EUROPEAN COMMISSIONJOINT RESEARCH CENTRE

ISSN 1683-0407

Report EUR 20660 EN

ACTIVITY REPORT2 0 0 2

INSTITUTE FORHEALTH AND CONSUMER

PROTECTION

European CommissionJoint Research Centre (DG JRC)Institute for Health and Consumer Protection (IHCP)TP 202I-21020 Ispra (VA) • Italy

Tel.: + 39 0332 786288Fax: + 39 0332 789059

E-mail: ihcp-contact@jrc.itWebsite: http://ihcp.jrc.cec.eu.int/

EditorM. Hoffmann

Graphic design and layoutJ.J. Blasco & R. Sánchez (cover)Information and Public Relations Unit • JRC Ispra

Legal NoticeNeither the European Commission nor any person actingon behalf of the Commission is responsible for the usethat might be made of the information contained in thispublication.

EUR Report 20660 EN

ISBN 92-894-5312-5

© European Communities, 2003

Printed in Italy

The IHCP is located in northern Italy, on the lakeshoreof Lago Maggiore (Varese province). The nearest city isMilan (approximately 60 km south-east), and the regionis served by Malpensa International Airport, located atabout 30 km from the JRC.

Activity Report 2002Institute for Health and Consumer Protection

EUROPEAN COMMISSIONJOINT RESEARCH CENTRE

CONTENTSForeword 4

IHCP Mission Statement, Scientific Objectives, and End-users/Collaborations 5Executive Summary 6Scientific Highlights in 2002 7The IHCP in Figures–2002 10

IHCP Organisational Chart 12Biotechnology and GMOs (B&GMOs) 13European Centre for the Validation of Alternative Methods (ECVAM) 23European Chemicals Bureau (ECB) 31Physical and Chemical Exposure (PCE) 39Biomedical Materials and Systems (BMS) 47Support to Pharmaceutical Research (SPR) 55

Contributing to the European Research Area (ERA) 58IHCP Performance Indicators–2002 59Competitive Activities (2002)–Examples 60

2002 was a year of significant change for the IHCP. Thischange brought about a need to further re-focus andalign the JRC activities in support of the EU policies, giv-ing the IHCP a key position in the 6th Framework Pro-gramme (FP6).

In the frame of this prioritisation exercise, the activitiesconcerning the support in the access to information onmedicinal products were successfully finalised with theirtransfer to EMEA in London and the Competent Authori-ties of the Member States. Subsequently, the Support tothe Pharmaceutical Research Unit (SPR) ceased to existat the end of 2002.

During the period under review some of the activities ofthe Food Products Unit (FPU) were transferred to IRMM,whereas the GMO related activities were brought under anew Biotechnology and GMO Unit, which has a prime po-sition in the European Network of GMO Laboratories. Thethird change relates to the Physical and Chemicals Expo-sure Unit (PCE), which was created in June 2002 througha combination of existing IHCP activities and projectstransferred from the Institute for Environment and Sus-tainability (IES) and the FPU.

In 2002 the Commission put much effort in developingthe Chemical Policy in which our Institute plays a centralrole. Three out of five scientific Units of the IHCP, namelythe Physical and Chemical Exposure Unit (PCE), the Euro-pean Centre for the Validation of Alternative Methods(ECVAM) and the European Chemicals Bureau (ECB) per-form work in direct support of the EU Chemicals Policy.The activities of these three Units are strongly linked toeach other, while their roles are very different. The primerole of ECVAM is to co-ordinate and fund (pre)-validationstudies while carrying out research in various areas oftoxicology relevant to the testing of chemicals. The tasksof the ECB are focused on the scientific and technicalsupport for developing and improving EU chemical poli-cies by evaluating the risks of chemicals to humans andthe environment. The PCE Unit hosts a multi-disciplinaryteam of researches that combine efforts to reduce the ex-isting deficiencies of human exposure data.

Besides its core activities the IHCP has actively contri-buted in shaping the European Research Area. This hasbeen pursued through extensive networking, such as theEuropean Network of GMO Laboratories, training of scien-tists from the Member States and Candidate Countries.The interdisciplinary nature of the work carried out is al-so a key element in the Marie Curie Training Site BIORAD,which is jointly hosted by ECVAM and the Biomedical Ma-terials and Systems Unit (BMS). This site provides high-level interdisciplinary doctoral training in testing of bio-materials using radiotracers.

In conclusion, I would like to thank the staff of the IHCPfor the continuous support they provided in making ourachievements a valuable contribution to EU policies andEuropean Citizens.

March 2003

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Foreword

Kees Van LeeuwenIHCP Director

The mission of the IHCP is to provide scientific supportto the development and implementation of EU policiesrelated to health and consumer protection. The IHCPcarries out research to improve the understanding ofpotential health risks posed by chemicals, biocides, ge-netically modified organisms, contaminants releasedfrom food contact materials and consumer products.

IHCP’s direct end-users are services within the Euro-pean Commission. Moreover, IHCP collaborates with alarge number of universities, industrial partners, Euro-

IHCP activities focus on the following scientific objec-tives:

• Validation of methods to detect genetically modifiedorganisms (GMOs) in food and feed.

• Development and validation of alternative testingmethods to replace, reduce or refine the use of labo-ratory animals in biomedical sciences.

• Assessment of risks to health and environment fromchemical substances, and management of related in-formation service.

• Evaluation and quantification of exposure to envi-ronmental stressors (such as chemicals, biologicalcontaminants, radiation, and noise).

• Development, validation and use of advanced pro-cessing techniques and test methods for the qualifi-cation of biocompatible materials, medical devices,and health diagnostics.

pean and national authorities, international organiza-tions, and consumer associations (the following is anon-exhaustive list):

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End-users/Collaborations

Customers (within EC) • DG Agriculture, DG Environment, DG Enterprise, DG Consumer Protection (SANCO),DG Research, DG Trade, DG Taxation and Customs Union (TAXUD), DG Enlargement,European Anti-Fraud Office (OLAF)

• DG JRC: EI (Ispra), IRMM (Geel), IAM (Petten), ITU (Karlsruhe), IPTS (Seville)• European Medicine Evaluation Agency (EMEA)

Customers (outside EC) • European Parliament• International organisations (i.e., OECD, WHO, FAO, Council of Europe, European

Directorate for the Quality of Medicines (EDQM))• Interagency Committee for the Validation of Alternative Methods (ICCVAM)• European agencies - Governments (i.e., Competent authorities responsible for the

implementation of biotechnology and novel food Directives; chemical authori-ties, pharmaceutical regulatory agencies in the European Economic Area (EEA),regulatory and health care authorities)

• Non-governmental organisations (NGOs)• Industry (i.e., biotechnology, food and feeding stuff, chemicals, cosmetics, bio-

medical and pharmaceutical)• Consumer Organisations• National Research Institutions and Universities

IHCP Mission Statement Scientific Objectives

The chemicals industry is one of the most importantmanufacturing industries in the EU. Chemical salesalone amounted to 488 billion Euro in 2001 and about3 million people are employed, either directly or indi-rectly, by the Chemicals Industry in the EU. In February2001, the Commission, after consultation with allstakeholders including chemical producers, industrialusers, citizens’ groups and animal welfare organiza-tions, issued a White Paper outlining the chemicals po-licy strategy. Currently the Commission is in the processof establishing a single review and testing systemcalled REACH (Registration, Evaluation and Authoriza-tion of CHemicals) for all existing and new chemicals.

In view of the lack of basic data on industrial chemicalsand the fact that more than 100 000 chemicals stillhave to be tested, the JRC European Chemicals Bureau(ECB) at the Institute for Health and Consumer Protec-tion has continued to put priority on the developmentand validation of methods for continuous improvementin the prediction and assessment of their risks. Thework of ECB is carried out in close collaboration withECVAM, the European Centre for the Validation of Alter-native Methods to animal experiments. ECVAM plays aleading role at the European level in the independentevaluation of the relevance and reliability of tests forspecific purposes (i.e. toxicity assessments of varioustypes of chemicals, quality control and safety assess-ments of biologicals), through research on advancedmethods, new test development and validation, and theoperation of specialised databases.

To rectify the lack of data on human exposure to physi-cal and chemical stressors, which are relevant for riskassessment analysis, the Physical and Chemical Expo-sure (PCE) Unit of the IHCP develops methods for im-proving the monitoring and assessment of human expo-sure to chemicals. Upon request of DG Health andConsumer Protection a European Information System onRisks of Chemicals release from Products and Articleswill be set up (EIS-CHEMRISKS).

Responding to the political and public concerns regard-ing the use of genetically modified organisms (GMOs) infood and feedstuff, the Biotechnology & GMOs Unit ofthe IHCP focuses its work on the development and vali-dation of analytical methods for the detection, identifi-cation, quantification and traceability of GMOs. ThisUnit was created on 1st November 2002 after the trans-fer of the Food Products Unit to IRMM.

In 2002 the Biomedical Materials and Systems (BMS)Unit carried out work characterizing the surface and therelease of potentially hazardous substances from medi-cal devices and consumer products and contributed tothe development of optical and nuclear imaging tech-niques. Its surface modification laboratories receivedinternational recognition for its activities related tothe characterization and modification of interfaces, theimprovement of biocompatibility and functionalizationof surfaces.

The support to the Pharmaceutical Research (SPR) Unitwas stopped in December 2002 after the successful fi-nalization of the transfer of its activities to EMEA andthe Competent Authorities of the Member States.

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Executive Summary

Biotechnology & GMOs Unit

Created in November 2002 the Biotechnology & GMOsUnit is the JRC reference for the provision of scientificand technical support to the EC biotechnology regu-latory framework and develops biotechnology expertisein areas relevant for health and consumer protection.Particular focus is on the development and validationof appropriate methods for detection, identificationand quantification of genetically modified organisms(GMOs) in different types of matrices. Following a natu-ral collaboration between more than 40 EU and PECOenforcement labs under the chairmanship of IHCP, theEuropean Network of GMO Laboratories (ENGL) has beeninaugurated.

In 2002 the Biotechnology & GMOs Unit played a lead-ing role in the QPCRGMOFOOD and the ENTRANSFOODcompetitive projects. To complement the activities, theUnit has decided to embark the INFORMALL concertedaction project, the kick off of which is planned for2003.

European Centre for the Validationof Alternative Methods (ECVAM)

ECVAM plays a key role in the implementation of theNew EU Chemicals Policy in order to minimise the use ofexperimental animals and to speed up the policy imple-mentation throughout the development and validationof more cost-effective and faster in vitro techniques.ECVAM has established an ad-hoc Working group onChemicals with the ultimate goal to propose a strategyon the development and validation of new alternative(non-animal) methods. To best achieve this objectiveECVAM organised several meetings of this workinggroup and its subgroups in 2002, which resulted in thepublication of a comprehensive report, which formedthe basis for the establishment of project managementgroups for all areas of chemical safety testing and theinitiation of a fund of the chemicals industry.

At the same time, ECVAM has initiated, continued or fi-nalised various (pre)validation studies, such as the EC-VAM/ ICCVAM (US Interagency Coordinating Committeefor the Validation of Alternative Methods) validationstudy on acute systemic toxicity, studies for metabo-lism-mediated toxicity, nephrotoxicity and skin irrita-tion testing, as well as in the area of biologicals. In thiscontext, four cell-based tests successfully passed themulti-partner validation project on monitoring side ef-fects, such as fever reactions, arising from contami-nants of injectable drugs. The ECVAM Scientific AdvisoryCommittee issued 6 final statements, this year: three

on the scientific validity of in vitro methods for embry-otoxicity testing as a follow-up of their endorsementsin 2001 and three on potency testing and quality con-trol of vaccines.

In line with its institutional duties, the year 2002 hasseen the consolidation of ECVAM’s scientific informa-tion service (SIS) that reached 1500 active registeredusers to its databases providing factual and evaluated(ready-to-use) information on advanced alternativemethods for toxicology assessments, and ECVAM esta-blished a comprehensive web site about all major activ-ities of the whole Unit.

ECVAM, moreover, continued to extend its laboratory fa-cilities, e.g. with a microarray technology for toxicoge-nomics, i.e. the analysis of gene expressions due to ex-posure to xenobiotics, which might lead to a secondgeneration of alternative methods to animal models.

A major event for ECVAM in 2002 was the Status Semi-nar held in Ispra from 4th to 6th of June 2002 with par-ticipation of stakeholders and main collaborators of theUnit, in addition to the ECVAM and IHCP staff. Further-more, the year 2002 brought changes with regard to EC-VAM’s leadership. Dr. Thomas Hartung was appointed asnew Head of Unit after the retirement of Prof. MichaelBalls.

European Chemicals Bureau (ECB)

The ECB plays a central role in the establishment of theNew EU Chemicals policy. It is responsible for the tech-nical and scientific work needed for the development,introduction, and adaptation to technical progress oftesting methods of Annex V to Directive 67/548/EEC.

The web page for Biocides, http://ecb.jrc.it/biocides,has continuously been updated, to enable industry tocheck that their information is registered correctly andto distribute information to third parties.

The ECB has been engaged in two research activities in2002:

• The OMNIITOX project (Operational Models aNd Infor-mation tools for Industrial applications of eco/TOXi-cological impact assessments) aiming at the en-hancement of the capability of industry to selectmore environmentally benign chemicals and pro-cesses. The main activity in 2002 has been an LCAcase study, comparing application of metal workingfluids with and without chlorinated paraffins.

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Scientific Highlights in 2002

• The promotion of the development, validation andimplementation of (Q)SARs, (quantitative) structure-activity relationships, which will be useful for regula-tory purposes, in particular on the needs of the futureEU legislation on chemicals (REACH system). Thework is performed in close collaboration with ECVAM.

Physical and Chemical Exposure (PCE)

In order to overcome the methodological and data defi-ciencies on human exposure, which represent a majorbottleneck in the risk assessment analysis, the Physicaland Chemical Exposure Unit of the IHCP is developingmethods for improving the characterisation of humanexposure to chemicals and physical stressors. The Unitwas created in June 2002 after the transfer of some se-lected activities from IES to the IHCP.

The UNIE Project (UV-radiation, Noise, Indoor Expo-sure, Electromagnetic Fields) investigates the healthrisk of European citizens from the exposure to environ-mental stressors, including chemicals, biological con-taminants, UV-radiation and electromagnetic fields.

The UV laboratory provides support to specific policyactions on UV and hosts the European Reference Centrefor UV Radiation Measurements (ECUV). In the contextof the HARMONOISE project (“Harmonised, Accurateand Reliable Methods for the EU Directive on the As-sessment and Management of Environmental Noise”)the first measurement campaign to collect noise & mi-crometeorological data, needed for the validation ofthe harmonised model under development, was suc-cessfully performed in 2002.

In the frame of the project PICADA the photo-catalyticactivity of TiO2, added to different building materials(concrete etc.) has been tested for its ability to inducedegradation of inorganic (NO, NO2, O3) and organiccompounds (VOCs) using the INDOORTRON facility.

With the participation of DG SANCO two main projects(EIS-CHEMRISKS and CHEM-TEST) have been formulatedand approved as European-wide networks to systemati-cally exchange and assess information on emergingissues related to “Risks from chemicals released fromconsumer products and articles”.

The Unit has promoted a European Information Systemon public health protection issues related to Electro-magnetic fields (EIS-EMF) as a common basis for deci-sion makers to increase the coherence of the approach-es taken in the various Member States and help restorepublic confidence. In December 2002 the kick-off meet-ing of the project INDEX (Indoor Exposure Limits) wasorganised. The aim of the project is to create a networkof European leading scientists in the area of indoor airpollution and the herewith associated health impacts

in order to identify priorities and assess the need for aCommunity strategy and action plan for the establish-ment of indoor exposure limits for priority pollutants.The INDEX project is financially supported by DG SANCO.

The activities in the area of toxicology focused on thedevelopment of toxicogenomic approach in assessingthe exposure to environmental chemicals and chemicalmixtures. Studies were carried out applying DNA micro-arrays techniques to assess gene expression modulationfollowing exposure to chemical stressors.

