joint research centreEUROPEAN COMMISSION

2 0 0 0

ANNUAL REPORTInstitute for Health and Consumer Protection

Report EUR 19909 EN

EUROPEAN COMMISSIONJOINT RESEARCH CENTRE

The mission of the IHCP is to support EU policies for health and consumer protection. The Institute carries out researchto improve the understanding of the hazards, exposure and risks posed by food contaminants, drugs, chemicals, products,services and systems and to develop, validate and apply advanced methods and strategies of high scientific quality.

Mission

European CommissionJoint Research Centre (DG JRC)Institute for Health, and Consumer Protection (IHCP)

Editors:G.P. TartagliaA. Cardinali

Graphic design and layout:R. Sánchez • Information and Public Relations Unit • JRC Ispra

Legal NoticeNeither the European Commission nor any personacting on behalf of the Commission is responsible for the usethat might be made of the information contained in this publication.

EUR Report 19909 EN

Luxembourg: Office for Official Publicationsof the European Communities, 2001

ISBN 92-894-1332-8

© European Communities, 2001

Printed in Italy

Institute for Healthand Consumer Protection

Annual Report 2000Institute for Health and Consumer Protection

Foreword 4

Organisational chart 5

Executive summary 6

Scientific Highlights 7

Management Highlights 10

The Food Products Unit (FPU) 14

The European Chemicals Bureau (ECB) 22

The European Center for the Validation of Alternative Methods (ECVAM) 28

The Biomedical Materials and Systems Unit (BMS) 34

The Support to Pharmaceutical Research Unit (SPR) 40

CONTENTS

It has been an honour and a challenge to take up myduties as first Director of the Institute for Health andConsumer Protection on 01/03/2000. Now, after oneyear, I am proud and happy to welcome the issue of itsreport for the year 2000. The year just passed has beena though one, dense of events but, more important, fullof success stories, as detailed in the report.

Rapid developments in life sciences, the Commission’slegislative programme and the New Policy on Chemicalshave strongly influenced and accelerated the focusingand prioritisation of the Institute activities. The areasless relevant to th Institute’s mission have been discon-tinued or transferred. Others like GMOS related research,have on the contrary expanded in response to the fastchanging requirements for scientific support to Commu-nity policy making.

The strengthening of the interactive dialogue with DGs,the enlargement of its networking base and establish-ment as a major training provider, have rendered theIHCP the reference point for issues related to food andto the chemicals policy in Europe.

The IHCP has been central to the development of theJRC competence pillar on “Food, Chemical Products andHealth”. Through the Institute, the JRC is co-ordinatingthe European Network of GMO laboratories, has achieveda prominent position in the European Food Authority,under establishment and is central to the implementa-tion of the White Paper on Chemicals in Europe, for allaspects ranging from pure regulatory ones to the develop-ment of alternative methods. Moreover, other activities(e.g. support to pharmaceutical regulation, biomedical)have been highly recognised by our partners.

All these achievements were made possible with highcommitment from all the staff, which I wholeheartedlythank for their performance, sense of responsibility andpersonal participation in the Institute’s life.

The future requires continuous engagement to consoli-date some areas and to keep our deliverables at thehighest standards. I am sure that with such premises ourimpact in the European area will continuously increaseand further progress can be reported a year from now.

Barry McSweeneyIHCP Director

Foreword

4

5

Organigramme

Validation ofBiomedical Testing

MethodsM. Balls

Food ProductsE. Anklam

BiocompatibleMaterials and

SystemsH.Stamm

PharmaceuticalRegulatoryActivities

F. Argentesi

Management SupportG.P. Tartaglia

Toxicology and Assessment of

Chemical SubstancesG. Vollmer

DirectorB. McSweeney

6

Executive Summary

The year 2000 was the second year of operation of theJRC’s newest Institute. The Institute’s first Director, BarryMc Sweeney, was appointed on 1 March 2000; prior to this,Herbert J. Allgeier, Director-General of the JRC, acted asDirector of the IHCP. The IHCP has continued to progressand undergo a natural evolution in its working areas. Theappointment of the Director accelerated the focusing andprioritization of IHCP activities. The prioritisation, mainlybased on customer demand, has lead to the transfer ofsome activities (i.e. on electronic commerce), to the dis-continuation of the project “COCO” on release from con-sumer products, to the streamlining of projects on medicaldevices and to the expansion of other activities (e.g. GMO).

Strategy

Strategic plans were based on elements such as theCommissions legislative programme, the New Policy onChemicals, the White Paper on Food Safety and rapiddevelopments in life sciences. Driven by principles suchas the reinforcement of the dialogue with DGs and otherCommission services and the European Parliament tobetter focus on customer demand, the enlargement of itsnetworking base and the establishment of the Instituteas a training reference point, the IHCP has internallybecome central to the development of the JRC compe-tence pillar on “Food, Chemical Products and Health”,in collaboration with other Institutes, i.e. IRMM andIPTS. Externally it has become the reference point forissues related to food and chemicals products.

Evolution

Due to growing consumer concern, there has been persist-ent demand for work related to food safety and quality,leading to an expansion of activities in this area in thecontext of the Commission White Paper on Food Safety andthe proposal for establishing a European Food Authority.IHCP is leading a working group during the planning phaseof the food authority in order to avoid duplication of ac-tivities between the authority and the JRC will be avoided.

The IHCP will strengthen its involvement in fields relatedto the authenticity and quality of organic foods. A detailedreview of BEVABS work will take place in 2001. With regardto food safety, the evolution of the safety of feeding stuff

will be followed. Monitoring will continue on polychlo-rinated biphenyls, phthalates and other plasticizers inchildcare articles. There will be openings in new fieldssuch as neutraceuticals and proteomics.

The GMO area received a tremendous boost in the year2000, under the impulse of the Commission legislativeprogramme. New staff are being taken on and the con-struction of new laboratories is under way. IHCP is in-creasing its activities in the area of certified referencematerials and is setting up a molecular register for theidentification of GMOs. Through IHCP, the JRC will co-ordinate the recently established international networkof GMO laboratories, reference example in the context ofthe European research Area.

The forthcoming White Paper on safety of chemicals in-cludes the IHCP as one of the main participants takingpart in the formulation and further implementation ofthe chemicals policy. IHCP can be expected to providefurther impetus to the future development of the activ-ities of both ECVAM (European Centre for the Validationof Alternative Methods) and ECB (European ChemicalsBureau), which continue in their work related to thesafety of chemicals and chemical products.

The IHCP also continued its work on telematics, in relationto regulation of pharmaceuticals. Present support givento the European Medicine Evaluation Agency (EMEA) isbeing strengthened, in addition to the activity on thedevelopment of the Medicine Information Network forEurope (MINE). Biomedical research activities have beenre-oriented and concentrated on the reliability of medicaldevices, including implants, and progressive interdisci-plinary work is now being carried out on replacementhips, knees and cardiac stents. Current strategy and futureevolution in this area are based on the requirements ofan ageing European population and consumer demandfor better medical devices and early diagnostic systems.

A key activity has been the impulse given to the develop-ment of networking. Beside the GMOs network mentionedabove, a major network on food safety has been established.Moreover, the number of collaborations in the field of al-ternative methods has continued to increase, as well as thenumber of bi-lateral collaborations in all Institute’s areas.

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Food Products Unit (FPU)

Safety and Quality of Food

The analysis of food products and consumer goods isgeared to responding adequately and independently toconsumer concerns regarding food safety and quality,and providing high-level technical support for the im-plementation of EU policies in the field of food and re-lated items.

Evaluation of methods for the assessment of heat treat-ment of animal meat and bone meal: The IHCP is coordi-nating the validation study for a method based on animmuno-assay developed in the UK for the detection ofheat-stable proteins from ruminants and porcine incompound animal feed.

Central nervous tissue (CNT) in meat products: a newactivity started in 2000 for the determination of CNT(such as brain and spinal cord) in meat products, asspecified risk material (SRM). These investigations re-spond to the need to assess the risk of human exposureto transmissible spongiform encephalopathies (TSE).

Polychlorinated biphenyls (PCBs): two methods for therapid analysis of PCBs have been in-house validated andare accepted for use in routine analysis: the gas chro-matography/mass spectrometry (GC/MS) method basedon a simplified clean up procedure and an immuno-assay method.

European Office for Wine, Alcohol and Spirit Drinks(BEVABS): data on the 1999 vintage have been measured(nuclear magnetic resonance). Development of the data-base on authentic European wines continued and thesoftware was updated. Moreover, work on the develop-ment and validation for carbon-13 measurements is pro-gressing.

Vegetable fats: A method for the detection of cocoabutter equivalents (CBEs) in cocoa butter (CB) has beendeveloped.

Natural toxicants: A simple, environmentally friendlymethod based on thin layer chromatography (TLC) forthe quantification of aflatoxins in food and animal feedwas developed and validated. In the frame of support toCEN TC 275/WG 5, a suitable analytical method for thedetermination of aflatoxin B1 in baby food was deliveredat the meeting held in Rotterdam in February 2000.

Food Contact Materials: A study on the effects of thecomposition of can coatings on migration of ether degra-dation products (BADGE, BFDGE) was completed, as partof monitoring contaminants from food packaging (i.e.can coatings, baby bottles, baby food jars sealant etc.).Comparison of methods for the migration of Bisphenol Ain baby bottles was also completed. Validation of twomethodologies to test the migration of certain plasti-cizers from toys and childcare articles was carried out.

Scientific Highlights

8

GMOs

The GMO project addresses challenges related to bio-technology regulatory actions for environmental devel-opment, consumer protection and technological/indus-trial development, provides assistance to the Commission,to the relevant competent authorities and to Europeanand national expert Committees in their work on the im-plementation of the Biotechnology Directives. Throughthe IHCP, the JRC is co-ordinating the recently estab-lished international network of GMO laboratories.

A notification system called SNIF has been developedas specific scientific and technical support offered toDG Environment with respect to the implementation ofDirective 90/219/EEC on the contained use of geneticallymodified micro-organisms and Directive 90/220/EEC onthe deliberate release into the environment of GMO, in-cluding all amendments and technical adaptations.

Reference materials containing GMOs (produced by IRMM)have been extensively analysed by direct PCR and bynested PCR, with the application of a large variety ofPCR primers. This enabled new production protocols tobe developed and collaboration to begin on the produc-tion of new types of materials. Three training courseswere organized in collaboration with the World HealthOrganization. Applications for an additional ten coursesare being processed.

European Chemicals Bureau (ECB)

The European Chemicals Bureau provides scientific andtechnical support in the conception, development, imple-mentation and monitoring of EU policies on dangerouschemicals. It represents the focal point for collectinginformation on new and existing chemicals and the assess-ment of risks to workers, consumers and the environment.

ECB has introduced 11 new and revised testing methodsinto Annex V of Directive 67/548/EEC. The IUCLID data-base, already adopted in 1999 by the InternationalCouncil of Chemicals Associations (ICCA), has becomethe reference database for the world chemical industryfor the collection and distribution of chemical data, andhas now been enlarged to contains the revised sectionon Biocides. The second IUCLID CD-ROM was released inAugust 2000. In its present form, it contains data on2604 high production volume chemicals, including allavailable data on the toxicological and eco-toxicologicaleffects of these substances, together with summaries ofrisk assessment reports, where available, and other back-ground information.

European Centre for the Validation of AlternativeMethods (ECVAM)

The European Centre for the Validation of AlternativeMethods (ECVAM) is the international reference centrefor the development, and scientific and regulatory ac-ceptance of alternative testing methods, e.g. in vitrostudies using cell tissue cultures, computer based test-ing and the use of non-invasive technologies in humanvolunteers. This work aims at replacing, reducing or re-fining the use of laboratory animals and is applicable inmany different fields of the biomedical sciences.

Three scientifically validated in vitro methods (two forskin corrosivity and one for phototoxic potential) wereaccepted by EU Member States as Annex V test guide-lines in relation to Directive 67/548/EEC. The ECVAMScientific Advisory Committee endorsed the local lymphnode assay for skin sensitisation and the EpiDerm skincorrosivity test as validated methods, and an ECVAMformal validation showed that three in vitro tests forembryotoxicity had met the validation criteria for thestudy.

In vitro assays for haematoxicity are successfully beingapplied to pesticides, with both human and animalcells. Standard operating procedures for the use of hu-man spinal cord blood cells in clonogenic assays havebeen produced. An important contribution to the deri-vation of structure-activity relationships for predictingthe corneal permeability of chemicals and pharmaceuti-cals has been published.

9

Support to Pharmaceutical Regulation (SPR)

The SPR Unit provides management information/com-munication systems for the pharmaceuticals regulatoryprocess. These tasks largely consist in the safety valida-tion of medicinal products such as pharmaceuticals,vaccines, blood derivatives, radiopharmaceuticals andhomeopathic medicines, as well as biotechnological de-rivatives, to ensure that citizens’ health is protected.

