAction

7WEB PORTAL SECTIONS

The contents of the ANTARES Web Portal are organized in the following main sections:

EVENTS RESOURCES SOFTWARE E-LEARNING

The SECTIONS of the WEBPORTAL

TheEVENTSsectionincludesalltheeventsrelated to the activities of the ANTARESproject, organized in the following sub-categories:

• Seminars for the European regulatory bodies

• International events’ participation

• Didactic courses and initiatives

• Events towards industry

• Workshops and seminars

• Meetings with national regulatory bodies

• Project meetings

EVENTS http://www.antares-life.eu/events.php

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http://www.antares-life.eu/action4.php

WEB PORTAL SECTIONS

RESOURCES http://www.antares-life.eu/resources.php

Allthepublic available documentsareupload-edintheRESOURCESsection.The resources have been organized in threesub-categories:

• OFFICIAL DOCUMENTS(deliverables,brochures,newsletters,boards,etc.)

• PRESENTATIONS givenbyANTARESbeneficiarieswithacknowledgementtotheproject

• POSTERS aboutANTARES

SOFTWARE http://www.antares-life.eu/software.php

TheSOFTWAREsectionhasbeenimplement-edonthebasisoftheactivitieswithinAction4 (List of (Q)SAR models for the ecotoxicologi-cal, toxicological and environmental endpoints for REACH, and their review)andincludesalistof available resources (free and commercialsoftware as well as articles regarding QSARmodels)possiblyusableformostlyallREACHendpoints.

This page allows the visualizing of the soft-wareavailable,aswellasthetypeofsoftware(both commercial and free or only free soft-ware)foreachendpoint.

The SECTIONS of the WEBPORTAL

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QSAR

WEB PORTAL SECTIONS

TheE-LEARNINGsectionprovidesdidacticma-terial forunderstandingQSARand is suitableforbeginnersandstudentsallowingtodown-loadorviewon-linepresentations,e-bookandothertypeoflearningmaterials.

Contentsareorganizedinsixareas:

E-LEARNING http://www.antares-life.eu/learning.php

In the Updates page you can find the last articles posted on the blog.In the sidebar there are a lot of useful links organized by categories.

Remember that to post comments you have to be registered to the site.

The Introduction section provides you general information about QSAR.This section answers questions about what QSARs are, why using QSARmodels and the relationship between QSAR and REACH European legislation.

In the Online Resources section you can find material like source code,software and other interesting links. Here practical aspects about QSAR

models are described. Furthermore from here it is possible todownload software and related tutorial to make your own predictions.

Finally in the F.A.Q. (Frequently Asked Questions) page you caninteract with our staff. Your impressions about the site and the QSARin general are very precious for us.

The Theory page studies deeply mathematical and statistical aspectsabout QSAR. Here you can find algorithms and equations

that describe how QSAR models work under the hood.

In the How to Use section there are useful video-presentation aboutpratical use of the software in order to obtain chemical prediction.

The SECTIONS of the WEBPORTAL

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1

2 3

4

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BENEFICIARIES

Project BENEFICIARIES

TheMARIONEGRIINSTITUTEFORPHARMACOLOGICALRESEARCH(IRFMN)isanot-for-profitbiomedical researchorganization, founded inMilan in1961,withresearchunitsalso in Bergamo, at Ranica – near Bergamo – and at Santa Maria Imbaro, near Chieti.TheInstitute’smainaimistohelpdefendhumanhealthandlife.TheLaboratory of Environmental Chemistry and ToxicologyatIRFMNiscoordinating/coor-

dinatedinthepast13ECprojects,andisparticipating,orhasparticipated,to17otherECprojects.These projects deal with QSAR, toxicity, InformationTechnologies, dissemination of knowledge and re-sultsand integrationofknowledge.Withinoneof theseprojects,CAESAR,asoftwareplatformhasbeendevelopedincludingavailableQSARmodelsforREACH.WithintheprojectDEMETRA,anewsoftwareforregulatorypurposesforpesticideshasbeendeveloped.

The ISTITUTO SUPERIORE DI SANITÀ  (ISS), es-tablishedinRome, isthe leadingtechnicalandscientific public body of the Italian NationalHealthService.Its activities include research, control, training

andconsultationintheinterestofpublichealthprotection.TheInstitute conducts scientific research in a wide variety of fields,fromcutting-edgemolecularandgeneticresearchtopopulation-based studies of risk factors for disease and disability. ResearchprioritiesarebasedonthosesetforthintheNationalHealthPlan.