Activities in 2002 of the contact materials laboratoriesincluded pre-normative research (migration into dryfoods, active packaging, reaction products from jarsealants, release of chemicals from toys) and monitor-ing of contaminants (from toys and in baby foods). Twolarge conferences on recyclability and on scientific mo-bility and one course of mathematic modeling were or-ganized. The activities in 2002 have resulted in twomilestones: the designation of the contact materialslaboratories as a future Community Reference Laborato-ry by DG SANCO, endorsed by the request of MemberStates to lead and co-ordinate an Official Network ofEnforcement Laboratories. Another milestone has beenthe procedure of accreditation of the laboratory, whichhas resulted in an ISO 17025 Accreditation in January2003.

The institutional work of BEVABS included aspects re-garding training within the frame of the new official la-boratories and quality control of isotopic measurementsfor wines. A new competitive project WINE-DB invol-ving the network of laboratories of the EU Wine Databank, and new partners from candidate countries (Hun-gary, Czech Republic, Croatia and Romania) started inMay 2002.

Biomedical Materials and Systems (BMS)

The Biomedical Materials and System (BMS) Unit deve-lops, validates and uses advanced processing techni-ques and test methodologies for the qualification ofbiocompatible materials, medical devices, and diagno-stic systems including medical applications of nucleartechnology.

The research activities in 2002 in the BMS Unit wereexecuted in two institutional projects, “Reliability ofMedical Devices (REMED)” and “Minimally InvasiveMedical Systems (MIMES)”, focussing on the followingkey areas:

• Surface technology for hybrid bio-interfaces and sur-face analysis for contamination of medical devices.

• Release assessment of biomedical and orthopaedicimplants including performance testing of hip andknee implants.

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• Biomechanical characterisation of calcified tissuesand interfaces.

• Optical and nuclear imaging techniques for cancerdiagnosis.

In the area of surface technology, the aim of the R&Dprogram is to develop, assess and test plasma surfacetreatment for biomedical applications. In particular,progress has been made in the deposition of carbon-based materials for prosthetic applications and on thefunctionalisation of surfaces to improve properties suchas adhesive bonding, wettability and biocompatibility.Another focus of research in 2002 was on the applica-tions of plasma sources for the sterilization of medicaldevices using plasma processes for the destruction ofspores and pyrogens in medical devices and polymertreatment for pharmaceutical packaging.

The set-up of the laboratory for testing of orthopaedicimplants has been completed with a new hip and kneesimulator which complements the existing equipmentfor wear release testing. The laboratory covers the who-le range of testing facilities from screening tests tomost advanced tests simulating the mechanical loadingunder actual conditions.

In the area of optical imaging, work has continued onthe development of endoscopic fluorescence basedmethods for tissue characterisation, while further pro-gress has been made in the development of optical fibrebased sensors for monitoring temperature profiles overextended areas for application in the treatment of tu-mours.

In 2002 the contract for the joint ECVAM-BMS Unit Ma-rie Curie Training Site “Research Training in Biomate-rials Testing Using Radiotracers” (BIORAD) have beensigned and first students have been selected. BIORADaims at providing high-level interdisciplinary doctoraltraining in testing of biomaterials using radiotracers. Akey facility for this Training Site is the IHCP Biocyclo-tron, which is a concept that includes an interdiscipli-nary team of scientists working in an infrastructure of acyclotron, laboratories for both the safe handling of ra-dioisotopes and their use in biological and toxicologi-cal studies.

The BMS Unit manages two Thematic Networks and par-ticipates in six Shared Cost Actions.

Support to Pharmaceutical Research (SPR)

The SPR Unit has developed several complementary in-formation and communication systems aiming at assi-sting the access to the authorised information on medi-cinal products throughout the EU regulatory authorities.In particular:

• The EudraNet Services supporting the cooperation forthe entire EU market and post marketing surveillan-ce.

• The EudraTrack System supporting the marketing au-thorisation process of medicinal products throughthe mutual recognition procedure enforced by theCouncil Regulation (EEC) No. 2309/93 and by Directi-ve 2001/82/EC and Directive 2001/83/EC.

During 2002 the SPR Unit successfully finalized thetransfer of the EudraNet Services to the EMEA and theservices of the EudraTrack System to the BfArM (Bunde-sinstitut für Arzneimittel und Medizinprodukte) regula-tory authority.

The Head of the SPR Unit F. Argentesi retired on 31 July2002. The SPR Unit ceased to exist at the end of 2002.

HUMAN RESOURCES

This section distinguishes the IHCP staff into statutoryand collaborative staff (trainees, PhD and Post Doc grantholders, visiting scientists, national experts):

Statutory staff distribution–2002

The DG JRC employs a total of 1,642 officials and tem-porary agents. Including auxiliary agents the total staffnumber was 1,939. In addition to its core staff, theJRC also hosted a total of 294 grant holders, visitingscientists, seconded national experts and trainees com-ing from the Member States, Candidate Countries orelsewhere (Figures December 2002). Out of the totalJRC staff, IHCP employs 186 statutory staff (includingofficials, temporary agents, and auxiliary agents), andwithout auxiliary agents a total of 158 staff members:

Out of the total IHCP statutory staff (without auxiliaryagents) 41% is scientific staff, 46% is technical staff,and 13% provides management and support. The IHCPscientific staff counts on significant expertise in a widerange of disciplines, such as Analytical Chemistry, Biol-ogy, Biometrics, Biophysics, Engineering, Food chemis-try, Information technology, Science, Medicine, Phar-macology, Physics, Radiochemistry and Toxicology.

Collaborative Staff with Member Statesand Third Countries

The IHCP hosts a large number of collaborative staff(trainees, grant-holders, visiting scientists, secondednational experts) in order to adjust to its research ac-tivities. More specifically, the IHCP hosted 106 collab-orative staff in 2002:

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Management& Support

IHCP Statutory Staff (December 2002) M F Total

Officials 53 21 74

Temporary Agents on 5-year renewable contracts 45 36 81

Temporary Agents on 3-year non-renewable contracts 2 1 3

Total IHCP (without auxiliary agents) 100 58 158

Auxiliary Agents on 1-year non-renewable contracts 11 17 28

Total IHCP (with 30 auxiliary agents) 111 75 186

IHCP Collaborative Staff (December 2002) M F Total

Trainees 17 17 34

Post-Graduate grant-holders 8 26 34

Post-Doc grant-holders 9 13 22

Visiting scientists 5 5 10

Seconded National experts 5 1 6

Total 44 62 106

The IHCP in Figures–2002

41%Scientific

staff

46%Technical

staff

13%

IHCP Statutory staff(without auxiliary agents)–2002

Competitive activities

The advantages of participating in competitive activ-ities are that IHCP gains access to new expertise, andshares its own competencies and facilities. Competitiveactivities also provide another source of income besidesthe institutional budget. In accordance with JRC’s ownregulations, competitive projects must complement theJRC’s mission and must respect the subsidiarity princi-ple.

There are three types of competitive activities:

• Participation in shared-cost activities (SCA) with othersuccessful consortia.

• Activities financed in the context of other EU policies(non-research) upon request of other Commissionservices (OCA).

• Work undertaken for third parties on a contractual ba-sis (TPW).

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BUDGET

The EU Framework Programmes (FP) for Research andDevelopment set out the general research priorities ofthe European Union in accordance with Article 169 ofthe EU Treaty. A total budget of € 14,940 million wasallocated to the Fifth Framework Programme – FP5(1998-2002). The JRC (seven Institutes) received anamount of € 1,020 million (7%) out of the total FP5budget. The IHCP has been attributed an amount ofaround € 135 million for the period of 1999-2002(around € 33 million annually).

In general, IHCP credits come from the institutionalbudget (made available directly from the aforemen-tioned European budget to the JRC); competitive activ-ities; and associated states.

Institutional activities

The JRC defines its broad research areas into its multian-nual JRC Work Programme (1999-2002). The JRC WorkProgramme is updated annually (annual Work Pro-grammes), and where appropriate, adaptations are madefollowing exchanges with “customer” Directorate Gener-als to review progress and consider new needs. The 2002JRC Work Programme is arranged according to the follow-ing programme lines: a) safety of food and chemicals, b)environment, c) dependability of Information Systemsand Services, and d) nuclear safety and safeguards.

The majority of the IHCP projects contribute to the‘Safety of food and chemicals’ programme line. Theavailable credits to IHCP are divided into staff expens-es, means of execution (maintenance of buildings andequipment, electricity, insurance, consumables, etc.)and operational credits (scientific acquisitions). Thefollowing table presents the IHCP institutional budgetbased on its projects in 2002:

IHCP Institutional Budget 2002–Institutional Projects (K€)

INSTITUTIONAL PROJECTStaff Means of Operational

Totalexpenses execution Appropriations

Safety of food and Chemicals, and health related issues

FPU Control of Quality & Safety of Food & Related Items 2,616 90 660 3,366

FPU/ Support to the Implementation of Community PolicyGMO on biotechnology (GMO)

3,240 130 660 4,030

ECVAM Validation of alternative methods (ECVAM) 4,810 110 1,700 6,620

ECB Chemical products, environment risk assessment (ECB) 6,319 80 865 7,264

BMS Reliability of Biomedical Devices (REMED) 4,739 50 300 5,089

BMS Minimally Invasive Medical Systems (MIMES) 2,071 20 100 2,191

Environmental-Enhancing Sustainability

PCE UV-Radiation, Noice, Indoor Exposure,Electromagnetic Fields (UNIE)

5.067 110 250 5,427

Dependability of Information Systems and services

SPR Telematic system for the EU pharmaceuticalregulatory activity (ETOMEP)

1.752 35 260 2,047

Total 30,614 625 4,795 36,034

In 2002, the IHCP had 21 ongoing Shared Cost Actions.Most of the projects fall under the “Competitive andSustainable Growth” programme while the remainderfall under the “Quality of Life” Programme. Moreover,

the IHCP had one ‘other competitive activity’ (OCA) onnetwork services for the pharmaceutical regulatory sec-tor.

1. The B&GMO unit was part of the FPU until June 2002. The FPU was

transferred from the IHCP (Ispra) to IRMM (Geel, Belgium) during

the summer of 2002. B&GMO was officially established in November

2002. G. van den Eede was appointed as Head of Unit on 1st April

2003.

2. M. Balls served as unit head of ECVAM until June 2002. Following

his retirement on 1st July 2002, T. Hartung was appointed as Head

of Unit on 1st October 2002.

3. The PCE unit was created in June 2002 after the transfer of some

selected activities from the Institute for Environment and Sustain-

ability (IES) to the IHCP.

4. F. Argentesi retired on 31st July 2002. The SPR unit ceased to exist

at the end of 2002.

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IHCP Organisational Chart

DirectorK. Van Leeuwen

Management SupportB. De Bernardi

Biotechnologyand GMOs1

G. Van den Eede

European Centrefor the Validation ofAlternative Methods2

T. Hartung

EuropeanChemicalsBureau

G. Vollmer

Physical andChemical Exposure3

D. Kotzias

BiomedicalMaterials and

SystemsH. Stamm

Support toPharmaceutical

Research4

F. Argentesi

Income from Competitive Activities (K€)

Type K€ %

Shared Cost Actions (SCA) 1,090 45

Other Competitive Activities (OCA) 1,027 42

Third Party Work (TPW) 307 13

Total 2,424 100

Institutional ProjectSupport to the Implementation

of the Community Policy on biotechnology and GMOs

Some Shared Cost ActionsQPCRGMOFOOD, ENTRANSFOOD

Biotechnology and GMOs

Web information resourceshttp://biotech.jrc.it/

http://engl.jrc.ithttp://gmoinfo.jrc.it

m&bg os

m&bg os

In recent years many genetically modified organisms orproducts derived thereof have been marketed world-wide, mostly for food or feed applications. The EU hasadopted a number of regulatory acts to safeguard thehuman and animal health, to protect the environmentand to provide freedom of choice for consumers.

IHCP work in this area is focussed on the developmentand validation of appropriate methods for detection,identification and quantification of Genetically Modi-fied Organisms (GMOs) in different types of matrices.The European Network of GMO Laboratories (ENGL) thatit runs with national control laboratories is seen world-wide as a network of scientific reference. In addition,the Unit has expertise in environmental risk assess-ment, in bioinformatics and in issues related to sam-pling. The Unit works closely with the JRC’s Institutefor Reference Materials and Measurements (IRMM), re-sponsible for the production of GMO reference materialsand with the JRC’s Institute for Prospective TechnologyStudies (IPTS) on the elaboration of topical studies.

The Biotechnology & GMOs Unit is the JRC reference forthe provision of scientific and technical support to theEC biotechnology regulatory framework and to developbiotechnology expertise in areas relevant for healthand consumer protection. It is the youngest of all JRCUnits, created on November 1st 2002 as an offspring ofthe Food Products Unit. The flagship of its activities isthe European Network of GMO Laboratories (ENGL) thathas been inaugurated in December 2002 as a result of acollaboration between more than 40 control laborato-ries under the chairmanship of IHCP. Alongside theseactivities, and in support to ENGL, a number of activi-ties deal with (bio)informatics, with molecular biologyresearch, with method development and validation, andwith data mining and sampling. A great deal of atten-tion has also been spent on the development of train-ing courses in collaboration with WHO.

The Unit mostly, but not exclusively, collaborates withDG SANCO and DG ENV. Intensive programmes have alsobeen set up with enlargement countries. In addition,excellent contacts have been established with interna-tional research organisations as well as with the bio-technology industry.

THE EUROPEAN NETWORKOF GMO LABORATORIES (ENGL)

The European Network of GMO Laboratories (ENGL) isset up to contribute more effectively to the Europeanharmonisation and standardisation of means and meth-ods for sampling, detection, identification and quanti-fication of GMOs or derived products in a wide variety ofmatrices, covering seed, grains, food, feed and environ-mental samples. As such, it is aimed to act as a scientif-ic and technical European Union network of excellencewithin the context of EU GMO regulation. Projects of ex-cellence and innovation and rapid exchange of datawithin its members are key issues of ENGL.

Putting in place ENGL is done with the intention to es-tablish a European system for scientific reference forthe purpose of:

• Enhancing pan-European harmonisation and stand-ardisation of GMO sampling and analysis.

• Aiding the effective application of such proceduresthrough encouraging the preparation of referencematerials and the participation in proficiency testingschemes.

The scope is to create a unique platform for expertswhere technical items can be put forward and dis-cussed, namely:

• Method development for qualitative and quantitativeanalysis.

• Molecular biology technology transfer.• Validation and proficiency studies of methods suita-

ble either for screening of various matrices for thepresence of GMOs, or for the estimation of the GMOquantities present.

• Reference material (the responsibility for this workpackage lies with the JRC's Institute for ReferenceMaterials and Measurements).

• Sampling strategies and procedures for different GM-commodities (seeds, grains, raw material, productsfor final consumer or mass caterers).

• Databases and bioinformatics and requirements forunique identification of GMOs and setting up of data-bases that contain these molecular data.

A restricted Web site, the "Bulletin Board of the Europe-an Network of GMO Laboratories", has been set up withthe purpose to facilitate exchange of information, postnotices and view information on news and events.

The network currently consists of 44 EU enforce-ment laboratories, plus Norway and a number of observ-ers such as representatives from Accession Countries.

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Biotechnology and GMOs (B&GMOs)

The chairmanship is under the responsibility of the Bio-technology and GMOs Unit.

Although four plenary sessions and a number of work-ing group sessions had already been held, the networkwas officially inaugurated in Brussels on December 4th

2002 in the presence of Commissioner Busquin, JRC Di-rector General, Barry Mc Sweeney and IHCP DirectorKees Van Leeuwen.

The event received impressive press coverage: over 35publications have been issued worldwide in prestigiousnewspapers and journals such as Nature, Science andThe Lancet.