Support to EMEA is being strengthened, in order to de-velop the Unified Tracking System (UTS) by integratingcurrently distinct marketing authorization procedureswith up to date telematic solutions: EudraTrack Mutualrecognition (EMR) and Application Tracking System (ATS).UTS is a telematic system for tracking all marketing sub-missions of medicinal products in Europe and it is capa-ble of detecting improper submissions.

Additional activities in this area include the design andimplementation of a centralized database service (namedMINE), which gathers all scientific, efficacy and safetyinformation on medicinal products which are authorizedwithin the EU.

The EudraNet network (EudraNET II) is being upgraded,by adding the modules VPN (Virtual Private Network),including PKI (Public Key Infrastructure), and aims toincrease the use of the currently used EudraNet I dedi-cated network services.

Biomedical Materials And Systems (BMS)

The work programme REMED (Reliability of medical de-vices) focuses on (a) the development, improvement andcharacterization of biocompatible and bioactive surfaces(in terms of tissue compatibility and duration), in par-ticular to improve haemocompatibility of cardiovasculargrafts, stents, cathethers, and the osteointegration of hipand knee replacement prostheses; (b) on release fromimplant materials (orthopaedic and dental implants);and (c) on performance testing of biomedical devices, insupport of harmonization of test methodologies on releasefrom and performance of medical devices, under clinicallyrelevant conditions, using a combination of advancedtechniques, and in support of Directive 93/42/EEC.

A 2-axis dynamic loading station for a hip joint simula-tor was designed and constructed. Tests have started onprogrammes which can be performed with up to threemillion simulated walking cycles.

Pre-normative research in support of the Nickel Direc-tive 94/27 was carried out, with the definition and pub-lication of selected test methods (EN 12472) beingadopted by the European Committee for the Standardi-zation (CEN).

The work programme MIMES (Minimally Invasive Medi-cal Systems) deals with medical imaging and therapy.While the diagnostic part related to PET was reduced in2000, the section involved in the development of opti-cal imaging techniques for minimally invasive diagnos-tics and therapy was enlarged.

A Fluorodeoxyglucose (FDG) production facility has beeninstalled on the Cyclotron premises. The module, com-plete with target, synthesis module and quality controlunit can deliver about 40 GBq at the end of each run.Clean rooms (class C and B) are also available for handlingthe tracers and to comply with GMP guidelines relatedto radiopharmaceutical production. Discussions have al-ready started with some companies concerning the pro-duction of radiotracers (renting of the facilities) torelease JRC staff from routine production.

The European Network for Optical Methods of MedicalDiagnosis and Monitoring of Diseases (MEDPHOT) waslaunched within the framework of a thematic networkexercise, with the BMS Unit acting as network manager.

10

Management Highlights

This chapter presents a review of achievements in hori-zontal/coordination activities,which range from defin-ing strategic directions and workprogrammes, to projectand total quality management, communication andmarketing, training, information technology and sup-port activities (safety, infrastructure, financial and per-sonnel administration).

Total Quality Management

The IHCP committed itself to TQM in November 1999. ATotal Quality Manager was appointed and took up hisduties on March 16, 2000. A “self-assessment” exercisetook place in 2000. 3 improvement teams were formedto handle the areas described below.

Communication

To improve dissemination of information within the In-stitute, an Institute intranet web site has been created(http://ihcp-agora’.jrc.it) and is operational since July2000. It was conceived as a repository of informationon internal procedures, guidelines, information concern-ing the daily life of the Institute and utilisation of re-sources, e.g. staff situation, arrivals/departures etc. Itincorporates the Units’ periodically issued newslettersand it also contains the possibility to exchange ideasand a space - the Director’s corner - where staff have adirect line with the Institute’s Director.

Project Management and Processes

A system to facilitate project reporting is being devel-oped. It will consist of a repository for project informa-tion and common reporting formats. Various adminis-trative processes were reviewed and new schemesimplemented. Attention is being focused on planningprocesses and internal document flow.

• Customer survey

As an integral part of TQM, a customer survey was heldamong the IHCP’s main institutional customers. The re-sults showed that the IHCP is highly rated for its scien-tific/technical work, expertise, quality of its results andcapability for fast response to emergency situations orextraordinary requests.

• Team Building Day

In response to the findings of the “self-assessmentexercise”, which requested improved corporate identity;a special team-building day was organized on 27 Sep-tember 2000. The event was attended by almost all staffand was very successful.

• Job descriptions

In the frame of the general European Commission ad-ministrative reform, a complete revision of job descrip-tions (tasks, duties etc.) took place in July 2000.

Prizes and Awards

The work performed on mycotoxins resulted in the awardof a prize. Two proposals were selected in the JRC inno-vation competition project: the first one on the refine-ment and commercialisation of a genetically engineeredneuronal model for toxicity testing and the second oneon a novel plasma reactor to treat the inner surface ofnarrow tubes (e.g. catheters). A prize was awarded forthe best paper published in ATLA (Alternatives to Labo-ratory Animals) to the group working on reprotoxicityand cardiotoxicity, who participated in the successfulvalidation of the embryonic stem cell test.

Financial Indicators

Significant changes have characterized budget evolu-tion in the year 2000 with the revision of the workpro-grammes, which reflect on the organizational structureand resource utilization.

Extra funds have been received for the GMO area; theLEPEC activity on electronic commerce has been ceasedand transferred to the Institute for Systems, Informat-ics and Safety (ISIS), allocating the related human re-sources to work on pharmaceutical regulation support.In the biomedical area, two workprogrammes have beendiscontinued (COCO: on release of consumer productswhere there is neither demand, nor a clear customer;and FUNSYS: on functional systems, which has been in-tegrated into REMED) and funds have been re-allocatedin the two remaining areas, to strengthen the emphasison the demands of an ageing population and the needfor better medical tools.

Competitive activities were undertaken in addition tothe institutional budget. This has allowed, the enlarge-ment of the IHCP network base. Far to be a pure eco-nomic incentive, these actions can be considered as areal indicator of the quality of the work performed andenable the Institute to increase its expertise and compe-tencies.

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Competitive actions (€)

SCA 1105000TPW 672000OTHERS 1076000

PROJECT Staff cost Credits TOTAL

Control of Quality & Safetyof Food & Related Items 4391 1725 6116

Support to the implementationof Community Policyon biotechnology (GMO) 1116 750 1866

5507 2475 7982

Validation of alternativesmethods (ECVAM) 3849 2347 6196

Chemical Products,environmental riskassessment (ECB) 5145 1054 6199

Telematic system for the EUpharmaceutical regulatoryactivity (ETOMEP) 2377 590 2967

LEPEC, Consumer ProtectionLab. Valid. Monitor.For Electronic Payment 861 160 1021

1232 4151 16383

Reliability of BiomedicalDevices (REMED) 4055 329 4384

Contam. of Nutrition &Consumer Prod due toMaterial Rel. (”COCO”) 2097 425 2522

MITRA, Medical Imaging andTherapy using Radio-tracers 804 90 894

Functional systemsfor Health andConsumer Protection 1371 48 1419

8327 892 9219

TOTALS 26066 7518 33584

* Work programme revised or stopped during 2000

FOOD

CHEMICALS

BIOMATERIALS

Institute IHCP 2000 - Execution by programme line (K €)(including competitive activities)

*

*

*

Personnel

Due to the revision of the workprogrammes and theboost in some areas such as GMO, there has been an in-crease in the nominal staff table, up to a total of 167staff members. The IHCP can count on significant ex-pertise in a wide range of disciplines, such as AnalyticalChemistry, Biology, Biometrics, Biophysics, Engineer-ing, Food chemistry, Information technology, Science,Medicine, Pharmacology, Physics, Radiochemistry andToxicology. The actual average staff number was 140 in2000, with positions vacant due to retirements and de-parture of short-term personnel. Suitable replacementsneed to be found in key specialized areas such as toxi-cology, molecular biology etc. A large contribution toInstitute activities is made by temporary staff (auxilia-ries, national experts, visiting scientists etc.) as well asPhD and Post Doc grant holders, for whom an extensiverecruitment campaign has been carried out.

Training

Training activities are being concentrated on the transferof key competencies to scientists from “candidate” coun-tries for EU membership and developing countries, withemphasis on training of young researchers. Several exam-ples can be given: training offered to the World HealthOrganization (WHO), sessions organized for the use of theIUCLID database on chemicals and additional trainingcourses related to detection methods for GMO/food safetyissues. It is also worth mentioning some single trainingactions whereby Stagiaires and Ph.D. students are hostedeither to complete their studies or to develop expertise ina subject. The intention is to intensify these activities:publicity has been made in specialized magazines and onspecific web sites (e.g. Marie Curie fellowships). In-housestaff training has also been emphasized: examples in-clude safety and specific technical subjects.

Informatics

In the context of the Communications ImprovementTeam work, a pilot project was initiated which will serveas a showcase of modern IT-based communication tech-nologies. The features of Windows 2000 and Exchange2000 (with standard Commission products) will providea standard working environment for all IHCP users.

Safety

Safety is a matter of great concern at IHCP, given therequirements of Italian Law nr. 626/94, the peculiarityof certain installations (e.g. Cyclotron), laboratories ofthe Institute, and QA/QC prescriptions. Over and abovesuch requirements, it is considered an integral part ofInstitute management to guarantee staff healthy work-ing places in which work can be carried out safely andin the best conditions.

The work on safety, prevention and protection has beenembodied in the “Safety project 2000” plan, elaboratedon the basis of the safety analysis carried out in 1999to fully comply with law 626/94.

Emergency and evacuation plans have been issued. Firerisk evaluation has taken place and been reported (in-cluding all electric and electronic appliances) and anintervention plan has been issued. Periodical checksand inspections are performed, without prior notice,following a hazard checklist. The ergonomics of workingplaces have also been studied.

An intensive training campaign on safety is taking place.In particular, 45 safety information courses for newcomerswere given in 2000 as well as two specific courses for thepersons responsible for safety in buildings. Courses forspecific teams working in the same environment havebeen formulated and just started (3 courses in 2000).

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Permanent staff average year 2000

Technicians 69Management & Support 17Scientific 54

Total staff average year 2000

Auxiliaries S/T 20Auxiliaries Supp. 9Grant Holders 22VS + END 7Trainees 17Permanent Staff 140

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Infrastructure

Beside the concentration of staff in a limited number ofbuildings, major work has been carried out to re-structurea building to host food loboratories and to re-structureanother one to host additional GMO laboratories.

External Communication

Press and media coverage

This year the IHCP received extensive press coverage:articles were published in well known newspapers suchas The Wall Street Journal, il Corriere della Sera, il Sole24 Ore, etc. Coverage was given in local newspapers anda special report on food safety and GMOs was publishedin the magazine Famiglia Cristiana. The BBC, RAI, andEuronews journalists visited the IHCP laboratories. Atele-training experiment was also carried out, for theRegione Lombardia authorities, presenting activities re-lated to coatings of biomedical implants (prosthetic de-vices).

Documentation

A brochure was published in 2000 to illustrate IHCP’sresearch activities. The brochure was distributed to thepress, the general public, to our partners and to politi-cal decision makers. Various information leaflets, flyers,project sheets, and posters were printed and distributedworldwide.

The Institute web site (http://ihcp.jrc.it) was createdand came into operation in January 2000. It provides adescription of the institute, its mission and objectives,an overview of activities, contact persons, a descriptionof work opportunities (for grantholders, visiting scien-tists etc.) and opportunities for collaboration and part-nership. It also contains links to specific project sites,containing detailed descriptions. The Institute web sitecan also be accessed through the JRC web site (http://www.jrc.cec.eu.int).

Events

General events worth reporting include contributions tothe exhibition at the European Parliament in February,participation in “Eurosalute” in Milan in October, organ-ization of various meetings on genetically modified or-ganisms and the chemicals policy. The JRC’s Open Day inMay saw a total of more than 1500 visitors to IHCP fa-cilities/laboratories. The visits of Commissioners PhilippeBusquin and David Byrne and the visit of EU PresidentRomano Prodi were very important for the IHCP. TheItalian President Carlo Azeglio Ciampi and the ItalianResearch Minister, O. Zecchino, also visited the IHCP.Visits to laboratories were organized for the President ofCNR, Lucio Bianco, the Finnish parliament’s Committeefor the Future, EP INDU members, the Industrial Union,and the JRC Alumni event. The IHCP had over 200 officialvisitors during the year.

FOOD PRODUCTS UNIT

In order to meet customer research and support needs,the FPU addresses two major areas: (1) activities withinthe field of food safety and quality and (2) issues on ge-netically modified organisms. During 2000, the FPU fo-cussed its many activities into three areas of food safety,namely a) support to research on transmissible spongi-forme encephalopathy (TSE) b) residues and contami-nants, and c) contact materials. Likewise, the projectson food quality have been concentrated into a) authen-ticity of wine and b) vegetable fats and chocolate.