FEDERCHIMICA  is the abbreviatednameoftheITALIANFEDERATIONOFTHECHEMICALINDUSTRY,foundedin1920.Atthepresenttime1,300com-panies,withatotalof94,000employ-ees,arepartofFederchimica.Theyaregrouped into 16 Associations, whichinturnaresubdividedinto43productgroups.Federchimica isamemberofConfindustria (General ConfederationoftheItalianIndustry)andCEFIC(Eu-ropeanChemicalIndustryCouncil).Itsprimary objectives are the coordina-tionandtheprotectionoftheroleofthe Italian chemical industry as wellas the promotion of its developmentcapacity.

The POLITECNICO DI MILANOUniversity was established in 1863andit isnowrankedasoneofthemostoutstandingEuropeanuniver-

sitiesinEngineering,ArchitectureandIndustrialDesign.TheDepartment of Electronics and Information of thePolitecnicodiMilanoisauniqueenvironmentthatblendscompetencesanddisciplinesusuallymapped inseparateCSandEEdepartments.AtDEIcross-fertilizationisaworkingrealitywhereresearchersareeagertotacklecomplexandchallengingproblems,contributingto shape key achievements in computer engineering, telecom-munications,systemsandcontrol,electronics. 

The KNOWLEDGEMINER SOFTWARE  isaGermanprivatelyheldcompanyinthefield of research, consulting, develop-

ment,andapplicationofuniqueself-organising,inductive,knowledgediscoverytech-nologies.ThecompanydevelopedtheKnowledgeMiner®softwarepackage,adistin-guishedcommercialself-organisingmodellingtool.Itimplementsaninnovativesetofhigh-performanceparallelalgorithmsformodellingandvalidationofcomplexsystemstoallowknowledgeextractionfromnoisydatainamostobjectiveandautomatedway.

IstItuto dI RIceRche FaRmacologIche maRIo NegRI (Coordinator)

IstItuto supeRIoRe dI saNItà FedeRchImIca

polItecNIco dI mIlaNo

KNowledgemINeR

Alternative Non-Testingmethods Assessed forREACH Substances

www.antares-life.eu

info@antares-life.eu

Alternative Non-Testingmethods Assessed forREACH Substances

LIFE08ENV/IT/00435

http://ec.europa.eu/environment/life/about/index.htm

LIFE (L’InstrumentFinancierpourl’Environnement)isthe EU’s funding instrument for the environment,launchedbytheEuropeanCommissionandcoordinatedbytheEnvironmentDirectorate-General.ThegeneralobjectiveofLIFEistocontributetotheimplementation,updatinganddevelopmentofEUenvironmentalpolicyandlegislationbyco-financingpilotordemonstrationprojectswithEuropeanaddedvalue.

LIFEbeganin1992andtodatetherehavebeenthreecompletephasesoftheprogramme(LIFEI:1992-1995,LIFEII:1996-1999andLIFEIII:2000-2006).Duringthisperiod,LIFEhasco-financedsome3104projectsacrosstheEU,contributingapproximately€2.2billiontotheprotectionoftheenvironment.

Thecurrentphaseoftheprogramme,LIFE+,runsfrom2007-2013andhasabudg-etof€2.143billion.ThelegalbasisforLIFE+istheRegulation(EC)No614/2007.

LIFE+ covers both the operational expenditure of DG Environment and the co-financing ofprojects.AccordingtoArticle6oftheLIFE+Regulation,atleast78percentoftheLIFE+budget-aryresourcesmustbeusedforprojectactiongrants(i.e.LIFE+projects).Duringtheperiod2007-2013,theEuropeanCommissionwill launchonecall forLIFE+projectproposalsperyear.

TheANTARES project has been declared eligible under the programme componentLIFE+ Environment Policy and Governance.

The Environment Policy & Governance component continues and extends the former LIFEEnvironment programme. It will co-finance innovative or pilot projects that contribute to theimplementationofEuropeanenvironmentalpolicyand thedevelopmentof innovativepolicyideas,technologies,methodsandinstruments.Itwillalsohelpmonitorpressures(includingthelong-termmonitoringofforestsandenvironmentalinteractions)onourenvironment.

The LIFE Programme

LIFE+