On the same day, stakeholders’ meeting was organisedto which about 200 participants took part. The meetingwas chaired by Prof. W. Moens (Institute for Hygieneand Epidemiology, Belgium ) and the following itemshave been covered:

• Overview of GM-legislation, with a particular empha-sis on the needs for technical and analytical supportHeidi Hoffmann, Ministry of Federal and European Af-fairs of North Rhine-Westphalia (Germany).

• Sampling large lots for GMO contamination: what canbe reasonably achieved?Claudia Paoletti, DG Joint Research Centre - IHCP, Is-pra (Italy).

• Detection, identifications and quantification of GMOsand derived products: present and future challenges.Arne Holst Jensen, National Veterinary Institute Oslo(Norway).

• Method validation: what can be realisticallyachieved?Hermann Broll, Bundesinstitut für gesundheitlichenVerbraucherschutz und Veterinärmedizin (BgVV) Ber-lin (Germany).

• Value and applicability of a validated method forcontrol purposes.Roger Wood, Food Standards Agency London (UK)

• Past and future of reference materials.Heinz Schimmel, DG Joint Research Centre - IRMM,Geel (Belgium).

• The role of the European Network of GMO LaboratoriesGuy Van den Eede, DG Joint Research Centre - IHCP,Ispra (Italy).

BIOINFORMATICS AND DATABASES

Efforts on building a bioinformatics expertise havebeen mainly focussed on pursuing the development ofan ENGL Molecular Register and on the follow-up ac-tions of a brainstorming meeting on a Reference Aller-gen Register.

ENGL Molecular Register

The ENGL Molecular Register, with the ENGL and theB&GMOs Unit as its primary customers, mainly providesaccess to a GMO events database and to relevant analy-sis tools. One of the strengths of the development teamlies within the diversity of the profiles: the register hasbeen compiled with input from competent authorities,from bioinformatics experts and from computer scien-tists.

The development of the Molecular Register has beencompleted; it has been installed in the unit and it iscurrently being tested intensively.

Reference Allergen Register

One of the conclusions of an Allergen Database Brain-storming meeting held in 2001 was the need to identifythe current state of the art of publicly available aller-gens database and associated bioinformatics tools.Therefore a review, involving several international part-ners, has been conducted that has led to two articlesproposed for publication.

In addition and to complement the activity on the reg-ister itself, the Unit has decided to embark in the IN-FORMALL concerted action project aimed at developingcommunication strategies in the food allergy area, topromote the provision of visible, credible sources of in-formation appropriate to different stakeholders includ-ing consumers, industry and regulators. The projectkick-off is planned for 2003 and should last 3 years.

DATABASES AND INFORMATION TO COMPETENTAUTHORITIES AND TO THE GENERAL PUBLIC

Both the environmental legislation and the GMOfood/feed legislation have evolved significantly in2002. October 17th was a particularly important datebecause from then on the new Directive (2001/018/EC)came into force. There are a large number of provisionsdealing with exchange of communications between au-thorities, the European Commission and the public.

DG Environment and Member States’ Competent Author-ities (CA) have mandated the JRC since many years toprovide electronic means for the exchange of informa-tion on the GMO Notifications Summary, including con-fidential data, if compliant with confidentiality rules.

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Web technology enables all users (Applicants, MemberStates’ Competent Authorities, and European Commis-sion) to retrieve the appropriate amount of informationby granting the appropriate level of access and securityto each user. Therefore, the Unit has developed a web-based system to facilitate the circulation of informa-tion between the Competent Authorities and the Euro-pean Commission.

The system has two different functions: to grant com-petent authorities access to an Intranet-based Webinterface to enter data on field trials in a user-friendlymanner and secondly, once completed, to providethe general public access to an open Internet-sitehttp: //gmoinfo.jrc.it. On December 18th the Biotech-nology&GMO Unit has trained all competent authoritieson how to use the new system.

VALIDATION STUDIES, DATA MINING,SAMPLING STRATEGIES AND TECHNOLOGY TRANSFER

There are a number of EU regulatory acts that lay downthe requirement for analytical control for compliancewith labelling regulation. For instance, during 2002Member States were recommended to carry out inspec-tions and controls (2002/66/EC) including taking sam-ples and analysing such samples in laboratories withthe aim of monitoring compliance with such Communi-ty rules on labelling. Therefore, much of the validationwork of the B&GMOs Unit should be looked at in thiscontext, as well as in the light of the operation of theEuropean Network GMO laboratories.

Database on validated methods

The enforcement laboratories must evaluate the methodperformance in order to select the most appropriatemethod and, subsequently, must apply the analyticalmethods that suits best for a certain purpose. To allowthis, a database containing a range of information onvalidated methods for GMO analysis has been compiled.

The direct and user-friendly access is available on-line(http://biotech.jrc.it/), and the database currentlycontains information about 220 validated methodsfrom all over the world. The data reported in this data-base have been published in peer review journals or inreports from collaborative studies that are available inthe public domain. There is general information on theGMO and its application possibilities, informationabout the method performance as well as essentialtechnical information about the method (i.e., primersequences, amplicon length, apparatus, control primersequences, use of certified reference materials, methodof amplicon verification etc).

DG SANCO has requested the IHCP whether the informa-tion on methods for detection and identification ofGMOs reported by CODEX Alimentarius member coun-tries could be hosted on the above database. This workis currently going on.

Validation Studies & Data Mining

During 2002 the majority of the validation studies werecarried out within the shared cost action project QPCRG-MOFOOD (see below). In addition, the first validationprocesses for regulatory compliance (in support to theimplementation of Regulation 258/97 on novel foods) incollaboration with large industrial companies were initi-ated. The validation process is a true team effort inwhich constant performance is required from the methoddevelopment and co-ordination of the study through thering trial participation up to the data analysis and evalu-ation. During 2002, we have up-graded all our proce-dures related to the validation in order to carry out thering trials according to the highest internationalstandards, and to collaborate intensively with the ENGL.About 100 laboratories from the Pan-European area ex-pressed their interest to participate in these ring-trials.

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Sampling Strategies

The schemes adopted for the sampling of food productslots are of crucial importance to ensure accuracy andprecision of GM testing surveys. One of the priorities ofthe B&GMOs Unit is to identify and develop appropriatesampling strategies to support EU legislation for thedetection and quantification of GMOs in different mar-ket products.

According to current routine sampling procedures forkernel lots analysis, GM material is assumed to be ran-domly distributed, so that the producer and consumer’srisk can easily be estimated according to the binomialdistribution. However, the assumption of random distri-bution of GM material in kernel lots is likely to bewrong. Indeed, it must be taken into account that in-dustrial activities are well framed in time and space.This generates correlations that, ultimately, will pro-mote segregation during transportation and handlingof the material. Our objective is to assess the effect ofheterogeneity on the detection of low levels of kerneltraits, such as GM material, in large grain or seed lots. The activity of the B&GMOs Unit in this field encom-passes three different aspects:

1. Theoretical-statistical work• Research and development of sampling methods for

the detection and quantification of GM materials indifferent market products.

• Technical evaluation of the available or newly devel-oped sampling plans for GMO detection / quantifica-tion with particularly respect to their statistical as-sumptions and implications.The Unit has developed and published a new ap-proach to investigate the effects of different levels ofheterogeneity on the accuracy and suitability of dif-ferent sampling plans for the detection of GM parti-cles within kernel lots. The flexibility of the proposedmodel allows the simulation of a large number of ker-nel lots, with defined population characteristics,without imposing any constraint on the distributionof GM kernels. The results of the Unit show that cur-rent procedures for the procurement of kernel sam-ples, as stipulated in international guidelines, aresensitive to non-uniform distribution of impurities.In cases of heterogeneous GM material distribution,the samples have a high probability of not correctlyrepresenting the lot and/or even not containing anykernels with the trait under investigation (false-negative results). The tools developed by the Unit toevaluate sampling schemes for the detection of GMmaterial in large kernel lots may also be applied topurity testing for other types of kernel traits. Theseresults issue a clear warning with respect to the un-conditional acceptance of standardized sampling pro-cedures in absence of the knowledge of GM materialdistribution in kernel lots.

2. Development of new software (Kernel Sampling Tech-nique Evaluation – KeSTE) to assess the suitability ofdifferent sampling protocols as function of lots prop-erties. First, the program allows creating populations.Second, the population developed can be sampled us-ing either a random or a systematic sampling scheme. The user can specify a range of increments (samples)and a range of sample sizes (kernels no. per sample).Response surfaces are built to identify proper sam-pling techniques.

3. Co-ordination of the EU pan-project KeLDA (KernelLot Distribution Assessment). This collaboration be-tween ENGL, IRMM and the B&GMOs Unit representsthe first study ever carried out to assess the real dis-tribution of GM materials in grain lots imported with-in EU Member States. The JRC is participating withthe B&GMOs Unit and the IRMM in Geel. The projectstarted in May 2002 and is successfully continuing.Molecular methods proposed to the participants forthe analysis of the KeLDA samples were revised andtested in the molecular biology laboratory of the unitto assess their performances in terms of sensitivityand specificity. The methods are the same the labora-tories involved in the project have to use to analysethe increments sampled. Methods include PCR detec-tion of soybean housekeeping gene (lectin) andscreening for p35S promoter in soybean. Referencematerials were used at GM levels of 2%, 1%, 0.5%,0.1% and 0%. In addition to the DNA-based detec-tion methods, a protein-based approach for the de-tection of RoundupReady (RUR) soybean has been in-cluded. The method makes use of the Lateral FlowTest Strips (SDI Inc.), an easy to perform and quickapproach for the determination of the presence ofRUR soybean in test samples. It could be demonstrat-ed that, when proper conditions are applied (properparticle size, dilution of the test sample, incubationtime), the LOD (Limit of Detection) of the system isat least 0.033%, which means that the test is capableto detect the presence of 1 particle in 3000. No falsepositives were detected at the tested conditions. Theactivity was carried out in collaboration and in sup-port of IRMM, where the strip tests on samples areperformed using the protocol developed.

MOLECULAR BIOLOGY LABORATORY

Method, development and optimisation

The principal aim and objective of the Molecular Biolo-gy Laboratory of the Biotechnology & GMOs Unit is toperform high quality research for the identification, op-timisation and validation of suitable and efficient DNA-based and protein-based analytical methods for thedetection and quantification of genetically modified or-ganisms – in raw materials, ingredients and final pro-ducts – in support to current EU legislation.

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Another objective relates to ensuring that the laborato-ry is at the leading edge of GMO detection technologyby exploring and exploiting suitable promising opportu-nities, to anticipate analytical needs and to be preparedto propose solutions and methodological alternatives.

In this context, the projects and activities carried outin the method optimisation and method developmentlaboratory during the reported period are briefly sum-marised and described hereafter.

Development and optimisation of multiplex real-timepolymerase chain reaction (PCR) based system for thequantification of the CaMV 35S promoter in maize lines.

The aim of the project is to have one unique and there-fore convenient quantitative screening system to as-sess the GMO content in all GMO maize lines currentlyplaced on the market in Europe. After optimisation interms of primers and probes concentration, DNA extrac-tion and DNA concentration, a full characterisation ofthe method has been carried out, and performance cri-teria have been evaluated in an in-house validation.

The real-time PCR method developed and optimised forMON810 for a reliable estimation of the GM content hasbeen applied for the study of the effect of gene copynumber in different GM events on the accuracy of GMquantification.

For such a study, amplification reactions have been car-ried out on the following DNA of GM maize lines ap-proved in Europe: MON810 (DNA extracted from leafmaterial), Bt-176 (DNA extracted from leaf material andDNA extracted from Certified Reference Material), Bt-11and T25 (DNA extracted from leaf material). As an out-come of the project, the real-time quantitative methodcan be applied for accurate quantification of MON810,Bt-11 and Bt-176 CRM materials. For commercial varie-ties, due the uncertainty on their genetic composition,the method can be reliably applied provided that thegenetic composition is known which is subject of thestudy described below.

Study of the copy number of the maize reference geneszein, invertase, hmg and adh in 30 different GMO and wtmaize lines.

The relative poor characterisation of the variability ofthe copy number of the most employed maize referencegenes causes several problems in the precise quantifi-cation of GMOs. In fact, it is possible that different hy-brids of the same GMO at the same relative concentra-tion give different quantifications as a consequence ofthe different copy number of the used reference gene.The study uses a plasmid containing real-time PCR tar-gets specific for the four reference genes at the 1:1:1:1ratio and several maize lines belonging to almost allbreeding groups currently used world-wide.

Development and optimisation of multiplexed real-timePCR quantification systems using novel probe systems(MGB – minor groove binding) recently placed on themarket.

The aim of this project is to assess and compare the ef-ficiency of the novel probe design (MGB) with respectto the traditional Taqman degradation probes. A multi-plexed method for the quantification of the Round-upReady soybean has been chosen as a model and itsoptimisation is underway.

Development of novel plasmid based reference materialsfor the quantification of GMOs.

Plasmids are convenient substitutes of the currentlyused Certified Reference Materials (CRMs) produced bythe IRMM. Two different approaches are under investi-gation: the first approach uses co-clones of the GMOspecific sequences and the reference gene in one singleplasmid to plot a serial dilution based standard curvewith a high dynamic range. The fixed 1:1 ratio ensuresthe precision of the quantification. The second ap-proach is based on blending two plasmids at given con-centrations producing materials similar to the IRMMCRMs.

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Serial dilution based standard curve with a high dynamic range

Serial dilution based standard curve with a high dynamic range.

Proficiency Testing (PT)

Proficiency Testing (PT) is a quality tool that measuresthe outputs of a laboratory. PT is complementary toother quality tools that are concerned with inputs suchas use of CRMs, implementation of a formal quality sys-tem, etc.

The aim of the PT activity of the Biotechnology andGMOs Unit is to establish an internal quality tool, whichmonitors, over time, the analytical performance of thelaboratory in GMO testing.

The PT schemes to which the laboratory has participat-ed in the period covered by this report are:• Fapas – GeMMa (Central Science Lab. – York) Food

Analysis Performance Assessment Scheme - 6 Rounds• Progetto Trieste (Tecna Trieste) – 2 Rounds• IFR (Institute of Food Research – Norwich UK) – 1

Round• USDA – GIPSA (Grain Inspection Packers and Stock-

yards Administration) – 3 Rounds The table below summarises the types of samples thathave been analysed during PT activity.

Over 700 analyses have been carried out for GMOscreening and identification as well as quantification. Abroad range of analytical techniques has been em-ployed including PCR, nested PCR, semi-nested PCR, Re-al-Time PCR and immunoassay tests (ELISA).

In the period covered by this report, qualitative andquantitative analyses requested by Schemes GeMMAand GIPSA have been carried out. In particular, a proto-col for the detection of maize CBH351 (Starlink) andRoundup Ready corn GA21 has been employed withpositive results in addition to the routinely event-specific tests used (for the identification of Roundu-pReady soybean, maize Bt-176, Bt-11, MON810, T25).

Collaboration with IRMMfor the certification of CRMs

The replacement material of Bt-176 maize was shippedto the IHCP by IRMM for pre-marketing testing on ho-mogeneity and precision of percentage GM levels. Sam-ples were extracted and tested on Real-Time PCR usinga 35S-based quantitative method validated internally.Results showed accuracy of quantification and wereprovided to IRMM as support to the certification proc-ess of the new series of Bt-176 CRM.

Genomics Project

One of the environmental concerns of transgenic cropsis about the stability of the transgene constructs. Lit-tle is known about what happens with a transgene con-struct once it is introduced into the plant genome. Newvarieties are carried over during several plant crossesand undergo different environmental conditions andstresses. On the other hand, detection methods for GMconstructs in plants or involving plant specific se-quences (the integration site of the insert) need to re-main effective and reliable regardless the treatment ofthe plant, its growth in space or over time. Therefore, itis important to understand how stable the inserts areover time and under several physiological and ecologi-cal conditions.

A project addressing the issue of stability was startedin collaboration with the CLO in Gent, Belgium, andplant material was provided by the VIB/RUG, Gent.