Food and Feed Safety

Support to research on Transmissible SpongiformEncephalopathies (TSE)

Animal meal containing high-risk material is conceivedas the primary source of BSE. In order to inhibit a furtherspread of this disease, the European Commission im-posed a ban on the use of animal meal from mammals infeed for ruminants (Commission Decision 94/381/EC).The FPU provides scientific expertise for the establish-ment and enforcement of suitable regulations. Currently,there is only the microscopic technique (an official Euro-pean method) for tests to support enforcing the ban,though this approach has some major drawbacks. Thereis a need for other methods that are more suitable forroutine analysis and allow a high throughput of samples.

The FPU started searching for more appropriate methodsthat could be validated. A promising technique (devel-oped in the U.K.) based on enzyme linked immunosorbentassay (ELISA), was validated by the FPU. The methodproved to be suitable for this specific purpose and otherEuropean laboratories can successfully perform thismethod.

Future FPU activities in this field will focus on the useof other screening methods such as fourier transformnear infrared spectroscopy, differential scanning calori-metry and pyrolysis mass spectrometry, for proof ofanimal proteins in feed. In 2001 FPU will also be co-operating in an EU funded shared-cost action project,aimed at developing and validating methods for the de-tection of mammalian tissues in feed. FPU will also con-

tribute to setting up a sample bank and library of micro-scopic images on the Internet.

Safe rendering of animal by-products is an importantmeasure for preventing the spread of BSE. Since 1996rendering of animal waste must be performed at 133°C,3 bar for 20 minutes. Although rendering plants are re-quired to record temperature and pressure, it is hard tounderstand whether animal meal of unknown origin hasalready been treated according to this legislation. In1998 the FPU validated a method based on ELISA toprove whether appropriate sterilisation of animal mealhas taken place. This method works well but has thedrawback of requiring the animal waste to contain atleast 10 % pork. To circumvent this problem the FPU re-cently optimized an existing ELISA method for beef andevaluated this test kit by performing an in-house vali-dation study. Considering the positive results of thisstudy, the FPU is currently validating the method bycarrying out a collaborative trial.

Central nervous tissue (e.g. brain) in meat products

The emergence of a new variant of Creutzfeldt-Jakobdisease during the BSE epidemic led to the ban on theuse of specified risk materials (SRM) as a measure tominimize human exposure risk to BSE. The tissues of thecentral nervous system account for 95% of the infectiveload in a BSE-case approaching the end of the incuba-tion period. Central nervous tissues (CNT) such as brainand spinal cord are among the SRM whose removal atthe slaughtering stage must be ensured by permanentofficial control. The SRM must be incinerated to avoidtheir inclusion in the food chain.

The FPU has initiated a new activity in collaborationwith the University of Leipzig, dealing with the deter-mination of CNT in final meat products. This new field ofresearch responds to the need to assess human expo-sure risk to transmissible spongiform encephalopathies(TSE) via the food chain. The detection of CNT in the finalthoroughly homogenized and heat treated meat producthas recently been achieved by Professor Luecker of theUniversity of Leipzig.

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Food Products Unit

pf u Web Information resources

At IHCP site:http://ihcp.jrc.it/TheIHCP/Activities/ACTSafe.htmlhttp://ihcp.jrc.it/TheIHCP/Activities/ACTRele.htmlhttp://ihcp.jrc.it/TheIHCP/Activities/ACTGMOs.html

At the Food Products Unit Site:Food safety: http://food.jrc.it/activities/safety/index.htmFood quality: http://food.jrc.it/activities/quality/index.htmEuropean Wine Databases: http://food.jrc.it/activities/bevabs/index.htmContact Materials: http://food.jrc.it/activities/contact/index.htmGenetically Modified Organisms: http://food.jrc.it/activities/gmo/index.htmGMOs in Food and Environment: http://food.jrc.it/gmo/

17

The FPU is now organizing a collaborative study withthe participation of official control laboratories. The fi-nal validated method will help to establish an impor-tant measure of control throughout Europe, in additionto the existing or forthcoming prohibition of SRM andwill also help to control imports of final meat productsfrom third countries.

Residues and Contaminants

PCBs in food and feedingstuff

The reason for the high concentration of PCBs (poly-chlorinated biphenyls) discovered in pork and poultryduring the Belgian crisis, was found to be contaminatedfeedingstuff. In order to enforce the ban on feeding-stuff containing PCBs, (Commission decision 1999/788/EC), it was therefore of the utmost importance to ana-lyse a high number of feed and food samples. The FPUdeveloped and validated two analytical methods whichallow a great increase in the throughput of samples. TheFPU is currently organizing a ring trial on detection ofPCBs in feed with 27 laboratories from 14 MemberStates. A serious bottleneck in PCB analysis, in terms oftest duration, is the extraction step. The FPU has startedto employ more rapid techniques such as “pressurizedsolvent extraction” to analyse feed samples, followingconventional analytical methods (GC/MS). Consideringthe encouraging results of this study, the FPU will com-bine this extraction method with immunoassay techno-logy in our future research activities, in order to achievea further improvement of PCB analysis.

Mycotoxins

Research on mycotoxins in the FPU focussed on severalimportant fields in support to European legislation andissues of emerging interest for consumer protection. Apre-requisite for the monitoring of contamination liesin precise analytical methods. These highly toxic me-tabolites (aflatoxins) which can be found in food andfeed are regulated by Directive 1998/1525/EC, whilecontamination problems in imported food have alreadyled to European wide import bans (EU Decisions 1997/613/EC and 1999/356/EC).

The FPU has already developed and validated state-of-the-art analytical methods based on liquid chromato-graphy combined with an immunoaffinity clean-up step.In 2000 special effort was put into the development ofvery simple and precise methods, which can be used asmonitoring tools by developing countries to check com-pliance with EU legislation for export purposes. Themain reason for this activity is that developing countriesare producers of food which is susceptible to aflatoxincontamination (e.g. peanuts, pistachios, figs, corn andspice).

The FPU has produced a method based on the easy-to-use principle of thin-layer chromatography (TLC) whichis suitable for monitoring aflatoxins at European legis-lative limits. In addition, two novel and simplified de-vices for the quantification of aflatoxins were devel-oped. A patent has been filed for one of these noveldensitometers and a staff member of the FPU receivedthe “Bruno-Rossmann-Preis 2000” from the GermanChemical Society (Gesellschaft Deutscher Chemiker) forthis innovative approach. Another device based on amodified office scanner was produced in collaborationwith the Fraunhofer-Institute for Optics in Jena (Ger-many).

Underlying research has also been performed in the areaof improvement of derivatization techniques for thedetermination of aflatoxins in various food matrices. Adirect comparison between two derivatization systemsinvolving the bromination and UV irradiation techniqueswas performed, showing the suitability of both tech-niques. In addition, a multi-method for screening andquantification of several mycotoxins in one analysis runhas been developed.

18

Contact Materials

Natural and synthetic materials such as plastics, paperand board, metals and ceramics are commonly used tomanufacture consumer goods and for food packaging.The safety of such materials relies on ensuring thatthere is no migration of substances at unsafe levelsfrom the material to food or to humans during contact.The activity on contact materials targets consumergoods such as children toys and food packaging materials.

Food packaging

Safe and high quality food supplies rely on being effi-ciently protected from deterioration. Various food con-tact materials and ingredients can be used for foodpackaging as long as they do not pose health concernsto consumers, which may occur when some substancesmigrate from the food packaging into the food. Migra-tion is the only parameter that originates from thepackaging itself and may cause it to inadvertently affectthe food or pose health concerns to the consumer.

Migration of substances used in organic coatings andlacquers for food cans may raise concern for humanhealth. For example, in recent years Bisphenol A diglycidylether has been reported by several Member States inconcentrations higher than the permissible level statedin Directive 90/128/EEC. Recently, the FPU has performedextensive surveys on various canned market products.

Canned foods typically have an extremely long shelf life(up to 3 years) and high heat sterilisation treatment;therefore it is necessary to understand the effects oftemperature and storage on migration of BADGE. Aproject on kinetics of migration and degradation ofBADGE was completed after 1-year storage.

For a better understanding of the migration potential ofvarious coating substances, a joint industry project wascarried out on the effects of the composition of cancoatings on migration of BADGE, BFDGE, their degrada-tion products and substitutes. Migration levels were lowin all cases.

Contaminants in polycarbonate baby bottles can con-tain a residual proportion of Bisphenol A (BPA) due tomanufacturing and/or subsequent processing. Bisphe-nol A has been considered to be an endocrine disruptorand it is important to monitor the absence of migrationof such substances from articles and contact in food. Aworst-case methodology for migration measuring wasapplied to a European survey of baby bottle samplesfrom all EU Member States. The results showed that mi-gration remained below the specific migration limit laidout in Directive 90/128/EEC.

Refined soybean oil has been extensively used in theplastics industry in the form of epoxidised soybean oil(ESBO). ESBO is primarily used as a plasticiser and sta-biliser for polyvinyl chloride (PVC) and other plastic ma-terials. One common application of ESBO is in the PVClining of baby food glass jars. The FPU initiated aproject on the determination of ESBO used in the seal-ing ring for vacuum-packed baby food jars. An improvedmethodology was implemented for the analysis and amonitoring study is under progress on more than 250jars collected in all EU Member States.

A European Database of substances used in materialsand articles in contact with food has been made availa-ble to the public. These substances are being gatheredin a reference collection, characterized physico-chemi-cally and are available at the FPU. To facilitate access toEuropean Commission documents and provide a publicservice with relevant information, the FPU developedan Internet site dedicated to food contact materials(http://cpf.jrc.it/webpack). It contains legislative in-formation in downloadable format as well as informa-tion on contacts with authorities and organizations inthe field of food contact materials, and methods foroverall migration. A satellite site (http://cpf.jrc.it/smt)is dedicated to physicochemical and spectral informa-tion as well as analytical methods on an increasingnumber of regulated substances.

Toys and childcare articles

It is particularly important to assure the safety of theyoungest consumers: babies and infants. Since commonconsumer goods may be in prolonged contact with babies’mouths, a potential migration of substances throughmembrane contact would have a stronger effect on theirsmaller bodies. Phthalates are typically used as softenersin soft PVC toys and childcare articles. Renewed healthconcerns regarding these substances recently resultedin a temporary ban on the use of phthalates in toys(Commission Decision 1999/815/EEC). This has givenrise to the need not only for estimating the potentialexposure of infants to a variety of phthalates by mouth-ing such toys, but also developing the means to testthese toys or childcare articles with mechanical means.The FPU is currently co-ordinating the validation of 2methods at a global level. The FPU will extend the in-vestigation to the migration of other plasticisers.

19

Food Quality

Vegetable fats in chocolate

The new European Chocolate Directive 2000/36/EECnow allows the addition of up to 5 % of vegetable fats,the so-called cocoa butter equivalents (CBEs), otherthan cocoa butter (CB) in chocolate products. The fol-lowing permitted fats are specified in the directive:palm oil, illipé (Borneo tallow or tengkawang), sal,shea, kokum gurgi and mango kernel. In addition to themandatory labelling of the addition of vegetable fatsother than cocoa butter, labelling to indicate that thosefats have not been added is also allowed. Appropriatetesting methods are the pre-requisite for implementa-tion of the Directive. In order to facilitate the analysis,the FPU (in collaboration with the Institute for Refer-ence Materials and Measurements) is certifying a cocoabutter reference standard. A pre-certification study wascarried out in 2000 and the materials have been pre-pared. The certification exercise will be completed in2001. However, there is still a perceived need withinofficial control laboratories for rapid screening methodsfor the quantification of such vegetable fats in choco-late in order to implement the new directive and tohandle a large throughput of samples. The FPU hastherefore recently developed a simple and reliable ana-lytical approach, which will be validated in an interna-tional ring test in 2001. In addition, the FPU has inves-tigated appropriate methods to gain information aboutthe analytical threshold (in case of negative labelling).

Polyphenols - making chocolate a functional food?

Today it is widely accepted that a healthy diet or the in-take of certain dietary components can contribute toachieving optimal health and development. Reducingthe risk or delaying the development of cardiovasculardisease, cancer and other age-related diseases are alsoimportant factors. Recently, polyphenols have gainedattention as non-nutrient compounds of our diet (e.g., infruits, fruit juices, tea, red wine and chocolate), owingto their antioxidant capacity and their possible bene-ficial implications to human health. However, there isstill a need for suitable methodologies to quantifypolyphenols in food and to show their bioavailabilityfrom diet. Therefore, to obtain reliable data on polyphe-nol content in foods, a complete methodology based onmodern analytical techniques has been set up for theanalysis of chocolate polyphenols.

Authenticity of Wine

Since wine has always been subject to fraud, the Euro-pean Union has created strict regulations to protect theEuropean consumer from adulterated products. The Euro-pean office for wine, alcohol and spirit drinks (BEVABS)was established as part of the IHCP in 1993. Its aim is

to manage a database on authentic European wines(started in 1991) to combat major fraud in the winesector. BEVABS provides the basis to share experience atEuropean level with the aim of improving and harmo-nizing the control of wine products and strengtheningthe European network of control laboratories using iso-topic techniques. It co-ordinates the EU Wine Databankactivities as well as the need for training and transfer ofknow-how to new Member States Laboratories.