A part of the project consists of characterising thetransgene construct in some transgene crops. Anotherpart concerns a study of stability of the transgene inthe model plant Arabidopsis thaliana. This plant hasseveral advantages such as easy growth, quick growingcycle, small genome, a variety of tools applicable and afully sequenced genome and hence it is successfullyused in plant science. Currently, a collection of Arabi-dopsis thaliana T-DNA insertion lines is being analysedfor location of the insert in the genome and studied forstability (re-arrangements, deletions, insertions, singlenucleotide polymorphisms) of the flanking regions ofthe transgene construct. A similar analysis will be car-ried out for the wild-type line. Comparisons can bemade between the pre-insertion site and the insertedsite of the genome. The methods that are used in theB&GMOs Unit include anchor PCR, fragment sizing, sin-gle strand conformation polymorphism (SSCP) and DNAsequence analysis. As the screening of several thou-sands of plants is foreseen, a high-throughput systemis currently being tested using either radioactive label-ling combined with gel-electrophoresis or fluorescentlabelling with capillary gel-electrophoresis.

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Raw materials Processed materials

Soya flour Baked soybean cake

Maize flour Baked maize cake

Mixed flour Toasted soybean flour

Wheat flour Soya Lecithin

Tobacco dried leaf Vegetable puree

Soya milk powder

Snack food crumb

Baked biscuit crumbs

Canned meat

Proteomics in Biotechnology and GMO

The aim of this project is to promote and develop asuitable approach to implement protein based analyti-cal methods for the detection of GMO specific proteinsand allergenic proteins in raw materials, ingredientsand final products and to carry out validation studies ofprotein-based methods in support to EU legislation. In2002 a new infrastructure has been set up enabling theperformance of these tasks.

The majority of protein detection methods, currently inuse, are based on specific antigen-antibodies immuno-reactions therefore the research activity is focused on:

• Development of suitable antibodies against proteinallergen.

• Retrieval of commercial GMO antibodies.• Characterisation of target protein with conventional

techniques such as ELISA, mono and two-dimensionalgel electrophoresis, Western blots.

• Application of Luminex technology as innovative ap-proach in GMO and allergenic protein detection.

Training & Capacity Building;relation with the Enlargement Projects

In 2002 two training courses on “The Analysis of FoodSamples for the Presence of Genetically Modified Or-ganisms” have been organised in collaboration with theFood Safety Programme within the European Centre forEnvironment and Health - Rome Division (ECR) of theWorld Health Organisation. The training courses arepart of the collaborations between the two Institutionsto promote food safety related issues in the WHO Euro-pean Region, inside and beyond the actual EU borders,taking into special consideration EU Accession Coun-tries, as well as Central and Eastern Countries with eco-nomies in transition.

The scope of the training courses is to assist the staff ofcontrol laboratories to become accustomed with molec-ular detection techniques, and to help them to adapttheir facilities and work programmes to include analy-ses to comply with world-wide regulatory acts in thefield of biotechnology.

The areas covered during the training courses are:• DNA extraction from raw and processed materials.• Screening of foodstuffs for the presence of GMOs by

simple and nested PCR.• Quantification of GMOs in ingredients by real-time

PCR.• Quantification of GMOs in ingredients by ELISA.

Trainees came this time from Brazil, Croatia, Cuba, Cy-prus, Czech Republic, Estonia, Germany, Greece, HongKong, Hungary, Italy, Lithuania, Poland, Portugal, Ro-

mania, Russia, Slovakia, Slovenia, The Netherlands,United Kingdom, United States and Yugoslavia. In addi-tion, The Agricultural Centre from Gödölö delegated onecollaborator to both training sessions to learn how totrain. A collaboration was initiated for a specific train-ing programme destined to enlargement countries.

Besides the training courses, the Biotechnology & GMOsUnit has offered individual training for specific needs.Training in this topic has been frequently requested dueto its importance according to the increasing need tocomply with current European legislative framework.

Being aware of the need for a permanent source of in-formation the Biotechnology and GMOs Unit staff hascompiled, improved, and edited a Manual, which de-scribes some of the techniques used in its laboratory.

PARTICIPATION IN COLLABORATIVE PROJECTS

QPCRGMOFOOD

The role of the JRC in this shared cost action project,which is is now approaching its end, to co-ordinatework package 5, which deals with the validation of allmethods developed in the other work packages. Meth-ods deal with extraction, event-specific detection andevent-specific quantitation.

The primary objectives are:• Develop reliable and transformation-event-specific

tests for qualitative and quantitative detection of ge-netic modifications in food.

• Develop reliable and transformation-event-specificmultiplex tests for determination of the diversity ofgenetic modifications in food.

• Investigate how improved methods for detection ofgenetically modified foods will influence consumerconfidence in food security and trust in science andrisk regulators.

The B&GMOs Unit is responsible for the designs of thering-trials, the co-ordination and organisation of thestudies, the analysis of the data, the evaluation andcommunication of the results and the supply of recom-

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mendations for the method application. A generalscheme for the validation studies was developed, andon the second half of 2002, reference gene systems formaize, soybean and oilseed rape as well as DNA extrac-tion methods for different maize and soy matrices weretested in multi-laboratory validations. In addition, thepre-validation of nine quantitative GMO-specific meth-ods was launched. The validated methods will be sub-mitted to CEN to become European standards in theGMO testing field.

The molecular biology laboratory activity on prepara-tion and management of validation studies can be sum-marised as follows:• Stock samples receipt from method developer.• Recording and storage of samples and materials.• Samples check and determination of precise DNA con-

centrations.• Preparation of standards and unknowns at the GM lev-

els required.• Real-time amplification and reagents check before

shipping.• Finalisation of operative protocols.

ENTRANSFOOD

The aim of ENTRANSFOOD is to identify proper researchstrategies and tools to address issues related to safetyand management of transgenic food products. Partici-pants discuss new approaches and establish a perma-nent platform for communication between the variousparties involved. As a result various Working Groupswrite a number of research papers and position docu-ments.

The main objectives are:• To identify key issues of the safety evaluation of ge-

netically modified food crops, and to examine wheth-er current research methods are adequate to charac-terise specific safety hazards.

• To design new (in-vitro) test methodologies for safetyand nutritional evaluation of whole complex foods,which are of sufficient sensitivity and specificity.

• To address the risks of gene transfer from geneticallymodified organisms to the bowel microflora of hu-mans and animals.

• To examine new strategies for the detection of genet-ically modified foods, which enable detection at spe-cific threshold levels for raw materials, processedproducts and food ingredients.

• To develop a communication platform of producers ofGMOs, scientists involved in research and safety eval-uation of GMOs, retailers, regulatory authorities andconsumer groups with the scope to improve safety as-sessment procedures, risk management strategies andrisk communication.

The role of the Biotechnology and GMOs Unit is to chairWorking Group 3 on “gene transfer in relation to thesafety of food and feed derived from GM-plants”. TheBiotechnology and GMOs Unit will also involved in theorganisation of the closing meeting, due to take placein Rome on 29 to 30 May 2003.

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SELECTED PUBLICATIONS 2002

ANKLAM, E.; GADANI, F.; HEINZE, P.; PIJNENBURGH, H.; VANDEN EEDE, G. – Analytical Methods for Detection and Determina-tion of Genetically Modified Organisms in Agricultural Crops andPlant-Derived Food Products. European Food Research & Technol-ogy, Vol. 214, (2002) 3-26

ANKLAM, E.; HEINZE, P.; KAY, S.; VAN DEN EEDE, G.L.M.; POP-PING, B. - Validation Studies and Proficiency Testing. Journal ofAOAC International, Vol. 85, No. 3 (2002) 809-815

BONFINI, L.; HEINZE, P.; KAY, S.; VAN DEN EEDE, G. – Review ofGMO Detection and Quantification Techniques – EUR 20384 EN(2002)

BONFINI, L.; KAY, S.; HEINZE, P.; VAN DEN EEDE, G. – Report onGMO Detection, Identification and Quantification Methods Sub-mitted to Collaborative Studies – EUR 20383 EN (2002)

KAY, S. – Report to the 3rd Meeting of the European Network ofGMO Laboratories on the Validation Study of an ELISA Kit for theQuantification of Roundup Ready® Soy Fraction Matrices in Ani-mal Feed Ingredients, April - October 2001 – EUR 20234 EN(2002)

KAY, S.; PAOLETTI, C. – Sampling Strategies for GMO Detectionand/or Quantification – EUR 20239 EN (2002)

PAOLETTI, C.; DONATELLI, M.; KAY, S.; VAN DEN EEDE, G. – Sim-ulating Kernel Lot Sampling: the Effect of Heterogeneity on theDetection of GMO Contamination. Seed Science and Technology –in press

VAN DEN EEDE, G.; KAY, S.; ANKLAM, E.; SCHIMMEL, H. - Analyt-ical Challenges: Bridging the Gap from Regulation to Enforce-ment. Journal of AOAC International, Vol. 85, No. 3 (2002)757-761

PRIZES / AWARDS TO STAFF FOR THEIR ACHIEVEMENTS

Janna Puumalainen, co-ordinator of the data mining and sam-pling project received the JRC Young Scientist Award for Envi-ronmental Research in December 2002 and in addition, she re-ceived an award for the achievements in an international careerby the Faculty of Forestry of the University of Joensuu, Finland,on the 11th of October, 2002.

CONTACTS

The Unit has put a lot of effort to implement a dynamic policyof communication and of public relations. Therefore it is sug-gested to visit regularly each of the three web-sites listed andto have a look, for instance at the Biotechnology and GMOsNewsletter that is regularly published on-line, together with anoverview of all on-going and planned activities, papers pub-lished, training courses and conferences planned.

Head of UnitGuy van den EedeTel.: +39 0332 789755Fax: +39 0332 785483guy.van-den-eede@cec.eu.int

Communications and Public relationsRossella SperoniTel.: +39 0332 785959Fax: +39 0332 785438rossella.speroni@cec.eu.int

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Web information resourcesAt IHCP sitehttp://ihcp.jrc.cec.eu.int/Activities/ACTVali/ACTVali.htmlAt the ECVAM sitehttp://ecvam.jrc.itAt the ECVAM Scientific Information Service sitehttp://ecvam-sis.jrc.it/

Institutional ProjectThe validation of alternative methods

Some Shared Cost ActionComparison and Validation of Novel Pyrogen Testsbased on the Human Fever Reaction

cevamcevamEuropean Centre for the Validationof Alternative Methods

The Validation of Alternative Biomedical Test Methods

The European Centre for the Validation of AlternativeMethods (ECVAM) is an international reference centrefor the development and acceptance of alternative te-sting methods to replace, reduce or refine use of labora-tory animals in the biomedical sciences with emphasison toxicological assessments. ECVAM was establishedby a communication of the European Commission (SEC91/1794) referring to a requirement in the animal pro-tection Directive 86/809/EEC.

ECVAM’s work is focused on the development and evalua-tion of in vitro methods (e.g. cell and tissue cultures),the use of computer modelling based on structure-activity relationships, and on physiological and biokine-tic modelling. ECVAM’s role is to co-ordinate internatio-nal validation studies, to act as a focal point for theexchange of information, to set up and maintain a data-base on alternative methods, and to promote dialogueamong legislators. Moreover, ECVAM plays an active rolein the pre-normative research activities of the JRC.

Due to the political sensitivity of its duties, ECVAM,uniquely at the JRC, has its own Scientific AdvisoryCommittee (ESAC) with participation from all MemberStates, relevant industrial associations, academic toxi-cology, the animal welfare movement, as well as otherCommission services with an interest in the alternativesarea.

Consequently, ECVAM has established a wide internatio-nal network of collaborators in the Member States, andall over the world. ECVAM also works in close collabora-tion with other Commission services, such as DG Envi-ronment, DG Enterprise, DG Research and DG Health andConsumer Protection.

ECVAM and the Chemicals Policy

Serious decisions must be taken on the potential ef-fects of various kinds of chemicals and products to gua-rantee their safe handling and to protect consumers he-alth as the ultimate goal. To this aim, the Commissionissued a White Paper outlining its chemicals policy stra-tegy with the overall aim to provide a uniform regula-tory framework for chemical substances harmonisingtesting requirements for existing and new chemicals.The Council and the European Parliament has asked forECVAM's strong involvement in order to minimise theuse of experimental animals for this purpose and tospeed up the policy implementation throughout the de-velopment and validation of more cost-effective and fa-ster in vitro techniques.

Responding to this request, ECVAM established an ad-hoc Working group on Chemicals with the ultimate goalto propose a strategy on the development and valida-tion of new alternative (non-animal) methods. To bestachieve this objective, ECVAM organised several mee-tings of this working group and its subgroups in 2002,which resulted in the publication of the comprehensivereport "Alternative (non-animal) Methods for ChemicalsTesting: Current Status and Future Prospects" (Editedby Worth, A. & Balls, M. (2002) ATLA, vol.30, suppl. 1). Following the recommendations of the report ECVAMestablished several project management groups for allareas of chemical safety testing and initiated a fund ofthe chemicals industry.

Furthermore, the year 2002 brought news on ECVAM'sleadership. Thomas Hartung from the University of Kon-stanz was appointed as new Head of Unit after the reti-rement of Micael Balls.

The activities of ECVAM can be subdivided into the fol-lowing areas: a) laboratory–based tasks, i.e. areas whe-re ECVAM carries out mainly research and development,b) non-laboratory tasks, i.e. areas, where ECVAM orga-nises (pre)validation studies only c) the ECVAM Scienti-fic Information Service (SIS), and d) other activities.

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European Centre for the Validation of Alternative Methods (ECVAM)

LABORATORY-BASED TASKS

Carcinogenicity and Metal Toxicity

A database on concurrent cytotoxicity and morphologi-cal transformation induced by 30 inorganic and/or or-ganometallic compounds in Balb/3T3 mouse fibroblastswas established. This cell transformation assay is nowavailable for prevalidation. Furthermore, the screeningof the genotoxicity of 20 metal compounds by the hu-man lymphocyte micronucleus assay coupled with fluo-rescence in situ hybrydization (FISH) was carried out.In addition, an evaluation of the genetic damage indu-ced by 15 metal species by using the Comet assay and anew developed protocol employing the human lympho-blastoid cell line (TK6) was completed.

In other areas investigations included screening studieswith the setting of dose-effect relationships for the de-termination of basal cytotoxicity of more than 40 metalcompounds employing different cell lines, as well asstudies on the effects of 25 metal compounds on theimmune system. A comparative study was carried outfor the embryotoxicity and teratogenicity of mercury di-chloride and methyl mercury assayed by the Frog Em-bryo Teratogenesis Assay-Xenopus (FETAX) and a studyon the use of gene expression as a potential molecularbiomarker of early effects of metals.

Furthermore, analytical methods were developed for on-line speciation of chemical forms of arsenic and plati-num in culture media and cytosol of cells by HPLC-ICP-MS, for metabolic studies as key factor for the interpre-tation of the cytotoxic response.

Haematotoxicity and Anti-Cancer Drugs

In vitro haematotoxicology provides the opportunity tostudy the effects of toxicants directly on the relevanthuman target tissues, like bone-marrow and cord bloodcells, reducing toxicological uncertainties due to ani-mal/human extrapolation.

In 2002 a refinement of clonogenic assays for ‘high-throughput' methods has been carried out, comparingdose-response curves and IC50s obtained with the tra-ditional assays and microplate-systems.

Genetic damage to hematopoietic cells may occur in theabsence of any overt hematological sign. The develop-ment of tissue-specific screening systems to detectadverse effects of xenobiotics on target genes is neededfor priority settings of chemicals and drug candidates.The toxicity of various compounds to the human cordblood cells has been evaluated by flow cytometry andconfocal microscopy, as well as macroarray analysis.

Moreover, the ongoing study of the effects of variousp53 mutants on cell growth and apoptosis may help tounderstand the contributions of environmental, occu-pational and recreational exposure to the process ofcarcinogenesis. In this field, the evaluation of the che-mical-induced modulation of apoptosis and cell cycle-related proteins in HepG2 and Hep3B cell lines has beencarried out.