Wine Databank

Apart from the collection of isotopic data from the 1999vintage, a number of actions have been undertaken toimprove the control of wine. The development of thenew software “Db Wine” for the management of the EUwine data bank has been completed.

Improved analytical methods

Another important step forward in 2000 was the pro-posal of a method for measuring of the carbon-13 iso-topic content in wine ethanol. This is now on its wayto being adopted as an official method. Finalizing theofficial adoption of a number of methods for the analy-sis of spirit drinks for an EU regulation is the direct out-come of a shared cost action project (SPIRITS) in whichBEVABS was one of the main partners. The first 4 methods(alcohol grade, dry extract, density and congeners) wereincluded in the EU regulation EC 2870/2000 on spiritdrinks. Wines suspected of adulteration were taken fromthe European market for analysis at the request of the“Office de Lutte Anti Fraudes” (OLAF) anti-fraud inspec-tors.

20

Genetically Modified Organisms (GMOs)

There has been intense public and political debate onGMOs and how they relate to environmental, food andfeed safety. The moratorium for EU approval, introducedin June 1999, is still in place. In addition, MemberStates have called for Commission Decisions. The GMOdebate is also ongoing in non-EU countries.

GMOs in the environment

For a number of years the IHCP has been collectingcases from Member States, describing the summaries ofdeliberate field trials involving GMOs that are carriedout for research and development purposes. Software hadbeen developed that allows Member States to exchangedata with the JRC and a WWW site had been created(http://biotech.jrc.it/) where an up-to-date overviewcan be consulted.

GMOs in food

Assessing the compliance of food products with the Euro-pean Union GMO Regulations is based on detection,identification and quantification. The analytical methodsfor detection must be sensitive and reliable enough toobtain correct results in all control laboratories. Sincedetection becomes more difficult after processing, in2000 the FPU validated another screening method forthe detection of GMOs in highly processed food samplessuch as biscuits. Specific information has to be availablefor the identification of GMOs. In addition, detectioncannot take place without knowledge of the details ofthe molecular make-up of the GMOs. The FPU is in theprocess of setting up a molecular register, which, be-sides the scientific data, also contains the tools forcontrol authorities to design appropriate identificationmethods. In 2000 the FPU validated a method to quan-tify the amount of GMOs in raw materials. The results ofthe validation study have shown that in this specificcase about 70% of correct results are obtained for 1%GMO-containing raw material. Sound methods can onlybe developed if appropriate reference samples are avail-able for GMOs. The Institute for Reference Materials andMeasurements (IRMM) takes the lead in the productionof these samples. The FPU has collaborated intensively

with IRMM on the development of appropriate produc-tion protocols and on the characterization of the refer-ence samples produced.

“European Network of GMO Laboratories”

A “European Network of GMO Laboratories” was createdin 2000 and is being organized and coordinated by theJRC. 38 experts from national enforcement laboratoriesand 18 European Commission representatives from vari-ous services held a first meeting in June to discusstechnical issues for the implementation of EU biotech-nology regulations. The scope of this meeting was tounderstand the needs of the Member States’ referencelaboratories on GMO detection in order to have a tech-nical dialogue and to prioritize the most urgent ques-tions to be addressed. Discussions focussed purely onscientific matters and identified the need for the crea-tion of the following specific working groups to cover:

• Appropriate protocols for validation studies and forproficiency testing.

• Appropriate reference materials.

• The design, content and function of a molecular register.

• Compatibility between methods and the eventual re-quirements for further research to understand the ap-propriateness of DNA and protein based methodologies.

Training

The FPU and the World Health Organization (WHO)co-organized a series of laboratory training courses on“The Analysis of Food Samples for the Presence of Ge-netically Modified Organisms”. Four training courses(each lasting one-week) were carried out in the FPU’sGMO Laboratory in 2000. Participants came from memberstates, accession countries and from many other countriesthroughout the world. Training will continue in 2001.

21

Publications 2000

Gilbert J., Simoneau C., Cote D. and Boenke A., “An internet compendiumof analytical methods and spectroscopic information for monomers and ad-ditives used in food packaging plastics”, Food Add. Contam, 17, 889 (2000).

Lipp M., Anklam E. and Stave J.: “Validation of an immunoassay for the de-tection and quantification of Roundup-Ready soy beans in food and foodfractions”, J. AOAC Internat. 83, 919 (2000).

Simoneau C., Lipp M., Ulberth F. and Anklam E.: “Quantifica-tion of cocoabutter equivalents in mixtures with cocoa butter by chromatographic methodsand multivariate data evaluation”, Eur. Food Res. Technol., 211, 147 (2000).

Stroka J., Anklam E., Jörissen U. and Gilbert J.: “Immuno-affinity columnclean-up with liquid chromatography using post-column bromination for thedetermination of aflatoxins in peanut butter, pistachio paste, fig paste andpaprika powder: a collaborative study”, J. AOAC Internat., 83, 320 (2000).

Stroka J., Petz M. and Anklam E.: “Analytical methods for the determina-tion of aflatoxins in various food matrices at concentrations regarding thelimits set in European Regulations: Development, characteristics and limits”,Mycotoxin Res. 16, 23 (2000).

Theobald A., Simoneau C., Hannaert P., Roncari A., Rudolph T. and AnklamE.: “Occurrence of bisphenol-F-diglycidyl-Ether (BFDGE) in fish canned in oil”,Food Add. Contam, 17, 881 (2000).

Von Holst C., Honikel K.O., Unglaub W., Kramer G. and Anklam E.“Determination of an appropriate heat treatment of animal waste by using theELISA technique”, Meat Sci. 54, 1 (2000).

Wollgast J. and Anklam E.: “Polyphenols in chocolate: is there a contribu-tion to human health?”, Food Res. Internat 33, 449 (2000).

Shared Cost Actions and other competitive projects

During 2000, the FPU was partner in 10 shared cost action (SCA) projects.

In the course of 2000, 6 proposals for share cost actions were submitted.

Support to CEN (European Committee for Standardization)

In 2000 the Food Products Unit actively participated in thefollowing Technical Committees (TC) and Working Groups (WG):

• CEN/TC 275 (Food analysis – horizontal methods)• CEN/TC 275/WG 5 (Mycotoxins)• CEN/TC 275/WG 11 (Genetically modified organisms)• CEN/TC 194 (Materials and articles in contact with food) - four

working groups.

Contacts

Head of UnitElke AnklamTel.: +39 0332 785295Fax: +39 0332 785930elke.anklam@jrc.it

Food and Feed Safety ControlSupport to TSE researchJosefa Barrero-MorenoTel.: +39 0332 789863Fax: +39 0332 785930josefa.barrero-moreno@jrc.it

Residues and contaminantsChristoph von HolstSupport to TSE researchChristoph von HolstTel.: +39 0332 785288Fax: +39 0332 785930christoph.von-holst@jrc.it

Contact MaterialsCatherine SimoneauTel.: +39 0332 785889Fax: +39 0332 785930catherine.simoneau@jrc.it

Food Quality ControlVegetable fats and chocolateElke AnklamTel.: +39 0332 785295Fax: +39 0332 785930elke.anklam@jrc.it

Authenticity of wineClaude GuillouTel.: +39 0332 785889Fax: +39 0332 785930claude.guillou@jrc.it

GMO GroupGenetically modified organismsGuy van den EedeTel.: +39 0332 785239Fax: +39 0332 785930guy.van-den-eede@jrc.it

EUROPEAN CHEMICALS BUREAU

Chemical substances: Risk Assessment

The European Chemicals Bureau (ECB), provides scien-tific and technical support to the conception, develop-ment, implementation and monitoring of EU policies ondangerous chemicals. It represents the focal point forcollecting information on new and existing chemicalsand manages the assessment of risks (hazard and riskassessment) posed to workers, consumers and the envi-ronment. It supports legal classification and labelling,the notification of new substances, information exchangeon import and export of dangerous substances, the de-velopment and harmonisation of testing methods andthe authorization of biocides. Directives supported are67/548/EEC, 93/67/EEC, 96/56/EC, 97/56/EC, 98/8/ECand the regulations are 2455/92, 793/93, and 484/94.

A new chemicals policy is being established in the EU.IHCP, through ECB and ECVAM, takes a central role inthe establishment of this policy: further expansion ofactivities in this field is expected.

Existing chemicals

ECB is responsible for the scientific and technical sup-port to Council Regulation EEC 793/93, with regard tothe first three steps of the Regulation, i.e. data collec-tion, priority setting and risk assessment.

Data collection

All data have to be submitted in the Harmonised Elec-tronic Dataset (HEDSET) format and are managed by theInternational Uniform Chemical Database (IUCLID),both developed and maintained by ECB. IUCLID hasbeen adopted as the standard database by the Interna-tional Council of Chemical Associations (ICCA) and isnow de facto the reference database for the WorldChemical Industry to collect and distribute data onchemicals.

Priority setting

In consultation with Member States the Commission,must regularly draw up lists of priority substances, onthe basis of collected information, taking into account

their potential effects to man or the environment.Three priority lists have been published so far.

Risk assessment

Substances on the priority lists must undergo an indepth risk assessment (following the Regulation EC1488/94, implemented in the detailed Technical GuidanceDocuments (TGD) on Risk assessment for New and Exist-ing Substances), covering the risks posed to man and tothe environment. After adoption of the risk assessment,three publications are produced (comprehensive risk as-sessment report in 3 formats: book, IUCLID and ECB home-pages, summary in 2 formats: book and ECB homepagesand conclusions in the Official Journal).

Specifically in 2000:

Upgrade of the database IUCLID to include the Biocidessection. Release of the second IUCLID CD-ROM in August2000.

High production volume chemicals in IUCLID has raisedto 2604, including all available data on toxicologicaland eco-toxicological effects of these substances, to-gether with summaries of risks assessment reports, whereavailable, and other background information.

New substances

Activities regarding new substances are carried out tofulfil the technical and scientific obligations of the ECregarding the notification schemes and risk assessmentfor all new chemicals made available in the EU, as laiddown in the Directives 67/548/EEC and 96/67/EEC. In2000, 400 summary notification dossiers were distributed.

240.000 Euros were assigned to the JRC for the ECB-NETproject within the I.D.A. programme (Interchange of databetween Administrations, http://europa.eu.int/ISPO/ida/ida.html), which involves a large number of cus-tomer DGs (DG AGRI, ENTR, ENV, MARKT, FISH, SANCO,EMPL, TREND).

24

European Chemicals Bureau

ce bWeb Information resources

At IHCP site:http://ihcp.jrc.it/TheIHCP/Activities/ACTChem.html

At the European Chemicals Bureau site:Home Page: http://ecb.ei.jrc.it/Existing Chemicals: http://ecb.ei.jrc.it/existing-chemicals/New Substances: http://ecb.ei.jrc.it/new-chemicals/Biocides: http://ecb.ei.jrc.it/biocides/Classification and Labeling: http://ecb.ei.jrc.it/classification-labelling/Testing methods: http://ecb.ei.jrc.it/testing-methods/Import/Export: http://ecb.ei.jrc.it/import-export/

The ECB project aims to develop a network for electronicdata transmission between the ECB and competent au-thorities in the Member States. The project has been al-located funds for a preparative and a feasibility study.The work has been contracted out and will initiate earlyin 2001.

The ECB provides technical and scientific support forthe implementation of the Directives 67/548/EEC,93/67/EEC and 98/8/EC, and regulations 793/93 and2455/92 as well as several other legal provisions.

Testing Methods

The seven following methods are to be added to part Cof Annex V:

C.14. Fish, Juvenile Growth TestC.15. Fish, Short-Term Toxicity Test on Embryo and

Sac-Fry StagesC.16. Honeybees – Acute Oral Toxicity TestC.17. Honeybees – Acute Contact Toxicity TestC.18. Adsorption/desorption using a batch equilibrium

methodC.19. Estimation of the Adsorption Coefficient (KOC)

on Soil and on Sewage Sludge using High Per-formance Liquid Chromatography (HPLC)

C.20. Daphnia Magna Reproduction Test

Method B.1. Acute Toxicity (oral, the classical LD50 test)will be deleted from Annex V.

During 2000 activities centred on continuing the devel-opment of Testing Methods for MMMF. Activities consist-ed in the calibration of the test on Sub-chronic InhalationToxicity of Synthetic Mineral Fibres in Rats and continu-ing the discussions with partners for the further devel-opment of the tests:

• Biopersistence of fibres after short-term exposure byinhalation.

• Biopersistence of fibres after intratracheal instillation.

New Chemicals

Totally, over 5000 notifications, including over 3000substances, have been submitted since 1983, currentlyequivalent to about 400 notifications per annum. Irre-spective of notification date, during the year 2000 a totalof 900 dossiers (comprising 475 new notifications and425 updates) were distributed from ECB to MSs. In addi-tion, 227 final proposals for classification and labellingwere distributed. Updates replace original notificationsand therefore are not included in the notification statis-tics. These figures represent a further increase in notifi-cation submissions with respect to 1997, 1998, and 1999(See table below).