Metabolism, Neurotoxicity and Immunotoxicity

Metabolism is the process by which an administratedchemical is structurally changed in the body by eitherenzymatic or non-enzymatic reactions. Information onthe metabolism of a substance is of crucial importancein the evaluation of toxicological data. Common gene-tic polymorphisms leading to absent, low or increasedactivities in these may influence their toxicological po-tential, and alterations in metabolism may have seriousimplications such as inefficient repair of chemical-induced genetic damage. High-throughput in vitro testmethods were established using genetically engineeredcell lines harbouring polymorphic forms of metabolisingenzymes for studies of polymorphism-mediated effectsafter chemical challenge.

On the other hand, some of these enzymes are induciblein response to foreign compounds, which may result inan increase in toxicity caused by increased formation ofreactive metabolites. As a follow-up of an ECVAMWorkshop and an ECVAM Task Force Report on the appli-cability of hepatocytes in routine testing, an ECVAM in-terlaboratory prevalidation study on the response ofcultured human hepatocytes to model such inducerswas initiated in collaboration with an internationalconsortium.

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Genetically engineerd PC12 neuronal cell line

Up to now, no in vitro methods for evaluating the neu-rotoxic hazard of a chemical have been validated. Thecurrent guidelines from OECD for the Assessment ofNeurotoxic Effects of chemicals are based on in vivostudies. Based on expert advice of a task force and col-laborators, ECVAM established a strategy for the evalua-tion of the neurotoxic potential of chemicals using atiered approach including a battery of mechanistic-based tests, aiming to provide neuropathological, neu-rophysiological and neurochemical information.At present, the toxicological significance of immune re-sponses is under discussion. Immunotoxicity comprisesany effect on the immune system, which might result inincreased susceptibility towards infection or allergy. AtECVAM, a whole blood cytokine release model has beendeveloped to predict the toxicity of foreign compoundstowards the immune system in a simple, fast, economi-cal and reliable way.

Furthermore, the pyrogenicity validation project (5th

Framework Programme Project "Comparison and valida-tion of Novel Pyrogen Tests based on the Human FeverReaction") reached an important stage. Four of the sixcell-based models passed successfully the validationphase.

Molecular Biology and Toxicogenomics

The availability of whole genome DNA sequences andreagents has led to the development of high throu-ghput methods for monitoring expression level of thou-sands of genes simultaneously. Toxicogenomics is a newsubdiscipline derived from a combination of toxicologyand genomics, which allows studying the impact of che-micals and drugs on gene expression. In the past deca-des several in vitro tests have been developed to mea-sure toxicity. Fundamental to all of these methods isthe fact that toxicity is often preceded by and results inalterations of gene expression. In many cases thesechanges in gene expression are far more sensitive, cha-racteristic and measurable endpoints than the toxicityitself.

Toxicants can therefore be identified and their mecha-nisms of action determined by simultaneously analy-zing the toxicant-induced expression pattern. This canbe done by the microarray technology. ECVAM has setup this novel technology, which seems very promisingfor a second generation of alternatives. The aim is touse it in critical key areas where suitable alternativesare lacking, such as carcinogenicity of non-genotoxiccompounds, repetitive dose toxicity or endocrine di-sruptors.

Nephrotoxicity, Barriers and Long-Term Toxicology

In vitro tests are being developed at ECVAM and withcollaborators, for detecting toxicity to various biologi-cal barriers after short and long-term exposure to po-tential toxicants. Since barrier function is an importantdeterminant of absorption and distribution, in vitromodels are developed to assess the passage of chemi-cals across biological barriers, such as the renal barrierand the blood-brain barrier.

The prevalidation study of trans-epithelial resistanceand inulin permeability as endpoints in in vitro nephro-toxicity testing and the study on the evaluation of thereproducibility and transferability of flow cytometryand confocal microscopic endpoints have been finali-sed. ECVAM currently supports the development and re-finement of a Caco-2 cell in vitro model of intestinalbarrier function.

An evaluation of a cell culture medium supplement toreplace the use of animal serum was carried out.

In the context of repeated-dose toxicity, perfusion cellculture systems and other systems available are underevaluation.

Reproductive Toxicology and Cardiotoxicity

In order to reduce the animal consumption for embryo-toxicity testing three methods for in vitro testing havebeen validated during the last years. The results of thedefinite phase and the evaluation of the prediction mo-del have been published and ECVAM’s advisory commit-tee has endorsed the scientific validity of the threemethods. An additional workshop on the practical ap-

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Immunofluorescent staining for tight junctions (green) and nuclei(red) of intact (control) renal LLC-PK1 cells

plication of the methods is planned for 2003 in order toevaluate and promote the application of the threemethods. ECVAM has trained scientists from academiaand industry on one of the validated test.

In addition, ECVAM has continued the project of usingreporter genes for detecting tissue specific effects ofchemicals on the developing embryo. This project hasbeen done in close collaboration with the University ofCologne/Germany. The outcome of the project has ledto the foundation of a Biotech Company in Cologne. Inaddition, the reporter gene technology was employedto establish a system that allows detecting the diffe-rentiation induction of chemicals within four days. In order to discuss the potential of human stem cellsfor in vitro toxicology and therapeutically application aworkshop has been held. The participants formed a con-sortium and submitted an expression of interest to DGRTD on the quality and safety issue of stem cells.

NON-LABORATORY TASKS

Acute and systemic toxicity

In vivo acute systemic toxicity testing is required by re-gulatory bodies to assess the hazard of chemicals, orany other test material, after single exposure, and isusually the first step in a series of toxicological studies.The classical oral LD50 test for assessing the medianlethal dose (LD50, i.e. the dose that kills half the ani-mals in the experimental group) has been deleted fromEU legislation. Three alternative methods have beenadopted, but they are still based on the use of animals.

In 2002 ECVAM started a joint validation study togetherwith ICCVAM (U.S. Interagency Coordinating Committeeon the Validation of Alternative Methods) to evaluatethe relevance of data from two standardised basal cyto-toxicity methods in predicting rodent oral LD50 and hu-man lethal concentrations. The results from this studywill establish to what extent the prediction of oral LD50values can be used to reduce the number of animals inoral acute toxicity testing.

Biologicals

Biologicals are products such as vaccines, immunosera,immunoglobulins, hormones, monoclonal and polyclonalantibodies, which undergo extensive quality control du-ring their production involving often tests on animals.

In 2002 the ESAC endorsed three statements in the areaof biologicals: one on the scientific validity of an ELISAprocedure for the batch potency testing of swine erysi-pela vaccines and two on the deletion of animal testsfor the routine safety testing of veterinary vaccines andfor the batch potency testing of a hormone. A prevali-dation study on the use of PCR for the quality control of

avian vaccines was initiated. A workshop on Three Rsapproaches for the quality control of rabies vaccineswas held and the workshop report will be published in2003. ECVAM participated in the first part of a valida-tion study of an ELISA procedure for the batch potencytesting of Clostridium perfringens vaccines organisedby the German competent authority. ECVAM continuedto submit comments on revision proposals of EuropeanPharmacopoeia monographs in order to promote theThree Rs concept in the quality control of biologicals.

In the field of biologicals ECVAM mainly collaborateswith the competent authorities of the EU Member Sta-tes, the European Pharmacopoeia, industry, and theAdvisory Group on Alternatives to Animal Testing in Im-munobiologicals (AGAATI).

Topical Toxicity and Human Studies

Important progress was made in the field of skin andeye irritation where alternative methods are urgentlyneeded in relation to the EU Chemicals Policy and the7th amendment to the Cosmetics Directive 76/768/EEC.Comments and input on proposals for a 7th amendmentto this Directive were provided through interserviceconsultations.

With regard to skin irritation, the ECVAM Skin IrritationTask Force organised an international validation studyon three in vitro methods: the EPIDERM and EPISKINassays and the Skin Integrity Function Test (SIFT). Thisvalidation study, which aims at the replacement of thetraditional Draize rabbit skin test, will take place in2003.

A survey was organised, in collaboration with the Euro-pean Chemicals Bureau, which involved the NationalCoordinators for Testing Methods and the CompetentAuthorities of the EU Member States, to establish theuses of alternative methods for eye irritation formallyaccepted by regulatory authorities. The survey led to arecommendation to carry out weight-of-evidence re-views on some in vitro methods so that they could bevalidated and accepted into regulation.

Two collaborative studies on skin irritation testing withnon-invasive technology and on phototoxic potency te-sting were initiated.

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THE ECVAM SCIENTIFIC INFORMATION SERVICE (SIS)

In line with its institutional duties ECVAM has esta-blished and maintains the Scientific Information Servi-ce (SIS) to disseminate factual and evaluated (ready-to-use) information on advanced alternative methodsfor toxicology assessments. SIS mainly provides fullmethod descriptions, including their development andvalidation status, the test protocols for their perfor-mance , and information on test results.

The year 2002 has seen the further consolidation ofECVAM as an information centre. The SIS reached 1500active registered users to its online databases. Ananalysis of statistics and a questionnaire is under deve-lopment. At the same time, the information contents ofSIS is continuously being updated in various fields of invitro toxicity testing carried out in collaboration withvarious European Institutes.

Moreover, ECVAM established its web site and made itavailable on the Internet at the address: http://ecvam.jrc.it, which offers, among others, numerous documen-ts for download related to ECVAM’s work and is linked toSIS databases.

The 1st version of the ECVAM Thesaurus project, a syste-matically ordered collection of harmonised terms, isbeing prepared for its online availability for practicalapplication by the end-user. This project was a result ofa collaboration with the Head of the Thesaurus sectionof the US National Library of Medicine, the world lea-ding authority in the area of thesauruses applied tobiomedical sciences.

OTHER ACTIVITIES

ECVAM Workshops & Task Forces

ECVAM workshops are held to review the current statusof various types of alternative tests and their potentialuses, and to identify the best way forward. Task Forcesfocus on more tightly defined targets. In 2002 two me-etings of ECVAM Task Forces on Skin Irritation and Hor-mones, were held as well as the Workshop on the ThreeRs Approaches in the Quality Control of Rabies Vacci-nes.

Good Laboratory Practicesand Good Cell Culture Practices

In the course of executing its mission to validate in vi-tro methods as alternatives for conventional animal te-sting, ECVAM has been the catalyst in considering qua-lity control issues for in vitro studies in general. Basedon an ECVAM workshop on 'The principles of good labo-ratory practices: application to in vitro toxicology stu-dies', OECD initiated the set-up of a task force for consi-dering the issuing of an OECD Guidance document on“Good Laboratory Practices (GLP) and in vitro toxicolo-gical studies”. The Interagency Coordinating Commit-tee for Validation of Alternative Methods (ICCVAM) inthe United States, through its GLP Subcommittee, sha-res these goals and therefore, both ECVAM and ICCVAMare collaborating strongly on this topic.

The maintenance of high standards is fundamental toall in vitro sciences and therefore, ECVAM continues topromote this spirit by the recent publication of anECVAM Task Force Report on Good Cell Culture Practices.

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MAJOR EVENTS

The ECVAM Status Seminar

A little bit more than ten years after the establishmentof ECVAM, the Unit organised a Status Seminar to criti-cally review the contributions of ECVAM to its four mainduties and to identify priorities for future activitieswith regard to these tasks and with emphasis on the EUChemicals Policy, the 7th Amendment to Directive 76/768/EEC on Cosmetics and Directive 86/609/EEC onanimal welfare. Collaborators and stakeholders ofECVAM, in addition to the ECVAM staff and members ofthe JRC, attended the seminar. The scientific program-me consisted of six sessions with 48 platform presenta-tions and a poster session. The unanimous judgementwas that ECVAM has achieved the position of an inter-national reference centre in the area of animal alterna-tives for test development and validation.

Press Conference

A stakeholder and press conference on Research intoAlternatives to Animal Experimentation and the ThreeRs concept was jointly organised by DG RTD and DG JRC.Parts of the proceedings of that conference were sub-mitted by ECVAM to DG Research.

Awards

Enrico Sabbioni received the 2002 Hevesy Medal Awardon 17th June in Antalya, Turkey, in recognition of hisoutstanding career contribution to radioanalytical che-mistry, particularly in biomedical applications over 40-year period. The Hevesy Medal Award is the premier in-ternational award of excellence to honour outstandingachievements in radioanalytical and nuclear chemistry.

SELECTED PUBLICATIONS 2002

Alternative (non-animal) methods for chemicals testing: currentstatus and future prospects. A report prepared by ECVAM and theECVAM Working Group on Chemicals. Edited by WORTH, A.P. &BALLS, M. (2002) ATLA 30, supplement 1

The proceedings of the ECVAM Status Seminar "Alternatives to Ani-mal Experiments: Progress Made and Challenges Ahead", 4-6 June2002, JRC Ispra, Italy. Edited by BALLS M. (2002). ATLA 30, sup-plement 2

GRIBALDO L, ALISON M, ANDREWS P., BREMER S., DONOVAN P.,KNAAN SHANZER S., MERTELSMANN R., SPIELMANN H., TESTA N.,TRIFFITT J., ZIPORI D. & DEWYNTER E. Meeting summary: Europeanworkshop on stem cells, European Centre for the Validation of Bio-medical Testing Methods, Institute for Health and Consumer Pro-tection, Joint Research Centre, Ispra, Italy, November 21-23,2001. Experimental Hematology 30, 628-633

GENSCHOW E. SPIELMANN H., SCHOLZ G., SEILER A., BROWN N.,PIERSMA A., BRADY M., CLEMANN N., HUUSKONEN H., PALLIARDF., BREMER S. & BECKER K. (2002) The ECVAM International Valida-tion Study on In Vitro Embryotoxicity Tests; Results of the DefinitePhase and Evaluation of Prediction Models. ATLA 30, 151-176.

HALDER, M., HENDRIKSEN, C.F.M., CUSSLER, K. & BALLS, M.(2002). ECVAM’s contribution to the implementation of the ThreeRs in the production and quality control of biologicals. ATLA 30, 93-108

HARTUNG, T., BALLS M., BARDOUILLE C., BLANCK O., COECKE S.,GSTRAUNTHALER G., LEWIS D. (2002). ECVAM Good Cell CulturePractise Task Force Report 1. ATLA 30, 404-444

PAZOS P., FORTANER S., PRIETO P. (2002). Long-term in vitro toxic-ity models: comparison between a flow cell bioreactor and staticcell cultures based on membrane technology. ATLA 30(5): 515-523

MAZZOTTI F., SABBIONI E., PONTI J., GHIANI M., FORTANER S., &ROSSI G. L. (2002). In vitro setting of dose-response relationshipsof 32 metal compounds in the Balb/3T3 Cell Line, as a basis for pre-dicting their carcinogenic potential. ATLA 30, 209-217

ZUANG, V., BALLS, M., BOTHAM, P.A., COQUETTE, A., CORSINI, E.,CURREN, R.D., ELLIOTT, G.R., FENTEM, J.H., HEYLINGS, J.R., LIEB-SCH, M., MEDINA, J., ROGUET, R., VAN DE SANDT, J.J.M., WIE-MANN, C. & WORTH, A.P. (2002) Follow-up to the ECVAM Prevalida-tion Study on In Vitro Tests for Acute Skin Irritation. ECVAM SkinIrritation Task Force Report 2. ATLA 30, 109-129

CONTACTS

Head of UnitThomas HartungTel.: +39 0332 786256Fax: +39 0332 785336thomas.hartung@cec.eu.int

Acute and Systemic ToxicitySilvia CasatiTel.: +39 0332 786445Fax: +39 0332 785336silvia.casati@jrc.it

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

Biologicals and PECOMarlies HalderTel.: +39-0332785550Fax: +39-0332785336marlies.halder@jrc.it

Carcinogenicity and Metal ToxicityEnrico SabbioniTel.: +39 0332 789070Fax: +39 0332 785994enrico.sabbioni@jrc.it

Haematotoxicity and Anticancer DrugsLaura GribaldoTel.: +39 0332 789267Fax: +39 0332 785336laura.gribaldo@jrc.it

Metabolism and Neurotoxicity,Pyrogenicity and Immunotoxicity testing and GLPSandra CoeckeTel.: +39 0332 789806Fax: +39 0332 785336sandra.coecke@jrc.it

Molecular BiologyRaffaella CorviTel.: +39 0332 785266Fax: +39 0332 785845raffaella.corvi@jrc.it

Nephrotoxicity, Barriers and Long-Term ToxicologyPilar PrietoTel.: +39 0332 78 5534Fax: +39 0332 785336maria.prieto-pilar@jrc.it

Reproductive Toxicology and CardiotoxicitySusanne BremerTel.: +39 0332 785914Fax: +39 0332 785336susanne.bremer@jrc.it

The ECVAM Scientific Information Service (SIS)Annett Janusch RoiTel: +39 0332 785570Fax: +39 0332 785845annett.roi@jrc.it

Topical Toxicity and Human StudiesValèrie ZuangTel.: +39 0332 785843Fax: +39 0332 785336valerie.zuang@jrc.it

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Institutional ProjectChemical products, environment risk assessment

Web information resourcesAt IHCP site

http://ihcp.jrc.cec.eu.int/NEW_ACTIVITIES/ACTIndex.htmlAt the European Chemicals Bureau site

http://ecb.jrc.it/

ce bce bEuropean Chemicals Bureau

The ECB provides scientific and technical support to theconception, development, implementation and monito-ring of EU policies on dangerous chemicals. The ECBsupports the development and harmonisation of testingmethods; the legal classification and labelling of sub-stances; the management of risk assessment of sub-stances; the notification of new substances; the autho-rization of dangerous biocides; and the informationexchange on import and export of dangerous substan-ces. Directives supported are 67/548/EEC, 93/67/EEC,96/56/EC, 97/56/EC, 98/8/EC and the regulations are2455/92, 793/93, and 484/94.

Main partners of the ECB are the authorities of the EUMember States and Norway, Commission services (suchas DG Environment and DG Enterprise), the chemical in-dustry, and NGOs. The ECB manages and chairs around40 meetings per year with the aforementioned stake-holders.

The New EU Chemicals Policy

The recent White Paper on the Strategy for a future Che-micals Policy (COM (2001) 88 final) presents the Com-mission proposals for a new EU chemicals policy. TheIHCP (the ECB and ECVAM) will play a central role in theestablishment of this policy through the:

• Further expansion of activities in this field includingthe responsibility for approximately 100,000 regi-strations on 30,000 chemicals.

• Establishment of a central system of Registration,Evaluation, and Authorisation of CHemicals–the so-called REACH-IT system–to host all chemicals data andto support the authorities of the EU Member States.

• Restriction and authorisation procedure on chemi-cals of high concern.

• New testing strategy using alternative tests.

The following sections will focus on a) the process ofthe evaluation of (existing and new) substances; b) theauthorization of biocides; and c) the informationexchange on import/export of dangerous substances.

THE PROCESS OF THE EVALUATION OF SUBSTANCES

There is an arbitrary distinction between ‘existing’ and‘new’ substances in Europe, which affects the evalua-tion process. Existing substances are defined as thosesubstances that were already on the EU-market, and li-sted in the European Inventory of Existing CommercialSubstances (EINECs) by 18 September 1981–an inven-tory containing 100,000 substances. New substancesare those placed on the EU market for the first time af-ter 18 September 1981. These new substances must benotified before being placed on the market, after whichthey are registered in the European List of Notified Che-mical Substances (ELINCs).

In contrast to the new substances, existing substanceshave never been subjected to a systematic testing regi-me. When the requirement for testing and notificationof ‘new’ substances was introduced in 1981, substancesalready on the market were exempted. Only in 1993, theCouncil Regulation 793/93 introduced a framework forthe evaluation and control of ‘existing’ chemical sub-stances, thereby complementing the already existingrules for new substances governed by Council Directive67/548/EEC.

The ECB supports the three first steps of Council Regu-lation EEC 793/93: data collection, priority setting, andrisk assessment of substances. In consultation with EUMember States the Commission must regularly draw uplists of priority substances, on the basis of collected in-formation, taking into account their potential effectsto humans or the environment.

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European Chemicals Bureau (ECB)

Relevant EC legislation on Substances

Directive 67/548/EEC Classification & Labelling, Notifications, Testing Methods

Directive 93/67/EEC Risk Assessment New Substances

Directive 98/8/EC Biocides

Regulation (EEC) 793/93 Existing Substances

Regulation (EC) 1488/94 Risk Assessment Existing Substances

Regulation (EEC) 2455/92 Export/Import

Directive 76/769/EEC Restriction on Marketing and Use

Directive 91/414/EEC Plant Protection Products

The following sub-sections describe in more detail thestages of the evaluation process of substances.

The harmonization of Testing Methods

Harmonized testing methods must exist in order to eva-luate the properties of various substances. The ECB isresponsible for the technical and scientific work neededfor the development, introduction, and adaptation totechnical progress of testing methods of Annex V to Di-rective 67/548/EEC (and its adaptations). Annex V con-tains standardized testing methods for the determina-tion of the intrinsic properties of chemical substances,which allow for the characterization of potential hazar-ds for people and the environment. Data provided bytesting methods constitute the basis for a proper classi-fication and labelling of chemicals and for risk character-ization. Moreover, the use of these standardized methodsensures the mutual acceptance of data, and the free cir-culation of goods between countries. The ECB activitiesin this area are coordinated with the OECD and otherinternational organizations.

In 2002, the main achievements in introducing orupdating testing methods were the:

• 6 additional new or updated methods were preparedfor Annex V, including several new or revised alterna-tive methods (reduction and refinement) and upda-ting of animal tests including new strategies to redu-ce animal use.

• 7 methods in preparation, including four new or revisedin vitro methods.

• An interim strategy allowing the use of some in vitromethods for eye irritation was approved.

• Further development of methods for MMMF: Closureof the first phase of the 90 days inhalation study, ascientific paper summarizing the results in prepara-tion. New method for LWGMD finalized.

• Electronic informal versions of all (85) in force AnnexV methods were produced and made available in theECB web site.

• A guidance document on granulometry of chemicalsubstances was published.

Legal classification and labelling(existing and new substances)

The ECB is in charge of technical and scientific issuesfor the Adaptation to Technical Progress (ATP) of An-nexes I, II, III, IV, VI, and IX to Council Directive67/548/EEC on the classification, packaging and label-ling of dangerous substances. The ECB’s work entailsthe preparation, chairing and follow-up of meetings ofthe Commission Working Group on Classification andLabelling (composed of experts from EU Member Statesand observers from the EEA Member States, industryand NGOs); the co-ordination of meetings between EUMember States and industry and the provision of infor-mation to other Commission services.

The 29th ATP preparations were initiated during 2002.The ATP will include – besides new testing methods - anupdated foreword to Annex I (Note K), together withapproximately 220 new or revised Annex I entries forexisting substances, 382 entries for new substancesand 16 entries for confidential pesticides.

A technical working group, chaired by the ECB, was setup to prepare the implementation of the Globally Har-monised System (GHS) of classification and labellingwithin the Community in the context of the White Paperon a future chemical policy.

Risk assessment for existing chemicals

All substances (existing and new) on the priority listmust undergo an in-depth risk assessment to examinethe risks posed to humans and the environment (terre-strial, aquatic and atmospheric eco-systems). The riskassessment follows the framework set out in Regulation1488/94, and implemented in the detailed TechnicalGuidance Documents on Risk Assessment for New andExisting Substances.

The first draft of the risk assessment reports are prepa-red by the Member State which acts as ‘rapporteur’, andis submitted to the Technical Meetings for discussion.The ECB mediates the technical meetings, which at-tempt to reach consensus on the conclusions of the riskassessment. After adoption of the risk assessment,three publications on Existing chemicals are produced:

• Comprehensive risk assessment report (2 formats):IUCLID and ECB homepage.

• Summary: ECB homepage.• Conclusions in the Official Journal or the European

Communities.

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Main achievements in 2002 were:

• The discussions at the Technical Meeting on the riskassessment were finalised for 10 additional substan-ces, bringing to a total of 76 the number of prioritysubstances that have been risk assessed since thebeginning of the ESR programme.

• The work area completed the preliminary screening ofthe IUCLID database for potential PBTs and vPvBs.

• 25 additional comprehensive EU Risk Assessment Re-ports were published on the Internet in 2002.

• Two Commission Regulations and three CommissionRecommendations were published in 2002, for whichthe work area had carried out the preparatory work,provided the scientific justification and had preparedthe draft texts.

• The Existing Substances Information System, a com-prehensive tool for supplying information related tothe Existing Substances Regulation went on-line in2002.

• 2 training courses regarding IUCLID and the EU riskassessment procedures were carried out.

The notification and risk assessmentof new chemicals

All new chemicals have to go through the notification(and risk assessment) process, as laid down in the Di-rectives 67/548/EEC and 93/67/EEC.

Over 5600 notifications in total, including over 3500new chemical substances, have been submitted since1983, currently an average of 400–450 notificationsand 300–350 substances are processed per year. Irres-pective of notification date, during the year 2002 so-mewhat fewer notifications were submitted to ECB,compared to the previous year and in contrary to atrend of steadily increasing numbers over several recentprevious years.

Over half have been combined contributions from Uni-ted Kingdom and Germany. Respecting substance ori-gins, over half of new substances marketed in the EUduring the year 2002 were foreign imports, principallyfrom Japan, USA, and Switzerland. UK takes a primaryrole concerning imports with Germany representing aprincipal Member State for EU domestic manufacture.

About one third of notifications submitted since adop-tion of the 7th Amendment of the Directive are completewith risk assessment. No risk assessment is normallyavailable for substances which are not classified (~30%)and for reduced notifications according Annex VIIC.

* Human Health part of the report to be finalised in 2003.

Risk assessment reports of existing chemicals finalised in 2002

SUBSTANCE CAS N> Member State

2-ethylhexyl acrylate 103-11-7 D

4'-tert-butyl-2',6'-dimethyl-3',5'-dinitroacetophenone 81-14-1 NL

5-tert-butyl-2,4,6-trinitro-m-xylene 81-15-2 NL

Benzene 71-43-2 D

Benzyl butyl phthalate 85-68-7 N

Cadmium 7440-43-9 B

Cadmium oxide 1306-19-0 B

Chloroacetic acid 79-11-8 NL

Perboric acid, sodium salt * 11138-47-9 A

Phenol * 108-95-2 D

The following table shows the risk assessment reports ofexisting substances that were finalised in 2002, and theMember State that acted as ‘rapporteur.’

THE AUTHORIZATION OF BIOCIDES

Biocides are chemical preparations containing one ormore active substances that are intended to controlharmful organisms (such as pest control).

The Directive 98/8/EC concerning the placing of bioci-dal products on the market harmonizes the rules of suchplacement by introducing common data requirementsfor both active substances and biocidal products.

A first Review Regulation, Regulation (EC) No.1896/2000 addressing the review of existing active su-bstances was agreed on 7th September 2000, enteringinto force on 28th September 2000. This regulation gi-ves a period for either notification of supported acti-ve substances or identification of non-supported ac-tive substances by 28th March 2002.

Regulation (EC) No. 1687/2002 was adopted on 25th

September 2002, entering into force on 15th October2002 giving an additional period until 31st January2003 to notify active substances that have only beenidentified and to add product types to the already noti-fied substances.

During 2002 the second review regulation, which is tophase out non-supported substances and inform aboutthe order in which the product types are reviewed andgive the rapporteur member states for the first 2 blocksof product types to be reviewed, was extensively di-scussed at CA level.

To prepare for the review programme the following taskswere undertaken in year 2002:

• The web page for biocides, http://ecb.ei.jrc.it/biocides, has continuously been updated, to enableindustry to check that their information is registeredcorrectly and to distribute information to thirdparties.

• The TNsG on Annex I, IA or IB Inclusion was finalisedand placed on the web.

• The TNsG on Product Evaluation was finalised andplaced on the web.

• The TNsG on Human Exposure to in Biocidal Products– Guidance on Exposure Estimation was finalised andplaced on the web.

• The TNsG on Dossier Preparation and Study Evalua-tion was finalised and placed on the web.

• 3 IUCLID courses were successfully given to authori-ties of the member states, candidate countries andindustry.

• The biocides team participated in numerous eventsand conferences aiming at explaining the BiocidesDirective, the first review regulation and its conse-quences.

• The different technical guidance documents were fur-ther progressed; a second one on environmentalemission scenarios for biocides was initiated.

35

D 24%

UK 27%

F 12%

NL 9%

I 8%

B 6%

IRL 4%E 3%

P 2%DK 2%

S 1%Others 2%

Cumulative notification contributionsfor new chemicals per Member State

(1983-2002)

Recent annual notificationsubmissions to ECB

(1997 to 2002)

0

100

200

300

400

500

600

Notifications Updates Final C&Lproposals

348

399 43

247

5 506

178

262

309

425

539

259

167

302

227

316

489

402

189

199719981999200020012002

36

THE INFORMATION EXCHANGE ON IMPORTAND EXPORT OF DANGEROUS SUBSTANCES

The ECB fulfils the duties of the Commission within theexport notification process as laid down in Regulation2455/92 by giving technical and scientific support forthe implementation of the Regulation. The main issuesof the Regulation are: to implement the EU export noti-fication procedure; to make the voluntary UNEP/FAOPrior Informed Consent (PIC) procedure legally bindingwithin the Community; and to use the same rules forclassification, packaging and labelling outside theCommunity that apply in the internal market.

At the international level, a new regulation called theRotterdam Convention was signed in September 1998,and is still in the process of ratification. The voluntaryimplementation of the Rotterdam Convention withinthe EU established the ECB as the central export notifi-cation authority on behalf of the Community. The Euro-pean Database on EXport and Import of certain dange-rous chemicals (EDEXIM) was modified to meet the newrequirements during the interim period until the Con-vention will be legally binding.

All relevant Export Reference Numbers (ERNs) assignedwithin the EU export notification procedure, were pu-blished in the Official Journal twice during the year inall the official languages of the Community.

During 2002 a new regulation on Import/Export wasbeing prepared to be in accordance with the require-ments of the Rotterdam Convention.

The ECB continues to develop the National Profile Ho-mepage in collaboration with the United Nations Insti-tute for Training and Research (UNITAR). This Internetsite has information on the existing national legal, in-stitutional, administrative and technical infrastructurerelated to the sound management of chemicals forover 45 countries. The Internet address is: http://www.unitar.org/cwm/nationalprofiles/index.htm.

In addition, the ECB is actively supporting the develop-ment of several services within the INFOCAP project inthe regime of the Intergovernmental Forum on Chemi-cal Safety (IFCS). In 2002 the ECB has actively contri-buted to the two services of the INFOCAP by developing4 internet sites for each service, allowing almost auto-managed information systems according with the stee-ring group indications.

RESEARCH ACTIVITIES

OMNIITOX project(EC project number: G1RD – CT2001 – 00501)

The project OMNIITOX (Operational Models aNd Infor-mation tools for Industrial applications ofeco/TOXicological impact assessments) aims to enhan-ce the capability of industry to select more environ-mentally benign chemicals and processes. The projectinvestigates refinement of environmental impact mana-gement for chemicals, incorporating Life Cycle Assess-ment (LCA) concepts. The approach has a comprehensi-ve scope, beyond traditional substance specific RA,including web-based information retrieval. In collabo-ration with other partners, ECB leads a feasibility studyof introducing elements and concepts of the LCA fra-mework into the regulation of chemicals. The main acti-vity in 2002 has been an LCA case study, comparing ap-plication of metal working fluids with and withoutchlorinated paraffins.

Review of EU Risk Assessment (RA)methodology for paper recycling

Risk Assessment (RA) for a new substance used as a sol-vent in carbonless copy paper has revealed uncertain-ties in the scenario of paper recycling. The RA has rai-sed a wider issue concerning the validity of RAmethodology relating to paper recycling. The projecthas undertaken to review this methodology by refiningthe RA for the new substance respective of paper re-cycling and through comparative survey of analogousRAs with this exposure scenario, available from notifiedsubstances registered in the new chemicals database(NCD).