Annual notification statistics since 1983, analysed byMS, show that over half have been combined contribu-tions from the UK and Germany. With regard to the ori-gin of the substances, about half the new commercialchemicals marketed in the EU during the year 2000 wereforeign imports, principally from the USA.

Terrestrial Model Ecosystems (TME) (project ENV4-CT97-0470)

The project analyses possible uses of Terrestrial ModelEcosystem (TME) data for regulatory purposes, focusingon current approaches for Environmental Risk Assess-ment for industrial chemicals, Biocides and plant pro-tection products.

25

0

10

20

30

40

50

60

70

80

90

100

19 19 18 18

40 42

0 0 0 00 02 2

77 79

Phys-chem Human Health Environment Total

Methods in Annex V after 27th ATP (February 2000)

0

50

100

150

200

250

300

350

400

450

500

Notifications Updates Find C&L proposals

Number of notifications submitted annually to ECB(yearss 1997 to 2000)

1997199819992000

Existing TM in AnnexV, before 27th ATP

New TM in27th ATP

Revised TM in 27th

ATP

Resulting TM inAnnex V, after 27th

ATP

Existing Chemicals

Data distribution

The IUCLID CD-ROM “Year 2000 Edition”, containing thephase II data and the updates for phase I submissions,was released in August 2000. The product is distributedthrough the Publication Office in Luxembourg.

Risk assessment

During the first quarter of 2000, the 4th Priority List un-derwent both informal and formal Interservice Consul-tation and was finally adopted on 31 May 2000. This listcontains priority substances for risk assessment reports,which are prepared by member States.

Risk assessment reports finalised in 2000

Technical Guidance Documents

The ECB initiated the revision of the Technical GuidanceDocuments (TGD) in support of Commission Directive93/67/EEC on risk assessment for new notified substancesand the Commission Regulation (EC) 1488/94 on riskassessment for existing substances and on Directive98/8/EC concerning the placing of the biocidal productson the market. This work will last several years.

Classification and labelling

The 28th ATP was prepared and is waiting to be en-dorsed by the Member States at the TPC voting meetingin Brussels 25 January 2001. This ATP includes:

• Updated, corrected and recast version of Foreword toAnnex I (incl. Tables 1A and 1B),

• Revisions of Annex I entries of 132 Existing and 7New Notified Substances,

• New Annex I entries of 53 Existing, 283 New Notifiedand 14 New Active Pesticide Substances,

• Two deletions of Annex I entries (covered by otherAnnex I entries).

26

3,4-dichloroaniline 95-76-1 DE

Diphenyl ether, octabromo der. 32536-52-0 FR*/UK

Bis(pentabromophenyl)ether 1163-19-5 FR*/UK

Methyl acetate 79-20-9 DE

hydrogen peroxide 7722-84-1 FIN

Toluene 108-88-3 DK

di-”isononyl” phthalate 28553-12-0 FR

1,2-Benzenedicarboxylic acid,di-C8-10-branched alkyl esters, C9-rich 68515-48-0 FR

di-”isodecyl” phthalate 26761-40-0 FR

1,2-Benzenedicarboxylic acid,di-C9-11-branched alkyl esters, C10-rich 68515-49-1 FR

tert-butyl methyl ether 1634-04-4 FIN

*Human Health Only

0

100

200

300

400

Num

ber o

f Ann

ex I

Entri

es

28. ATPExisting Substances

28. ATPNew Substances

283

147

132

53

revisedadditionalrevisedadditionaladditionalnew pest

27

Export/Import

The ECB continues with the project in collaboration withUNITAR to develop a National Profile Homepage. This isan Internet site where all the information on nationalprofiles has been produced by many countries either incollaboration with UNITAR or independently. The idea ofsuch a profile is to create a national basis in order tounderstand the present state within the country andhow to proceed towards better chemical management inthe future. The site was made available to the public in2000 at the address:http://www.unitar.org/cwm/nationalprofiles/index.htm

The ECB finalized the Internet version of 20 nationalprofiles during 2000, adding up to a total of 35 profileson the web site. In addition, UNITAR and ECB are pre-paring a CD reflecting the web site for interested partieswho have no web access.

A new web version of the EDEXIM database has been de-veloped to assist the export notification system underthe voluntary agreement. The database will then sup-port the current Regulation contemporarily with thenew yearly notification system.

Biocides

As a follow-up to the Directive, the Council agreed onthe review regulation for existing active biocidal sub-stances proposed by the member states in September2000. The ECB prepared the technical issues around theimplementation of the review regulation.

The main issue solved was that on the waiving of datarequirements and an updated version of the guidancedocument was placed on the web in October 2000. Up-dated versions of two other guidance documents on An-nex I (approved active substances) entry and productevaluation were circulated to the member states for dis-cussion in January 2001. The revision of the risk assess-ment guidance document for new and existing chemi-cals and biocides was brought forward.

Exposure is a major issue for the Biocides and the ECBhosted an OECD workshop on environmental exposure towood preservatives. Furthermore, the ECB was the Com-mission’s representative in the Biocides environmentalexposure project. Similar projects were launched for thehuman exposure.

An integral part of the support to the review regulationis a well functioning data base support. In this context,a first version of IUCLID for Biocides was finalized.

Publications 2000

Rasmussen K. and MacLellan M. A.: “The control of active substances usedin biocides in the European Union by means of a review regulation.” Envi-ronmental Science and policy. In print (2001).

Rasmussen K.: “The biocides directive and the review regulation” BIOCIDESTODAY supplement to Chemistry Today (2001).

Payá Pérez A.B., Rahman M.S. and Larsen B.R. : “Mobility Assessment ofHydrophobic Pesticides in the Surfactant-Soil-Water System”. Pesticide/SoilInteractions: Some Current Research Methods. EC, INRA (France) <<Tech-niques et Practiques>> series, 490 pp.

Weyers A., Sokull-Klüttgen B., Baraibar-Fentanes J. and Vollmer G.: Acutetoxicity data: A comprehensive comparison of results of fish, Daphnia andalgae tests with new substances notified in the EU. Environ. Toxicol.Chem. 19, 1931-1933.

Weyers A. and Vollmer G.: Algal Growth Inhibition: Effect of the choice ofgrowth rate or biomass as endpoint on the classification and labelling ofnew substances notified in the EU. Chemosphere 41, 1007-1010.

D. Vialaton, D. Baglio, C. Richard, H. Skej¢-Andresen, and A.B. Payá Pérez.Phototransformation of Priority List Organic Chemicals and Pesticides inWater. (Fresenius Environ Bull, in print 2001).

Heidorn C., Caruso S., 2000. The “IUCLID CD-ROM, Year 2000 Edition”,Public data on high volume chemicals, EUR Report 19559 EN, Office forOfficial Publications of the European Communities, L-2985 Luxembourg,ISBN 92-828-8641-7.

Hansen B.G., Munn S.J., Schoening G., Luotamo M., van Haelst A., HeidornC.J.A., Pellegrini G., Allanou R. and Loonen H. Editors (2000). EuropeanUnion Risk Assessment Report: 2-(2-Methoxyethoxy)ethanol. Luxembourg:Office for Official Publications of the European Communities. 1st PriorityList, Volume 1. EUR 18999. ISBN 92-828-8399-X.

Hansen B.G., Munn S.J., Schoening G., Luotamo M., van Haelst A., HeidornC.J.A., Pellegrini G., Allanou R. and Loonen H. Editors (2000). EuropeanUnion Risk Assessment Report: 2-(2-Butoxyethoxy)ethanol. Luxembourg:Office for Official Publications of the European Communities. 1st PriorityList, Volume 2. EUR 18998. ISBN 92-828-8398-1.

Hansen B.G., Munn S.J., Schoening G., Luotamo M., van Haelst A., HeidornC.J.A., Pellegrini G., Allanou R. and Loonen H. Editors (2000). EuropeanUnion Risk Assessment Report: Benzene, C10-13-alkyl derivs. Luxembourg:Office for Official Publications of the European Communities. 1st PriorityList, Volume 3. EUR 19011. ISBN 92-828-8452-X.

Contacts

Head of UnitGerald VollmerTel.: +39 0332 789983Fax: +39 0332 789963gerald.vollmer@jrc.it

New ChemicalsBirgit Sokull-KluettgenTel.: +39 0332 785849Fax: +39 0332 789184birgit.sokull-kluettgen@jrc.it

Existing ChemicalsBjorn HansenTel.: +39 0332 785884Fax: +39 0332 789963bjorn.hansen@jrc.it

Testing MethodsJuan Riego SintesTel.: +39 0332 785987Fax: +39 0332 789963juan.riego-sintes@jrc.it

Classification and labellingElisabet BerggrenTel.: +39 0332 789065Fax: +39 0332 789963elisabet.berggren@jrc.it

Export ImportElisabet BerggrenTel.: +39 0332 789065Fax: +39 0332 789963elisabet.berggren@jrc.it

Jose Sala BenitoTel.: +39 0332 785735Fax: +39 0332 789963benito.sala@jrc.it

BiocidesKirsten RasmussenTel.: +39 0332 785344Fax: +39 0332 789963kirsten.rasmussen@jrc.it

IUCLID databaseStefan ScheerTel.: +39 0332 785683Fax: + 39 0332 789963stefan.scheer@jrc.it

ECB webpageRemi AllanouTel.: +39 0332 786025Fax: +39 0332 785862remi.allanou@jrc.it

EUROPEAN CENTRE FORTHE VALIDATION OFALTERNATIVE METHODS

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The Validation of Alternative Biomedical Test methods

The European Centre for the Validation of AlternativeMethods (ECVAM) is an international reference centrefor the independent evaluation of the reliability and rel-evance (i.e. the validity) of scientifically advancedmethods for predicting particular kinds of toxic hazardand for quality control and safety assessment.

The emphasis is on test procedures, test batteries andintegrated testing schemes, which could reduce, andeventually replace the need for tests on laboratory ani-mals.

This involves the development and evaluation of in vitromethods (cell and tissue cultures), and the use of com-puter modelling based on structure-activity relation-ships and physiological and biokinetic modelling. ECVAMhas a wide network of collaborators in academic, industryand government laboratories in the Member States andall over the world and works in close collaboration withDG ENV, DG ENTR, and DG SANCO.

Validation

Serious decisions must be taken about the potentialeffects of various kinds of chemicals and products,therefore the validation of new methods requires a formalprocess, usually involving the blind testing of codedtest items in a number of laboratories, with independentselection and coding of these items and independentcollection and analysis of the test results. This part ofthe process is preceded by confirmation that a methodhas been satisfactorily developed to meet certain crite-ria, and a prevalidation stage to assure that an opti-mised test protocol is available and can be transferredfrom one laboratory to another. It is followed by anindependent evaluation of the outcome of the valida-tion stage (e.g. by the ECVAM Scientific Advisory Com-mittee – ESAC), then consideration by the appropriateregulatory bodies in the Commission and the MemberStates.

June 2000 was a historic month for alternative methods,since three in vitro methods (two for skin corrosivityand one for phototoxic potential), validated in studiessponsored or managed by ECVAM, were accepted by theEU Member States as Annex V test guidelines in relationto Directive 67/548/EEC. Meanwhile, the ESAC endorsedthe local lymph node assay for skin sensitisation, theEpiDerm and Corrositex skin corrosivity tests and two invitro tests for tetanus vaccines for human use as scien-tifically validated methods, and ECVAM formal valida-tion studies showed that three in vitro tests for embryo-toxicity and an in vitro test for acute neutropenia hadmet the validation criteria.

Metabolism and Neurotoxicity

Many chemicals which enter the body are metabolicallymodified, especially in the liver, to produce more toxicor less toxic compounds. Anticipation of such metabolismand an evaluation of its possible effects is a vital partof pre-clinical studies on drug metabolism.

A prototype for an innovative medium throughputHPLC/MS system for measuring metabolism related en-zyme activities has been developed at ECVAM. Two grant-holders, associated with this task, obtained their PhDsat the universities of Konstanz and Nottingham. Thefirst attempt to apply a JRC patented system involvinggenetically engineered neuronal cell lines led to anaward for the ApomenCellCheck Kit.

European Centre for the Validation of Alternative Methods

cevam Web Information resources

At IHCP site:http://ihcp.jrc.it/TheIHCP/Activities/ACTVali.html

ECVAM – Scientific Information Services (SIS)http://ecvam-sis.cec.eu.int/

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Reprotoxicity and Cardiotoxicity

The potential of chemicals and products to damage thedeveloping embryo and foetus is a major problem. Thesuccessful results of prevalidation/validation studies onthe subject, and the related publication in ATLA (Alter-natives to Laboratory Animals) in 1999, resulted in 2000in an award for the best paper of the year.

The same working group was involved in the successfulvalidation of the embryonic stem cell (ESC) test. In thistest, embryonic bodies are created in vitro, which arecomposed of beating cardiac cells, haematopoietic cells,muscle cells or nerve cells. The ability of chemicals to af-fect the differentiation of cells derived from ESC alongspecific pathways can thus be evaluated. Research atECVAM is focused on the production of genetically ESCs,in order to develop an effective high-throughput system,and on the development of more sophisticated endpointsto provide answers to mechanistically relevant questions.