A new JRC Activity on QSARs

Structure-activity relationships (SARs) and quantitativestructure-activity relationships (QSARs), collectivelyreferred to as (Q)SARS, are theoretical models that canbe used to predict the physicochemical and biologicalproperties of molecules. A SAR is a (qualitative) asso-ciation between a chemical substructure and the poten-tial of a chemical containing the substructure to exhibita certain biological effect. A QSAR is a mathematicalmodel that relates a quantitative measure of chemicalstructure (e.g. a physicochemical property) to a physi-cal property or to a biological effect (e.g. a toxicologi-cal endpoint).

The general aim is to promote the development, valida-tion and implementation of (Q)SARs that will be usefulfor regulatory purposes, in particular on the needs ofthe future EU legislation on chemicals (REACH system).The work is performed in close collaboration withECVAM.

SELECTED PUBLICATIONS 2002

BARAIBAR FENTANES J., COLE, T., NORAGER O., OLSSON, H.,SOKULL-KLÜTTGEN, B., MARAS, K. (2002): DES for Windows(version 6.1) – Data entry screens for notification summarieson new chemical substances (Directive 67/548/EEC). Softwareto be obtained by ECB

COLE, T., OLSSON, H., SOKULL-KLÜTTGEN, B. (2002): Manual ofDecisions for implementation of the sixth and seventh amend-ments of Directive 67/548/EEC on dangerous substances (Direc-tives 79/831/EEC and 92/32/EEC). At http://ecb.jrc.it/new-chemicals/

The following publications regarding EU Risk Assessment on Ex-isting Substances are available at http://ecb.jrc.it/existing-chemicals:

HANSEN, B.G., MUNN, S.J., DE BRUIJN, J., PAKALIN, S., LUOTA-MO, M., BERTHAULT, F., VEGRO, S., HEIDORN, C.J.A., PEL-LEGRINI, G., VORMANN, K., ALLANOU, R., SCHEER, S., EDITORS(2002): 4-Nonylphenol (branched) and nonylphenol, 2nd PL,Volume 10. EUR 20837 EN

HANSEN, B.G., MUNN, S.J., PAKALIN, S., HEIDORN, C.J.A., AL-LANOU, R., SCHEER, S., PELLEGRINI, G., VEGRO, S., DE BRUIJN,J., LUOTAMO, M., VORMANN, K., LOONEN, H., BERTHAULT, F.,PRADERIO, L., Editors (2002): 4-Choro-o-cresol, 1st PL, Volume11. EUR 19757 EN

HANSEN, B.G., MUNN, S.J., LUOTAMO, M., PAKALIN, S., BER-THAULT, F., DE BRUIJN, J., VEGRO, S., PELLEGRINI, G., AL-LANOU, R., SCHEER, S., Editors (2002), Volume 12-15, 17:Dimethyl Sulphate, 2nd PL, EUR 19838 ENEthyl acetoacetate, 1st PL, EUR 20396 ENDimethyldioctadecylammonium chloride, 1st PL, EUR 20397 ENo-Anisidine, 2nd PL, EUR 19834 ENBis(pentabromophenyl) ether, 1st PL, EUR 20402 EN

HANSEN, B.G., MUNN, S.J., LUOTAMO, M., MUSSET, C., PAKA-LIN, S., DE BRUIJN, J., BERTHAULT, F., VEGRO, S., PELLEGRINI,G., ALLANOU, R., SCHEER, S., Editors (2002), Volume 18-25, 27:Acetonitrile, 1st PL, EUR 19839 ENTert-Butyl methyl ether. 3rd PL, EUR 20417 EN1,3-Butadiene, 1st PL, EUR 20420 EN1,4-dioxane, 2nd PL, EUR 19833 ENMethyl methacrylate, 1st PL, EUR 19832 ENMethyloxirane, 2nd PL, EUR 20512 ENAcrylamide, 1st PL, EUR 19835 ENMethacrylic acid, 1st PL, EUR 19837 ENStyrene (environment), 1st PL, EUR 20541 EN

HEIDORN, C. J. A., RASMUSSEN, K., HANSEN, B. G., NØRAGER,O., ALLANOU, R., SEYNAEVE, R., SCHEER, S., KAPPES, D. andBERNASCONI, R.: IUCLID: An Information Management Tool forExisting Chemicals and Biocides. Accepted for publication inJournal of Chemical Information and Computer Sciences, Dec.2002

LAHANIATIS, M.R., PAKALIN, S. AND KETTRUP, A.,“Environmental and Human Health Risk Assessment” in Fresen-ius Environmental Bulletin, Vol. 11, No. 10a, 713-735, 2002.ISSN 1018-4619

KAPPES, D. and RASMUSSEN, K.: Progress on the Biocides Direc-tive. Accepted for publication in Pesticides Outlook, December2002.

37

Another collaboration between ECB and ECVAM has be-en initiated on the evaluation of in vivo data on newsubstances relevant to development and validation onin vitro skin irritation assay, relating to R38 classifica-tion. Screening of notified substances registered in NCDallows selection of candidate substances for experimen-tal study, and provides quality controlled in vivo datafor comparative validation of alternative in vitromethods. Furthermore, similar activities to use data ofthe NCD were initiated with respect to teratogenicityand neurotoxicity.

MUNN, S.J. AND HANSEN, B.G.: “EU Risk Assessment: Scienceand Policy” in Toxicology. In Print

RASMUSSEN, K. and KAPPES, D.: Implementation of the Biocid-al-Products-Directive: Technical Notes for Guidance in Support ofDirective 98/8/EC. Accepted for publication in Chimica Oggi,July 2002

RIEGO SINTES, J.; Editor (2002). Guidance Document on the De-termination of Particle Size Distribution, Fibre Length and Diam-eter Distribution of Chemical Substances. Luxembourg: Office forOfficial Publications of the European Communities. EUR 20268EN. ISBN 92-894-3704-9

RIEGO SINTES, Juan M.: “La evaluación de las substanciasquímicas en la Unión Europea: Introducción a los métodos deensayo”, in: Repetto, M. editor, “Toxicología de Postgrado”.Área de Toxicología. ISBN 84-699-6978-1. Universidad de Se-villa. CD-ROM. Sevilla 2002

SOKULL-KLÜTTGEN, B., COLE, T., JOHANSSON, S., OLSSON, H.(2002): Notification of new chemical substances in accordancewith Directive 67/548/EEC on the classification, packaging andlabelling of dangerous substances - Technical Guidance for thecompletion of a summary notification dossier for a new chemicalsubstance utilising the Structured Notification Interchange For-mat (SNIF) - Base-set and levels 1 and 2.At http://ecb.jrc.it/new-chemicals/

WEYERS, A., RÖMBKE, J., MOSER, T., RATTE, H.T. (2002): Statis-tical Results and Implications of the Enchytraeid ReproductionRingtest. Env. Sci. Technol. 36 : 2116-2121

CONTACTS

Head of UnitGerald VollmerTel.: +29 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 labeling & Export/ImportElisabet BerggrenTel.: +39 0332 789065Fax: +39 0332 789963elisabet.berggren@jrc.it

Ingrid LangezaalTel.: +39 0332 786135Fax: +39 0332 789963ingrid.langezaal@jrc.it

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

IUCLID databaseStefan ScheerTel.: +39 0332 785683Fax: +39 0332 785862Stefan.scheer@jrc.it

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

38

Institutional ProjectUV-Radiation, Noise, Indoor Exposure,

Electromagnetic Fields

Other ActivityFood Contact Materials

Toxicological Evaluation of Chemicals

Web information resourcesAt IHCP site

http://ihcp.jrc.cec.eu.int/NEW_ACTIVITIES/ACTIndex.html

Physical and Chemical Exposure

cp ecp e

40

The mission of the Unit is to provide scientific under-standing, information and assessment tools to supportthe Commission services in evaluating and quantifyinghuman exposure and risk assessments for environmen-tal stressors. Stressors include chemicals, biologicalcontaminants, UV-radiation and noise.

As a result of the restructuring process, on 1st Septem-ber 2001, the PCE Unit was transferred from the Insti-tute for Environment and Sustainability (IES) to the In-stitute for Health and Consumer Protection (IHCP). Thechange was in close agreement with the overall missionof the Unit “to support the Commission Services in hu-man exposure and risk assessment issues”. Other sectorsfrom IHCP joined the PCE Unit with the aim to combineefforts, in particular regarding the application of meth-ods, of chemical/analytical and toxicological tech-niques, to improve human exposure and risk assessmentfor environmental stressors.

The UNIE-project (UV-radiation, Noise,Indoor Exposure, Electromagnetic Fields)

To accurately evaluate the health risk of European citi-zens from the exposure to environmental stressors, in-cluding chemicals, biological contaminants, UV-radiation and electromagnetic fields, the Commissionrequires sound scientific knowledge on occurrence,source strengths, dispersion and fate as well as reliabledata on exposure of the population to these stressors.

Currently there is abundant evidence among expertsand policy makers that human exposure data representa major bottleneck in the risk assessment process. Thishas been recognised by the EU Council of the Environ-mental Ministers who requested the EU Commission toundertake action for eliminating existing deficienciesin exposure data.

In the frame of the UNIE project, a holistic approach istaken towards human exposure, including estimatesand assessment of exposure due to the impact of chem-ical, biological and physical agents as the basis for thedevelopment and implementation of:

• Common measurement methods and protocols• Common exposure models• Exposure guidelines

Chemicals

During 2002 activities on chemicals mainly focussed toevaluate existing needs in exposure data, particularlyon chemicals released from consumer products and arti-

cles. The overall scope was to create an operationalplatform for the analysis of the problem using availableinformation from relevant partners, from the industryand scientific institutions and to define the way to fillin existing gaps. To this end, a workshop was organisedon behalf of DG SANCO (17th June 2002) with the par-ticipation of all relevant stakeholders from industry,academia and international organisations and with theparticipation of decision and policy makers, with theaim to evaluate the current situation and to identifyconcrete policy needs. With the participation with DGSANCO, two main projects (EIS-CHEMRISKS and CHEM-TEST) have been formulated and approved as European-wide networks to systematically exchange and assessinformation on emerging issues related to “Risks fromchemicals released from consumer products andarticles”. The efforts of the PCE Unit on this subject willfocus on filling the exposure gaps in a systematic, co-herent manner, integrating current knowledge withnovel state of the art approaches to determine andquantify the release of chemicals from prod-ucts/articles. This work will substantially support theRAPEX notifications of the General Product Safety Di-rective and provide technical support to the relevantaspects of REACH in the frame of the New ChemicalsPolicy.

Tobacco Directive

One of the objectives of UNIE was to provide support(DG SANCO) for the implementation of the new TobaccoDirective, in particular, regarding the question of addi-tives and pesticide residues in tobacco products. During2002 various tobacco (cigarette) brands were analysedfor their content in cations, anions, urea and pesticideresidues. Emphasis was given to identifying and quanti-fying additives, e.g. ammonia released compounds(ammonium salts, urea), which might routinely be add-ed to the tobacco used for cigarettes to increase as wellas to control the delivery of nicotine to the respiratorytract of the smoker. Ammonia reacts with the indige-nous nicotine salts and liberates free [base] nicotine.Ammonium concentrations in the investigated ciga-rette brands range from 0.07 to 0.49 g/100 g of tobac-co. Urea has been found in three brands only, at levelsbetween 6 and 20 mg/100 g.

The amount of pesticides appearing in mainstreamsmoke may vary from 10 to 20 % of the amount presentin a cigarette. From the findings in our studies, it is es-timated that up to 30 ng pesticides/cigarette can betaken up by the inhaling smoker. The daily intake of themost common pesticides (including the pesticidesfound in our studies) appearing in tobacco smoke by

Physical and Chemical Exposure Unit (PCE)

the one-pack-per-day inhaling smoker amounts to ca.0.75 µg/day.

The results obtained from the analysis of ten cigarettebrands can be seen as preliminary. However, they clear-ly indicate the necessity for further investigations, asrequested in the frame of the implementation of thenew tobacco directive.

Inter-comparison of different types ofpassive samplers for volatile organic compounds (VOC)

In the last few years several types of passive (diffusion)samplers for volatile organic compounds have beenmade commercially available, and have been widelyused for measurements in indoor and outdoor environ-ments. However, hardly any data exist on the compara-bility of the various types of samplers. We have studiedthe sampling capacity of passive samplers for aromaticcompounds (benzene, toluene, m/p-xylenes, o-xylene)under well-defined experimental conditions in theINDOORTRON facility (working concentrations: 50-60µg/m3 for benzene, toluene and o-xylene and 110-125µg/m3 for m/p-xylenes) and exposing them in the labo-ratory atmosphere for up to four weeks.

The following passive sampling devices were tested:

• Radiello I: (CS2 elution)• Radiello II carbograph : (thermal desorption)• SKC: (CS2 elution)• Draeger ORSA: (CS2 elution)• Perkin Elmer: (thermal desorption)

Under the conditions in our study, preliminary evidenceindicates that Radiello I, SKC and the Perkin Elmer pas-sive samplers are better suited for the sampling of aro-matic compounds. The average values obtained withthe three aforementioned passive samplers show anoverall variation of 10-15% of the default value, whilefor the other two samplers Radiello II and Draeger ORSAvariations, which ranged for e.g. benzene from 20-50%of the default value, were measured. Experiments willbe continued, under various conditions of temperatureand humidity, including other groups of compounds(aliphatic, olefins).

Photo-induced degradation of gaseous pollutantson photo-catalytic surfaces containing titaniumdioxide (PICADA)

The photo-catalytic properties of TiO2 are well knownsince several years. Numerous studies report on thedegradation of persistent organic compounds in e.g.water solutions when irradiated in the presence of TiO2.In the frame of the project PICADA the photo-catalyticactivity of TiO2, added to different building materials,such as concrete, for the degradation of inorganic (NO,

NO2, O3) and organic compounds (VOCs) has been test-ed. The experiments are carried out using the INDOOR-TRON facility and will be finalised during 2003. Prelim-inary results indicate high conversion rates (up to 60%)for, particularly, NO on TiO2 surfaces.

Harmonisation of indoor material emissionlabelling systems in the EU

A progress report has been issued on “Harmonisation ofindoor materials emission labelling systems in the EU”.In this report a state of the art review of the existinglabelling schemes in Europe has been performed, whichhas as outcome the classification of the different sys-tems. Within this state of the art review all aspects ofthe different existing labelling systems have been elab-orated. Besides the targeted compounds and analyticalprocedures, also aspects of quality assurance and eco-nomics, like market acceptance, have been taken intoconsideration. This progress report provides an over-view of existing labels and also stresses the major ob-jectives for further needs in harmonisation.

An interim report on “Establishing a database of out-door and indoor CO source emissions and validating COexposure data for the city of Milan” was prepared in thecontext of the development and validation of an urbanair pollution micro-environmental exposure model.

European Collaborative Action (ECA):Urban Air, Indoor Environment and Human Exposure

For over 12 years the European Collaborative Action ECA"Indoor Air Quality & it's Impact on Man" has been im-plementing a multi-disciplinary collaboration of Euro-pean scientists for healthy and environmentally sus-tainable buildings. The ECA has been hosted by theJRC/EI Air Quality Unit and managed by an independentscientific Steering Committee. In order to establish a

41

Special exposure chamber positioned in the INDOORTRON for measuringthe photo-induced degradation (UB-A) of gaseous pollutants on photo-catalytic surfaces containing TiO2.

42

more direct and mutually beneficial co-operation withthe Integrated Air Quality assessment (IAQA) pro-gramme, the ECA Steering Committee decided in 1999to broaden its scope under a new title “Urban Air,Indoor Environment and Human Exposure”. The focus ofthe renewed activity is urban and indoor air pollutionexposure assessment, seen as part of environmentalrisk assessment and considering the needs of urban andindoor air quality management.