Metal Toxicity

Trace metals and their compounds play a crucial role inmany biological systems, and their possible harmful ef-fects (induction of toxic, mutagenic and carcinogeniceffects) are addressed in a series of Directives (80/778,80/1107, 87/416, 89/458, 91/441), which define thelimits for the daily intake for trace metals present in theenvironment and for threshold limit values in the work-place.

An external contract has been awarded for the develop-ment of a test for metal induced infertility and spermio-toxicity and active collaboration has been establishedwith other task groups, on the absorption of metals byCaco-2 cells (an in vitro model of intestinal absorption)on the embryotoxicity of metals.

Nephrotoxicity, Barriers and Long-Term Toxicology

Cellular barriers play an important role in many organsof the human body by regulating the uptake, transportand secretion of endogenous and foreign chemical sub-stances. Modifications to these barriers can result inexposure to various types of chemical substances. Invitro tests are being developed at ECVAM and with col-laborators, for detecting toxicity to various barriers,e.g. the renal epithelium, the intestinal epithelium, theblood-brain barrier and the skin after short and longterm exposure to potential toxicants.

The Tecnomouse system for long-term studies in vitrohas been successfully transferred to ECVAM by contract,thus permitting long term chronic toxicity studies oncells which can be maintained for months without sub-culturing.

A multi-system for transepithelial resistance has beenoptimized and has been used in the development ofscreening procedures for the rapid and reliable detec-tion of toxic effects induced in the renal epithelium bychemicals.

HPLC and luminescence methods for nucleotide meas-urements have been developed in-house and optimized,as a basis for defining new test endpoints.

Activities concerned with uptake across the intestinalbarrier focused on the use of CaCo-2 cell line, in collab-oration with various external collaborators, and an ex-ternal contract was awarded in 2000.

Haematotoxicity and Anti-Cancer Drugs

The bone marrow, a major part of the blood forming sys-tem, is the target for a wide variety of industrial and en-vironmental chemicals, and damage to blood cell forma-tion is a major side effect of anticancer drugs. Theavailability of in vitro testing for evaluating the conse-quences of exposure to medicines or other chemicalssubstances in the various blood-cell lineages is soughtfor within the frame of ECVAM’s activities.

The final report on the successful validation studies onthe CFU-GM clonogenic in vitro test for acute neutropeniais being prepared for publication. The first stage of astudy on the prevalidation of the CFU-MK in vitro assayfor the prediction of thrombocytopenia has been com-pleted.

An evaluation of techniques for the use of human bone-marrow cells as precursors for blood cell lines has takenplace, and a number of techniques have been refined.Standard operating procedures for the use of human cordblood cells in clonogenic assays have been produced.

Biologicals

Biologicals are products such as vaccines, immunosera,immunoglobulins, hormones, monoclonal and polyclo-nal antibodies. The quality control and safety testing ofbiologicals still require the use of large numbers of ani-mals; even though some advanced in vitro tests alreadyexist for some of these purposes. ECVAM is a partner inor sponsor of a number of prevalidation and validationstudies on methods for the quality control of immuno-biological and hormones.

The scientific validity of methods for tetanus vaccinesfor human use was endorsed at the December 2000 ESACmeeting. The report of ECVAM Workshop 41 (ATLA 28,241-258, 2000) on Three RS approaches in the productionand quality control of avian vaccines, is already having avery significant effect at the European regulatory level.

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Computer modelling

Computer based systems for predicting toxic effects areof increasing value and significance. Structure-activityrelationships (SAR) have been developed to predict thepotential of chemicals to cause skin corrosion, eye irri-tancy, acute neurotoxicity, etc.: an important contribu-tion to the derivation of SAR for predicting the cornealpermeability of chemicals and pharmaceuticals has beenpublished in 2000. Interaction with other groups hasled to the improvement of a number of prediction models,e.g. in embryotoxicity and cardiotoxicity testing. APh.D. was gained at John Moores University, Liverpool.

Biostatistics and Experimental design

The highest possible standards of experimental design,and independent data retrieval and analysis, are crucialto ECVAM’s work as a recognized validation agency.ECVAM’s biostatistics task force has been re-formed andECVAM’s role is being supported more strongly. An externalcontract for a review of statistical methods applicationto prevalidation/validation studies has been awarded. APhD on evaluation of research involving transgenic ani-mals was gained at the University of Nottingham.

The ECVAM Scientific Information Service (SIS)

In 1996, a unique scientific information service (SIS)was established to disseminate information (factualand evaluated) on advanced alternative methods fortoxicology assessment. It provides full method descrip-tions, including their development and validation sta-tus. Furthermore, detailed protocols for their use, testcompounds to which they have been applied, and testresults and information on user laboratories are madeavailable.

Selected databases have been prepared for online distri-bution via the Internet. Furthermore, the total informa-tion content of SIS is being updated, with the definitionof data sheets on reproductive toxicity, hepatotoxicity,metabolism-mediated toxicity and percutaneous absorp-tion, as well as with the definition and entry of newprotocols. An international ESAC subcommittee, createdespecially for SIS, met for the first time in Decemberand reported the progress, made to the ESAC. A prelimi-nary version of the thesaurus on alternative methods, aproject of the ECVAM Task Force on databases, has circu-lated for comments.

Cosmetics and Human Volunteer Studies

An external contract is being awarded to provide stand-ardized protocols for the safe and ethical use of non-invasive measurements in human volunteer studies, as abasis for comparing in vitro tests and human in vivo testdata.

Shared Cost Actions

Comparison and Validation of Novel Pyrogen Tests Basedon the Human Fever Reaction Pyrogen testing is a crucialaspect of the control of medicinal products, as well as ofinnovative high-tech products such as cellular therapiesand species-specific agents (e.g. recombinant proteins).For biologicals, especially blood-derived drugs, a rabbittest still represents the method of choice, requiringhundreds of thousands animals in the EU per year. Thistest is laborious, expensive, raises ethical concerns andcannot be applied for some of the new products. In recentyears, in Europe, a number of alternative cellular assayshave been developed, exploiting the human fever reac-tion. The network brings together the most prominenttest systems for trans-national comparison and subse-quent validation of the most promising models.

The Innovative Project Competition launched in July 2000by the Co-operation Strategy and Technology TransferUnit for JRC researchers, led to an award for the Apo-menCellCheck project. The project on the optimizationof genetically engineered cell lines for the identificationof apoptosis-mediated neurotoxicity, aims to designand develop a test kit (Apomen Cell Check), which canscreen in a fast, reliable and technologically and mech-anistically relevant manner, for apoptosis-mediatedneurotoxic effects. The project embodies elements oftechnology transfer to industry.

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Other

A management manual has been produced as a day-to-day working guide for all ECVAM staff, incorporatingelements such as Good Laboratory Practice, Good CellCulture Practice, QA, Safety and Project Management.

The 1800 page proceedings of the 3rd World Congress onAlternatives and Animal Use in the Life Sciences (Bologna1999) were published in October 2000 by Elsevier BV,Amsterdam.

In the frame of the PECO projects, ECVAM has receivedfunds for the promotion of advanced and alternativetesting methods, including development and applica-tion, throughout, and in collaboration, with the candi-date countries. The programme is already being imple-mented. Training days, short permanence periods andworkshops conferences to be hosted in candidate coun-tries and at the IHCP are envisaged.

Publications 2000

Coecke S., Catalani P., Bull S., Langezaal I., Bogni A., Bremer S. and Balls M.(2000) The integrated use of a genetically engineered cell line panel har-bouring drug metabolising enzymes to detect metabolism-related problemcompounds. In “Progress in the Reduction, Refinement, and Replacementof Animal Experimentation” (eds. M. Balls, A.-M. van Zeller and M.E. Halder),pp. 147-157. Elsevier Science, Amsterdam, The Netherlands.

Delpire V.C., Mepham T.B. & Balls M. (2000) Proposal for a new ethicalscheme addressing the use of laboratory animals for biomedical purposes.In “Progress in the Reduction, Refinement, and Replacement of AnimalExperimentation” (eds. M. Balls, A.-M. van Zeller and M.E. Halder), pp.841-849. Elsevier Science, Amsterdam, The Netherlands.

Gribaldo L. (2000) Haematotoxicology in drug development: a model ofhuman toxicology. In “Progress in the Reduction, Refinement, and Replace-ment of Animal Experimentation” (eds. M. Balls, A.-M. van Zeller and M.E.Halder), pp. 671-677. Elsevier Science, Amsterdam, The Netherlands.

Gribaldo L., Malerba I., Collotta A., Casati S. and Pessina A. (2000) Inhi-bition of CFU-E/BFU-E by 3’-Azido-3’-deoxythymidine, chlorpropamide,and protoporphirin IX zinc (II): a comparison between direct exposureof progenitor cells and long-term exposure of bone marrow cultures.“Toxicological Sciences” 58, 96-101.

Janusch-Roi A., Libowitz L. Grüne B. & Kreger M. (2000) Alternativemethod databases - specialised information sources on alternatives tosupport scientists and authorities responsible for granting project licences.In “Progress in the Reduction, Refinement, and Replacement of AnimalExperimentation” (eds. M. Balls, A.-M. van Zeller and M.E. Halder), pp.1731-1736. Elsevier Science, Amsterdam, The Netherlands.

Prieto P. (2000) ECVAM’s in-house prevalidation/validation studies in theareas of haematotoxicity, reproductive toxicity, metabolism-mediatedtoxicity and epithelial barrier function. “The Science of the Total Environ-ment” 247, 349-354.

Worth, A.P. & Cronin, M.T.D. (2000) Structure-permeability relationshipsfor transcorneal penetration. “ATLA” 28, 403-413.

Zuang V., Archer G., Rona C., Vignini M., Mosca M. and Berardesca E.(2000) Predicting visual assessment of allergic patch test reactions bynon-invasive measurements. “Skin Pharmacology and Applied Skin Physio-logy” 13, 39-51.

Contacts

Unit HeadMichel BallsTel.: +39 0332 785996Fax: +39 0332 785336michael.balls@jrc.it

Barriers, Chronic Testingand NephrotoxicityPilar PrietoTel.: +39 0332 785334Fax: +39 0332 785336maria.prieto-pilar@jrc.it

Haematotoxicity andanti-cancer drugsLaura GribaldoTel.: +39 0332 789278Fax: +39 0332 785336laura.gribaldo@jrc.it

Metabolism and NeurotoxicitySandra CoeckeTel.: +39 0332 789806Fax: +39 0332 785336sandra.coecke@jrc.it

Analytical ChemistrySalvador FortanerTel.: +39 0332 785079Fax: +39 0332 785336salvador.fortaner@jrc.it

Metal Toxicity andCarcinogenicityEnrico SabbioniTel.: +39 0332 789070Fax: +39 0332 785994enrico.sabbioni@jrc.it

Cosmetic Safety andHuman StudiesValérie ZuangTel.: +39 0332 785996Fax: +39 0332 785336valerie.zuang@jrc.it

Information servicesAnnett Janusch RoiTel.: +39 0332 785570Fax: +39 0332 785336annett.janusch-roi@jrc.it

BIOMEDICAL MATERIALSAND SYSTEMS

bmsThe Biomedical Materials and Systems (BMS) Unitgroups experts in material science, surface engineering,nuclear and optical techniques, applicable to a broadrange of health related issues, in particular in the areasof biocompatible implants, medical imaging technology.The above focus is based on the demands of an ageingEuropean population and consumer insistence on toolsfor early diagnosis and better planning of therapies. Inparticular, diagnostic tools that lead to the minimiza-tion of surgery are needed for improving patient careand cost effectiveness of public health care systems.

Specifically, the work in these areas encompasses thefollowing main priorities:

• Performance testing of biomedical devices in supportof harmonization of test methodologies on releasefrom and performance of orthopaedic and dental im-plant materials and medical devices under clinicallyrelevant conditions using a combination of advancedtechniques, in support of Directive 93/42/EEC. Func-tional materials and systems, involving the develop-ment and characterization of biocompatible and bio-active surfaces to improve haemocompatibility ofcardiovascular grafts, stents, catheters, and osteo-integration of hip and knee replacement prostheses.

• Minimally invasive medical systems including nuclearand optical imaging techniques. This involves, amongstother activities, the contribution to the developmentof standards for the distribution of radiotracers, andthe participation in European Networks.

Highlight:

Installation of the Fluorodeoxyglucose (FDG) productionfacility at the Cyclotron premises. The module, completewith target, synthesis module, quality control unit can de-liver about 40 GBq at the end of each run. Clean rooms(class C and B) are also available for handling the tracersand to comply with GMP guidelines related to radio phar-maceutical production.

Additional 2000 highlights:

• Launch of the European Thematic Network for OpticalMethods of Medical Diagnosis and Monitoring of Diseases(MEDPHOT).

• Pre-normative research in support of the Nickel Direc-tive 94/27 was carried out; with the definition andpublication of selected test methods (EN 12472) beingadopted by the European Committee for the Standard-ization (CEN).

• A novel plasma source has been developed to allowPVD deposition of biocompatible films inside tubes,for example catheters.

• During the year it has been decided to phase out theactivities on release from consumer products and toconcentrate the activities on biomaterials, as de-scribed above. Reorganization and prioritization ofactivites led to a new project structure with 2 majorproject lines: Reliability of Biomedical Devices andMinimally Invasive Medical Systems.

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Biomedical Materials and Systems

Web Information resources

At IHCP site:http://ihcp.jrc.it/TheIHCP/Activities/ACTReli.htmlhttp://ihcp.jrc.it/TheIHCP/Activities/ACTRadi.html

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Reliability of Biomedical Devices

Increased average life expectancy implies that criticalbody parts (e.g. bones, joints) will wear out and mayneed to be replaced. Biomedical devices or implants,engineered from biomaterials, and designed to performspecific functions now play a major role in replacing orimproving the function of every major body system(skeletal, circulatory, nervous, etc.) and include dentalimplants and orthopaedic devices such as total kneeand hip joint replacements, spinal implants or bone fix-tures. From a regulatory point of view, acceptance of awide range of medical devices at a European Levelrequires the validation and harmonization of testingand characterization methods for the systems and thematerials used. Providing Commission services (e.g.,Enterprise DG, Health and Consumer Protection DG)with scientific and technical information related to theimprovement of standards is necessary and is the ra-tionale behind the project entitled “Reliability of Bio-medical Devices” (REMED Project.)

Biomaterials Processing and Coatings

Many of the problems related to medical implants andprosthetic devices are associated with the interface be-tween biomaterials and biological tissues, bones, etc.The main issue is the behaviour of the host tissues withrespect to an implant material and the ability of thismaterial to fulfil its function in the in vivo environment.The study of interfacial phenomena provides guidancefor the selection of materials and suggests that surfacemodifications may improve the host response to the bio-material. Methods are being developed at the IHCP tostudy bio film formation on medical devices, prostheses,or tooth surfaces, and to define improved or new strate-gies for their safe use while ensuring adequate long termoperation.

Carbon thin films have been deposited with a MicrowaveAssisted PVD reactor (financed by Competitive Supportprogramme of DGXII: project IRDEC). The reactor hasbeen intensively tested and carbon films with a control-lable diamond character have been deposited. Biocom-patible diamond-like carbon films are deposited on NiTialloys used in stents, bone sutures and orthodontic ap-pliances as protective coatings to avoid nickel migration.

Nacre coatings have been considered for biomedical im-plants in the framework of a competitive action. Nacreis a compound found in nature on the inner surfaces ofoyster shells. 3 different types of nacre coatings havebeen Plasma sprayed on several substrates as well aship joints and dental implants. Osteoblast cells havebeen grown on the ceramic before and after spraying, aswell as Titanium and PE sheets. Results demonstrate theosteoinductive property of the nacre before sprayingand after spraying. The clear advantage of the coatingsover pure Titanium opens a new route for developmentof biocompatible coatings.

A biocompatible surface can be obtained by covalent im-mobilisation of proteins on the medical devices. Onemethod is to graft aldehyde, carboxylic or epoxy moietieson the surface and to covalently bond the antibodiesthrough their amine functions. We have deposited a func-tional film by plasma polymerisation of acrylic acid va-pour using an inductive plasma source. Preliminary resultsshow that acrylic functionalities can be maintained dur-ing deposition and a thin film of 200 to 1000 nm can bedeposited with strong carboxylic character. Another as-pect of the work was the development of a plasma sourceconfiguration for treatment of catheters, in which a Trans-verse Flux plasma source has been tested and patented.

Performance Testing

Testing of implants under conditions that simulate thespecific clinical use (e.g. under realistic dynamic loads,or in the presence of biological liquids for prolongedperiods of time) is a key issue in validation of lifetimeassessment models and verification of the reliable per-formance of biomedical devices. Pre-normative test de-velopment is needed to identify and evaluate the relevantparameters to be considered by regulators and Industryfor standardisation and to allow the qualification ofnew developments in the field such as the use of newmaterials, including coatings. An additional requirementis the need to ensure the long-term integrity of the im-plants, taking into account potentially harmful materialrelease, likely to cause toxic effects in the human body.

In support of Directive 93/42/EEC, pre-normative testingfor hip and knee implants was undertaken at the IHCP.Development of pre-normative testing methods, includ-ing the effect of different biological lubricants on wearand corrosion, has been pursued.

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A 2-axis dynamic loading 3-station hip joint simulator,suitable for pre-normative research, was developed andconstructed. Test programmes with up to 3 million simu-lated walking cycles were performed. Preliminary com-parisons with various screening wear facilities indicatethat the ranking of materials tested with a simple screen-ing wear facility can be very different from that testedwith the simulator. For highly sensitive on-line monitor-ing of wear, Thin Layer Activation (TLA) was employed.In view of ISO TR9326, regarding the use of TLA for wearof polymers, a collaborative study on possible radiationdamage in various medical grade polymers was performed.The feasibility of the use of a special TLA technique forthese types of materials was proven. Considering biologi-cal effects of wear particles, procedures for isolation ofwear particles from biological solutions after testing arebeing developed in collaboration with ECVAM.

In view of the increasing number of clinical cases report-ing metal allergies related to implants and the signifi-cant difficulties to determine small amounts of releasedmetal, the use of TLA was further improved. Preliminaryresults indicate that detection limits can be sufficientlylow even in complex biological environments. Thus themethod can serve as a reference for conventional methods.A special activation technique to improve the sensitivityby a factor 10 is presently under development. The elec-trochemical test facilities were complemented with theinstallation of a scanning reference electrode device,enabling the study of local corrosion phenomena. Dueto the increasing interest of surface treatments for po-tential application in medical implants, some systemswere included in wear testing and electrochemical char-acterisation, including alumina layers and functionallygraded ceramic materials (2 related SCAs).

The IHCP carries out research on release due to surfacedegradation of materials and devices under practicallyrelevant conditions, using a combination of advancedtechniques. In particular, highly sensitive electrochemicaland nuclear (i.e. radio-tracer) analytical methods canbe applied to measure the release of compounds duringsimulation of practical use. These studies are aimed atproviding reference measurements to be used in bench-marking tasks, for instance, to qualify analytic chemistrymethods on its progression towards validation studies.

Material release from orthodontic materials is of in-creasing concern. The situation is rather complex in viewof the wide range of materials (more than 5000 in Eu-rope) being used in orthodontic applications; the vary-ing clinical conditions during use and the absence ofreference test procedures. An activity has been initia-ted on the release of dental systems. Emphasis will be oncoupling of dissimilar materials. The feasibility of usingradiotracers to measure the release of certain elementswas studied. This also forms part of a follow-up of a DGEnterprise ad hoc committee on dental amalgams.

A feasibility study was done for the establishment of aregister for prosthetic devices and surgical techniques.The main scope is to collect data on surgery and follow-up of implants from the pre- and post-operative situa-tion and to set up a data bank, allowing a statisticalanalysis of the performance of different types of pros-thesis and surgical techniques. This work will be contin-ued in future in coordination with DG SANCO. It supportsthe harmonisation of databases on the reliability ofmedical devices, as a first step towards the establish-ment of European registers of implants.

Minimally Invasive Medical Systems

Minimally invasive medical systems are being developedbased on radioisotope and optical methods. Radiotra-cers will play an increasingly important role in medicaldiagnosis and therapy. As a diagnostic tool they enablethe imaging of physiological tissue functions and revealpossible malignant alterations. This functional imaginguses radionuclide-labelled biomolecules that are involvedin the metabolism of the tissue under examination. Theradiation emitted by the label can be detected outsidethe body and is used to image the distribution and in-tensity of physiological processes. Positron EmissionTomography (PET) obtains the highest resolution andaccuracy.

The enormous potential of PET in clinical practice andmedical research as well as emerging radionuclide ther-apies for dispersed and inoperable cancers will lead to astrongly increasing demand for radiopharmaceuticals.An increased cost-effectiveness in the management ofcancer patients and the medical and economic advan-tages of less invasive treatment of several groups of dis-eases will promote this development.

The BMS Unit has initiated activities in these areas inthe 5th Framework Programme under the work pro-gramme Medical Imaging and Therapy using Radiotra-cers (MIMES). The programme encompasses several tasks,including the production of medical radioisotopes, sup-port for their use in cancer therapies, and the validationof methods applied in medical imaging.

The technical issues in medical imaging concern proto-cols and guidelines for data acquisition and analysis,which have to be optimized to assure the highest qualityof the final examination and reproducibility and relia-bility of the results. This applies to imaging with PETin particular for the development, implementation andvalidation of models of tracer kinetics, which aim at areduction of the time, required for PET scans and an op-timization of the sensitivity. Similar issues are impor-tant in the field of optical methods for medical diagnosis,which use laser light for morphological and functionalimaging.

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The production of radioisotopes for research is per-formed in collaboration with universities, hospitals andother research centres. Commercial production aims atacquiring practical knowledge in the field of qualitycontrol at all stages of production and on the technicalissues of the distribution and delivery of short-lived ra-dioisotopes to hospitals and research organizations.This knowledge is of strategic importance, given thelack of Europe-wide regulations for the production anddistribution of PET radiopharmaceuticals, which hindersthe development of a common market and the distribu-tion of PET facilities in clinical centres without their owncyclotrons. Such technical issues must be considered forfuture European regulations on radiopharmaceuticals.For this purpose, contacts have been established withthe European Agency for the Evaluation of MedicinalProducts (EMEA) in order to clarify the legal aspects forthe production and distribution of radiopharmaceuticals.

In order to establish a programme for anti-cancer therapyusing α-emitting radioisotopes, studies of the evalua-tion of interest and resources have been performed. Inparticular, the IHCP reviewed the current state of the artin production technologies for 211At. An improved targetfor 211At production has been constructed and is beingproduced. The new target is expected to allow efficient211At production at high α-pitch current to produce rel-evant quantities for cancer therapy research.

The production of 123I for diagnostic purposes has beencontinued at the IHCP cyclotron in 2000 as Third PartyWork. The installation of the target and the productionmodule for FDG (2-deoxy-2[18F]-fluoro-D-glucose) wasfinished in December 2000 and the module can start de-livering about 40 GBq of FDG at the end of each run,starting in January 2001.

The use of laser light enables morphological and func-tional imaging in vivo as well as non-invasive or mini-mally invasive therapeutic techniques. The work in 2000resulted in the establishment of a partnership leadingto a European Thematic Network dealing with “OpticalMethods for Medical Diagnosis and Monitoring of Diseases”with IHCP-BMS as network manager. Mathematicalmethods which had been developed at the JRC in thecontext of studies on reactor safety, radiation shieldingand light transport in air-water systems have been re-viewed and work has been started on the conversion ofexisting computer codes for the description of lightpropagation in biological tissue. This allows the im-provement of computer models for the optical charac-terization of biological tissue based on Monte CarloSimulations and Diffusion Theory.

Publications 2000

C. Brugnoni, R. Bianchi, A. Bianchini, M.F. Stroosnijder, “Influence ofexperimental test conditions on the Ni release of a Cu-Ni alloy in artificialsweat”, in Materials for Medical Engineering, H. Stallforth and P. Revell(eds.), Wiley, 2000, pp. 237-242.

K. Abbas, D. Gilliland and M.F. Stroosnijder, “Radioactivity measurementsfor the thin layer activation tech-nique”, Applied Radiation and Isotopes,53(2000) 179-184.

D. Gilliland, K. Abbas, M.C. García Alonso and M.F. Stroosnijder, “Applicationof TLA radiotracers to measuring the release of metallic allergens from medicalimplants”, in Materials for Medical Engineering, H. Stallforth and P. Revell(eds.), Wiley, 2000, pp. 210-216.

P.N. Gibson, M.E. Özsan, D. Lincot, P. Cowache and D. Summa, “Modellingof the structure of cds thin films”, Thin Solid Films, 361-362 (2000) 34-40

P.N. Gibson, “Thin films: characterization by x-rays”, Encyclopaedia ofMaterials: Science and Technology, section 2.8, article no. 73, eds. K.H.J.Buschow, R.W. Cahn, M.C. Flemings, B. Ilschner, E.J. Kramer and S. Mahajan,Pergamon (Elsevier Science).

P. Colpo, G. Ceccone, P. Sauvageot, M. Baker, and F. Rossi, “Characterizationof Zirconia Coatings Deposited by Inductively Coupled Plasma AssistedChemical Vapour Deposition”, Journal of Vacuum Science and TechnologyA18(4), 1096-1101, 2000.

F. Rossi, “Amorphisation and growth mechanisms of carbon films under ionbeam irradiation”, in Nanomaterials, Pergamon June 2000 ISBN: 0-444-50345-5 Ed. Mitura.

Contacts

Head of UnitHermann StammTel.: +39 0332 789030Fax: +39 0332 785388hermann.stamm@jrc.it

Reliability of Biomedical devicesFrancois RossiTel.: +39 0332 785443Fax: +39 0332 789169francois.rossi@jrc.it

Rien StroosnijderTel.: +39 0332 785281Fax: +39 0332 789385rien.stroosnijder@jrc.it

Minimally Invasive Medical SystemsNeil GibsonTel.: +39 0332 785616Fax: +39 0332 785036neil.gibson@jrc.it

SUPPORT TO PHARMACEUTICAL RESEARCH

Telematic systems for the EU Pharmaceutical regula-tory activity

The regulatory procedures necessary to assure efficacyand safety of medicines (including vaccines, blood de-rivatives, radiopharmaceuticals etc.) require a combina-tion of information/communication systems to supportthe essential Europe wide co-operation.

IHCP is a well-established R&D provider for the studyand development of these information/communicationtools (including data models and application protocols).The work is carried out in collaboration with DG ENTR,the European Agency for the Evaluation of MedicinalProducts (EMEA), National Agencies and the Pharma-ceutical Industry.

The IHCP has developed a number of information/com-munication systems: the Eudratrack Mutual Recognition(EMR- developed taking advantage of the EudraNET net-work, adopted by all pharmaceutical and veterinary au-thorities) supporting decentralised applications and theEudraNet services supporting authorization for the entiremarket and post-market control.

In the current workprogramme, IHCP is pursuing the up-grade of the EudraNet network, incorporating advancednetwork services (such as EudraSafe) and the develop-ment of a Unified Tracking System (UTS), integrating bothmarketing authorization procedures and EMR and primarytracking systems (ATS) in order to track all types of mar-keting authorization procedures and to monitor impropersubmission. The implementation of an information dis-semination application (Medicines Information Networkfor Europe – MINE) based on a central database on allauthorised medicinal products is also pursued.

All these new services focus on secure communicationover the public network, including the document deliveryand the distributed co-operative environment amongEMEA, the Commission services and the National Author-ities, assigning the JRC a central role as data managerof the EU portal for all authorized medicinal products onthe market.

Taking into account the objectives to be pursued, theneed for focussing the IHCP activities and increasingrequests from customers, it has been decided to cancelall activities running in the Unit (e.g. on electroniccommerce etc.) except those in support of the pharma-ceutical regulations, re-allocating all resources accord-ingly.

EudraTrack Mutual Recognition (EMR) system

The EMR system is presently established as the officialtool shared by Member States regulatory authorities –17 for human products, 17 for veterinary and two forvaccines and blood products. This permits a first deci-sion on the granting, suspension, withdrawal or amend-ment of a marketing licence to be made in one MemberState (the “Reference”)(RMS), which then submits thedata using EMR to other “Concerned” Member States(CMS) as a basis for reaching mutual recognition at anEU level. EMR handles new applications, variations, re-newals and extension of approvals; it stores a descrip-tion of the product and records the actions of Referencestates and the comments and requirement of Concernedstates throughout every stage of the authorization pro-cedure. EMR contains a number of services to facilitateretrieval and dissemination of information, includingreporting, alerting and query system as well as e-mailgeneration. It handles about 350 new events each day.In 2000 the system was upgraded with faster query tools.

In addition, the TSE issue has been considered.

Unified Tracking System (UTS)

This telematic application for marketing authorizationand post-marketing management of medicines combinesthe results of ATS and EMR in a single innovative systemand represents a milestone towards the development ofa common standard tracking system for the pharmaceu-ticals sector. The first prototype was presented in 1999,allowing UTS users to trace the processes of authoriza-tion and evaluation of medicinal products. In 2000, anew classification into five levels of MA applicationshas been introduced (i.e. new active substance, initialapplication, full dossier, herbal and prescription). More-over, the procedure header is now editable, allowing the

42

sprSupport to Pharmaceutical Research

Web Information resources

At IHCP site:http://ihcp.jrc.it/TheIHCP/Activities/ACTPhar.html

update of the contents of the following fields (e.g.CMSs, MA holder, Product name, Active substances, Phar-maceutical form, ATC code and RMS contact).

Medicine Information Network for Europe (MINE1)

MINE is a network-based application which aims to es-tablish a coherent, comprehensive European Data Centreto provide official information about human and veteri-nary medicinal products authorized in the EU in accord-ance with Council Regulation No. 2309/93. it offersstructured and standardized information about the effi-cacy and safety of medicinal products marketed in the EU.The medicinal product database, complemented withthe document base providing related official public docu-mentation (EPARs, SPCs, PILs, scientific discussion, etc.),has embedded knowledge that allows intelligent, com-plex retrieval of information. As soon as the process forcollecting all information for all authorization proceduresin the UTS database is finalized, the MINE system willbecome the first European wide socio-economical systemdedicated to public health and consumer protection.

EudraNet Network services

Both UTS and MINE1 services are implemented on top ofa new generation of network services offering advancedworkgroup collaboration tools such as EudraSafe, whichprovides the capability of secure transfer of confidentialdocuments between users who are not directly connec-ted to the private EudraNet backbone, but have accessto Internet services; DVC (Desktop Video Conferencing);and e-Room, a conferencing and file sharing system. Atthe same time, studies are underway for the next phaseof Eudranet, known as Eudranet 2, which will make useof cryptography based security services to implement asecure data communication network in the form of oneor more private tunnels over a public network.

Specific events

Training Course provided to EudraTrack users, held in London - June 19-21and June 27-28.

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Publications 2000

V. Pagliari and A. Rana: “The Unified Tracking System (UTS) - MedicinalProduct Data Model”, Technical Note I.00.142, December 2000.

A. Rana and F. Argentesi: “Medicine Information Network for Europe: deliver-ing to consumers information about medicinal products authorised in theEU”, to be presented at the “eHealth: a Futurescope” the 3rd InternationalConference on Advances in the Delivery of Care, London, April 4–6, 2001.

S. Sanfelici, A. Rana: “A survey on Electronic Payment Systems”, SpecialPublication No. I.00.88, June 2000.

V.Pagliari and C. Bartolini: “EudraTrack Mutual Recognition – User’s Manual– version 5.2.16”, Special Publication No I.01.20.

Contacts

Head of UnitFlavio ArgentesiTel.: +39 0332 789249Fax: +39 0332 786187flavio.argentesi@etoit.eudra.org

EudraTrack Mutual Recognition SystemValerio PagliariTel.: +39 0332 785177Fax: +39 0332 789265valerio.pagliari@etoit.eudra.org

Unified Tracking SystemValerio PagliariTel.: +39 0332 785177Fax: +39 0332 789265valerio.pagliari@etoit.eudra.org

Medicine Information Network for EuropeAntonia RanaTel.: +39 0332 785478Fax: +39 0332 789256antonia.rana@jrc.it

EudraNet Network servicesAntonia RanaTel.: +39 0332 785478Fax: +39 0332 789256antonia.rana@jrc.it

Networking - Examples

2000 Performance Indicators

International Olive Oil Council (based in Spain).MS Public Bodies: Instituto de la Grasa - CSIC.IGS (E). Institutode las Fermentaciones Industriales - CSIC-IFI. CSL (UK).Nat. Hellenic Research Fondation (GR). Dep. Qualite ProduitsAgricoles (B). Istituto Sperimentale Elaiotecnica (I). StazioneSperimentale Oli e Grassi (I). CNR-Istituto Chimica Nuclear (I).Industry: Eurofins (F). Andoleum (S).Universities: Univ. Agricultural Sciences-Vienna (A). Univ. CatholiqueLouvain (B). Univ. Complutense Madrid (E).

MEDEO

Industry: Eurofins (F).MS Public Bodies: Bundesinstitut fuer gensundheitlichenverbraucherschutz und veterinaermedezin (D).Central Science Laboratory, Ministry of Agriculture Fisheries and Food (UK).Istituto Agrario di San Michele all’Adige (I).

GLYCEROL

RIKILT (NL), VBF (DK), UDUR.DBS (UK), CEA-Cad (F), EC JRC IHCP(I), IFA-Tulln (A), IFR (UK), RRI (UK), UNILEVER (UK), ISS (I),CEA-SPI (F), IEM (S), BIBRA (UK), TUM (D), Metapontum (I), LEI(NL), TNO (NL), KEPKA (EL), SCRI (UK), RKI (D), ILSI (B), BgVV(D), Agre Vo (UK), IFT (D), EC JRC IRMM (B), BEUC (B), UKU (FIN),AHOLD (NL), Monsanto (B), Nestlé (CH), NVI (N).

ENTRANSFOOD

National Vet Inst (N), MATFORSK (N), INRA (F), DvP-CLO (B), LGC(UK), Gene-Scan (D), TEPRAL-Danone (F), Unilever (NL),Bio-GEVES (F), DGCCRF (F), IFR (UK), CSIC (E).

QPCRGMOFOOD

FOOD

‘MS Public Bodies: National Agricultural Research Centre (B).State Institute for Quality Control of Agricultural Products (NL).Italian National Institute of Health ISS (I).Scottish Agricultural College SAC (UK).Laboratory of the Autonomous Government of Catalonia LAGC (E).State Official Laboratory ROLT (E).Universities: Agronomy Science University FUSAGx (B).School of Agriculture and Forestry Engineering of Univ. of Cordoba (E).Industry: Maasweide Laboratory, Nutreco (NL).

STRATFEED

‘MS Public Bodies: State Institute for Quality Control of AgriculturalProducts-RIKILT (NL).

Staatliche Ladwirtschaftliche Untersuchungs- und Forschungsanstalt-LUFA Augustenberg (D).

Danish Plant Directorate (DK).IZ LUFA ITL - Kiel (D).Direction Generale de la Concurrence, de la Consommation

et de la Repression des Fraudes - DGCCRF (F).Bavarian Departement for Nutrition - LfE Munchen (D).Laboratorio Nacional Investigaçao Veternaria (PT).Instituto Superiore Sanità (I).National Veterinary Institute - Uppsala (S)

SIMBAG-FEED

Lima Lto (I), Ceramtec (D), IMT Bodycote (UK)Hospitals & Universities: Univ. Leuven (B), Helsinki Univ. Technology(Fi).

BIOGRAD

FIAT (I), THOMSOM (F), FHR, EUROINKS.

LAPLADIS

FLUXTRAN

ARJO WIGGINS (F) R BOSCH GmbH (D) METAL PROCESS (F) BIOMATECHS.A. (F) C.I.R.M. (I).

STERIPLAS

ISIS Optronics GmbH, R. Wolf GmbH, STORZ (D).MS Public Bodies: FORTH-ISEL (Gr), PTB-National MetrologyInstitute of Germany, Lund Laser Centre (D).Hospitals & Universities: ILM-Univ. Ulm, Robert-Rossle Hospital-Berlin, Humboldt Univ., MLL-Univ. Lubeck, (F).

MEDPHOT

BIOMED

RELEVANCE: Link with policy legislation.COSTUMER FOCUS: Results of survey among DGs (performed in 2000) • “excellent” evaluation about results provided by IHCP and its impact.

Emergency reactions: • animal feed ban • phthalates.Both cases have shown a very fast and effective response to “crisis” situation.

NETWORKING/COLLABORATIONS/PARTNERSHIP: • Leader in the GMO networks • New SCA started (6 actions formalised, 5 on going)• Coordination for the animal feed ban • Increase of the ECVAM network base.

TRAINING (given): • 4 courses in GMO for WHO (letter of appreciation received) • 2 ECB courses on IUCLID • People from candidate countries on GLP (3 persons, short stays at ECVAM).

PUBLICATIONS: • Monographs/Periodicals: 72 • EUR: 10 • Conferences: 108 • Special Publications: 21.PRIZES/AWARDS: • 1 award for micotoxins • 2 innovative projects • 6 SCA • 1 recognition for TLC method; 1 award for alternatives.PATENTS: • 14 since 1998

European Commission

EUR Report 19909 EN – Institute for Health, and Consumer Protection (IHCP) – Annual Report 2000Editors: G.P. Tartaglia, A. CardinaliLuxembourg: Office for Official Publications of the European Communities2001 – 44 pp. – 21.0 x 29.7 cmScientific and Technical Research seriesISBN 92-894-1332-8

ACKNOWLEDGEMENTS

For the accomplishment of this report the editors would like to thank all the IHCP staff involved.Our special thank goes to Orla Hurley, whose prompt contribution was essential.

The editors wish to thank Manuel Florensa and Ramón Sánchez for the graphic design and layout of the report.

More Information

G.P. TartagliaIHCP Management Support UnitHead of UnitInstitute for Health, and Consumer Protection (IHCP)European Commission DG-Joint Research Centre

T.P. 201I-21020 Ispra (Varese) • Italy

Tel: +39 0332 789988Fax: +39 0332 785730

E-mail: giampiero.tartaglia@jrc.it

http://www.ihcp.jrc.it

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The mission of the JRC is to provide customer-driven scientific and technical support for the conception, develop-ment, implementation and monitoring of EU policies. As a service of the European Commission, the JRC functionsas a reference centre of science and technology for the Union. Close to the policy-making process, it serves thecommon interest of the Member States, while being independent of special interests, whether private or national.

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