Specific examples of the working areas of ECA are: rela-tive significance and assessment of urban outdoor andindoor sources of pollution, interaction between out-door and indoor air quality of buildings, exposure topollutants from the different outdoor and indoor sourc-es in relation to health and comfort. By addressing suchtopics ECA will lay the ground for integrated air urbanquality management to minimise exposures to air pol-lutants. It will thus continue to contribute to pre-normative research needed by EC services and nationalauthorities responsible for preventing pollution andpromoting health, comfort and quality of life.

UV Laboratory and ECUV (European ReferenceCentre for UV Radiation Measurements)

The UV laboratory provides support to specific policyactions on UV and hosts the European Reference Centrefor UV Radiation Measurements (ECUV). A network forS&T reference of solar UV radiation measurements hasbeen set up, which contributes towards the develop-ment of a total human exposure approach. The activityof the UV laboratory focuses on three topics:

• Solar UV radiation measurements• Solar UV radiation surface modelling• UV exposure and effects

Continuous measurements of total column ozone andsolar UV irradiance using two Brewer spectrophotome-ters have been continued during the year 2002. The da-ta have been reported to the UV networks, as there arethe European projects (e.g. shared cost action projectEDUCE), the WMO-GAW program and the World Ozoneand UV Data Centre (WOUDC) in Toronto.

European Reference Centre for UV Radiation Measure-ments (ECUV): An international intercomparison hasbeen successfully organised in the frame of the SharedCost Action Project QASUME and in co-operation withthe Renewable Energy Unit of the Institute for Environ-ment and Sustainability (inter-institutional co-operation). Eight thoroughly checked spectroradiome-ters from six Member States (Austria, Finland, Germany,Greece, The Netherlands, United Kingdom and two in-struments of ECUV participated at that intercompari-son. One of these instruments (Brewer) is the JRC refer-ence instrument on site and the other the transportable

standard (Bentham) of ECUV. The spectroradiometer ofthe transportable unit was compared with all instru-ments participating at the intercomparison exercise toestablish a relation, which would then be used as a ref-erence for its calibration over the period of its regularoperation at the European stations.

Different weather patterns varying from clear skies toheavy rain prevailed during the campaign, allowing theperformance of the spectroradiometers to be evaluatedunder unfavourable conditions (as may be experiencedat home sites) as well as the more desirable dry condi-tions. Measurements in the laboratory revealed that thecalibration lamps of these instruments differ by up to10%. Results of this campaign are presently being fur-ther evaluated.

The transportable standard started the first calibrationround in June and until October on site calibrationswith the JRC traveling standard have been performed atInnsbruck (A), Bilthoven (NL), Manchester (UK) andHelsinki (SF), Hannover (D) and Thessaloniki (GR). Ad-ditionally ECUV has been invited to participate during ameasurement campaign organised by the Europeanproject INSPECTRO.

International intercomparison of solar UV radiometers.

43

Mapping of UV-B exposure for the last 15 yearsin Europe

The building of the European satellite-derived UV cli-matology has been systematically pursued. It consistsin daily maps of UV radiation doses, covering the areafrom 34 to 74 N and 12E to 32E and from January 1984to October 2002. At the end of 2002 only two wintermonths were still missing and the first version of thefull data set should be completed by February 2003. Ex-tracts of these maps have been provided to the partnersin the project UVAC, studying the effects of climate onthe population strength of the North East Atlantic cod.The satellite derived UV doses have been comparedwith the measurements at Ispra, with measurements atTromsø and to higher resolution satellite derived mapsproduced by DLR (the latter two data sets being provid-ed by UVAC partners). All comparisons are comfortingwith respect to the quality of the JRC climatology.

Report on the inter-comparison of modelsfor environmental noise

A report was prepared in which guidelines and predic-tion models for road traffic and railway noise used inthe EU were compared on the basis of (a) full factsheets, which were prepared and delivered by the EU MSand (b) computer software codes used for benchmarkpurposes.

Formulation and implementation of directivesrelated to environmental noise

In the context of the HARMONOISE project (“Har-monised, Accurate and Reliable Methods for the EU Di-

rective on the Assessment and Management of Environ-mental Noise”) the 1st measurement campaign to col-lect noise & micrometeorological data, needed for thevalidation of the harmonised model under develop-ment, was prepared and successfully performed from 17to 25 October 2002 in the La Crau (France).

Development, establishment and operationof a “European Information System on publichealth protection issues related toElectroMagnetic Fields (EIS-EMF)”

The existing uncertainty in scientific information onthe impact of electromagnetic fields and the subse-quent contradictory interpretations from the scientificcommunity fail to eliminate the sense of confusion per-vasive among decision-makers. This is resulting in inco-herent legal provisions or guidelines that perpetuatethe insecurity felt by many Community citizens and un-dermines confidence in health protection authorities.During 2002 the IHCP/PCE Unit proposed the EuropeanInformation System on EMF (EIS-EMF) project as a com-mon basis for decision makers to increase the coher-ence of the approaches taken in the various MemberStates and help restore public confidence. This will sys-tematically interface and compare information fromvarious existing EIS at all levels (regional, national, in-ternational etc). In particular it will provide a Europeanadded value to international information channels,such as the WHO EMF project. The project has been ap-proved and will be financially supported by DG SANCOin order to provide an EU wide risk communication onEMF based on improving the quality of available infor-mation and broadcasting it to European citizens. Aftera phase of consultations, it will be operational during2003.

Toxicology

Major experimental activities in 2002 focused on thedevelopment of toxicogenomic approach in assessingthe exposure to environmental chemicals and chemicalmixtures. Studies were carried out applying DNA micro-array techniques to assess gene expression modulationfollowing exposure to chemical stressors. Results showthat an exposure to arsenate in drinking water indi-cates a significant gene expression differential re-sponse in male and female tissues, supporting the dif-ferent gender incidences in tumors as revealed byepidemiological studies on human populations exposedto drinking water arsenic.

Coordination activities in support to WHO-IPCS initia-tives as member of the Steering Group on EndocrineDisrupting Chemical were concluded by the finalizationof the Global Assessment Report, the implementation ofthe GEDRI database and the final report on IntegratedRisk Assessment Approach.

UV index on July 3rd 2002

44

BEVABS, European office for wine, alcoholand spirit drinks (Bureau Européen des Vins,Alcools et Boissons Spiritueuses)

In 2002 the institutional work of the BEVABS includedaspects regarding training within the frame of its newofficial laboratories and quality control of isotopicmeasurements for wines. Transfer of know-how was car-ried out through a first specific training of a NationalExpert from Austria on preparation methods for isotopicand nuclear magnetic resonance (NMR) measurementson wine in October and November 2002. The monitoringof the performance of the official Member states Labo-ratories participating to the EU wine data bank contin-ued through the FIT-Proficiency testing (Food analysisusing Isotopic Techniques network- Proficiency Testing)which welcomed new participants from Slovenia andHungary. Both countries have recently set up their ownNMR and isotopic laboratories for wines, alcohol andagricultural products. Other activities on wines havebeen carried out on wines through the competitive re-search project GLYCEROL on development and testingmethods for detection of adulteration of wine by illicitaddition of glycerol. Also a new competitive project,WINE-DB started in May involving the network of labo-ratories of the EU Wine Data bank, and new partnersfrom candidate countries (Hungary, Czech republic,Croatia and Romania). The scientific support to Com-mission DG and Member States official laboratories hasbeen continued as regards official or new analyticalmethods and interpretation of corresponding resultsand by active scientific participation in key interna-tional bodies (e.g. OIV international office for wine andvine). Ad-hoc analyses for anti-fraud purposes have al-so been carried out in support to OLAF.

BEVABS has also continued to develop new methods ap-plicable to detection of fraud, control of authenticityand verification of the origin of food and agriculturalproducts. This has been achieved mainly through workcarried out in competitive projects as for instanceMEDEO in which methods based on NMR and isotopictechniques are developed and tested for detection ofadulteration of olive oil. Similarly a new project,SPREADS, has been initiated for studying NMR measure-ments for detecting adulteration of spreadable fats. Thesame techniques have also been used in the project CO-FAWS which aims at developing analytical methods forverifying the origin of farmed and wild salmon and oth-er fish.

Contact Materials

The Contact Materials Sector specialises in safety ofchemicals regarding some consumer goods (i.e. toys),as well as food contact materials (FCM) in order to de-termine their safety and suitability for human use. In2002 the European Commission has recommended theJRC-IHCP together with a European Network of FCM lab-oratories, as the future Community Reference Laborato-ry for FCM. The IHCP will continue to support policiestoward assessment of human exposure with an empha-sis on the development and harmonisation of methods.

Activities have included pre-normative research (migra-tion into dry foods, active packaging, reaction productsfrom jar sealants, release of chemicals from toys), mon-itoring of contaminants (from toys and in baby foods),and dissemination of information (organisation of twolarge conferences on recyclability and on scientific mo-bility, and one course of mathematic modeling). Activi-ties have also included collaborative projects, ad-hoctasks in support of CEN (European Committee for Stand-ardisation) and representation in various expert groupsfor DG SANCO and DG ENTR. The activities in 2002 haveresulted in two milestones: the designation of the con-tact materials laboratories as a future Community Ref-erence Laboratory by DG SANCO, endorsed by the re-quest of Member States to lead and co-ordinate anOfficial Network of Enforcement Laboratories. Anothermilestone has been the procedure of accreditation ofthe laboratory, which has resulted in an ISO 17025 Ac-creditation in January 2003. The systematic approachused in these tasks is directed not only towards the in-tegration of the sector in the frame of risk assessmentfor consumer protection, but also to provide the scien-tific and technological tools to generate sound dataand to promote the dissemination of both legislativeand technical /scientific knowledge.

SELECTED PUBLICATIONS 2002

ALEU, J.; FRONZA, G.; FUGANTI, C.; SERRA, S.; BURKE, A.; GUIL-LOU, C. & RENIERO, F., “Differentiation of natural and syntheticphenylacetic acids by 2H-NMR of the derived benzoic acids” -Eur. Food Res. Technol. 2002, 214, 63

AROLA, ANTTI; KALLISKOTA, S.; DEN OUTER, P. N.; EDVARDSEN,K.; HANSEN, G.; KOSKELA, T.; MARTIN, T. J.; MATTHIJSEN, J.;MEERKOETTER, R.; PEETERS, P.; SECKMEYER, G.; SIMON, P. C.;SLAPER, H.; TAALAS, P.; VERDEBOUT, J., “Assessment of fourmethods to estimate surface UV radiation using satellite data,by comparison with ground measurements from four stations inEurope”, Journal of Geophysical Research Atmospheres, August28th 2002

BAIS, M.; BLUMTHALER, J.; GRÖBNER, G.; SECKMEYER, A.; R.WEBB; P. GORTS; T. KOSKELA; D. REMBGES; S. KAZADZIS; J.SCHREDER; P. COTTON; P. KELLY; N. KOUREMETI; K. RIKKONEN;H. STUDEMUND; R. TAX; S. WUTTKE, “Quality Assurance of Spec-tral Ultraviolet Measurements in Europe Through the Develop-ment of a Transportable Unit (QASUME)”, (2002) Proceed. SPIE,14-18 October, Shanghai, China

BRADLEY, E.; B. RAFFAEL; C. SIMONEAU, “Chemical migrationinto dry foodstuffs”, Drug, Cosmetics and Food Packaging,March 2002

BRADLEY, E.; B. RAFFAEL; C. SIMONEAU, “Migration into dryfoods”, Food Packaging Bulletin, February 2002

BRESCIA, M. A.; DI MARTINO, G.; GUILLOU, C.; RENIERO, F.;SACCO, A.; SERRA, F. “Differentiation of geographical origin ofdurum wheat semolina samplesusing isotopic composition”.Rapid Communication in Mass Spectrometry vol 16, issue 24,2002 pp 2286-2290

BRUINEN DE BRUIN, Y.; O. HÄNNINEN; P. CARRER; M. MARONI;S. KEPHALOPOULOS; G. SCOTTO-DI-MARCO; M. JANTUNEN –“Simulation of urban population exposures to carbon monoxideusing the EXPOLIS-MILAN microenvironment CO concentrationsand time activity data” (submitted to the Journal of ExposureAnalysis and Environmental Epidemiology)

BRUINEN DE BRUIN, Y.; P. CARRER; M. JANTUNEN; O. HÄNNIN-EN; G. SCOTTO DI MARCO; S. KEPHALOPOULOS; D. CAVALLO; M.MARONI – “Personal carbon monoxide exposure levels; contri-bution of local sources to exposures and micro-environmentalconcentrations in Milan” (submitted to the Journal of ExposureAnalysis and Environmental Epidemiology)

CLAUSEN,G.; E. DE OLIVEIRA FERNANDES; W. DE GIDS; C. DEL-MOTTE; S.O. HANSSEN; S. KEPHALOPOULOS; M-C. LEMAIRE; T.LINDVALL; J.F. NICOL; M. SANTAMOURIS; O. SEPPÄNEN; V. J.M.VAN DEN BOGAARD; M. WILSON; P.WOUTERS - “Ventilation,good indoor air quality and rational use of energy”, ECA reportNo. 24, 2002

DAMSTRA T. et al. (eds.) E. Marafante part of the Scientific Ex-pert group, Global Assessment of the State-of-the-Science of En-docrine Disruptors. IPCS, WHO/PCS/EDC/02.2002

Estuarine Coastal & Shelf Science – 2002, Vol 54, 355

GRÖBNER, J.; D. REMBGES; A. BAIS; M. BLUMTHALER; T. CABOT;W. JOSEFSSON; T. KOSKELA; T. MORTEN; A. WEBB; U. WESTER,“Quality assurance of reference standards from nine Europeansolar-ultraviolet monitoring laboratories” (2002), Applied Op-tics, 41, 4278-4282.

GRÖBNER, J.; A. BAIS; M. BLUMTHALER; T. CABOT; W. JOSEFS-SON; T. KOSKELA; T. MORTEN; A. WEBB; U. WESTER; D. REMBGES;(2002) “Quality assurance of reference standards from nine Eu-ropean solar UV monitoring laboratories”, 27th General Assem-bly EGS, G. Res. Abs., 4, EGS02-A-03051

KEPHALOPOULOS, S. and KOTZIAS, D. – “Towards the develop-ment of harmonizednoise prediction methods in the EU”, post-er presented in the 11th International Symposium on Environ-mental Pollution and its Impact on Life in the MediterraneanRegion, Limassol, Cyprus, October 6th to 10th, 2001

KEPHALOPOULOS, S. co-author to ARVANITIS, A., BRUNO SPOR-TISSE, Ed., Book Air Pollution Modelling and Simulation, 2002

MOULA, M.; VERDEBOUT, J. and EVA, H., “Aerosol optical thick-ness retrieval over the Atlantic Ocean using GOES imager data”,Physics and Chemistry of the Earth, 2002

MUNNS, W. R. Jr.; G. W. SUTER II; T. DAMSTRA; R. KROES; L. W.REITER; E. MARAFANTE, “Integrated risk assessment – Resultsof an international workshop”. Journal of Human and Ecologi-cal Risk Assessment, Vol.9, No.1, 2003

NERÍN, C.; J. ALBIÑANA; M. R. PHILO; L. CASTLE; B. RAFFAELand C. SIMONEAU, Evaluation Of Some Screening Methods ForThe Analysis Of Contaminants In Recycled Pet Flakes, Food Addi-tives and Contaminants, in print

NEUBAUER, G.; D. PAPAMELETIOU; T. SAMARAS; Y. HAMNERIUS;J. WIART; K. LAMEDSCHWANDNER: “Methods to Assess Exposureof the population next to mobile communications basestations”, 16th International Symposium on EMC (URSI), Maas-tricht, August 2002

PAPAMELETIOU, D. (editor): Workshop Proceedings “Risks fromchemicals released from consumer products/articles”, JRC Is-pra, June 2002

PAPAMELETIOU, D. and D. KOTZIAS: “Chemicals in Prod-ucts/Articles: Strategy for an EU framework for human exposuredata”, EUREKA Conference EURO-SUSTAIN 2002, Rhodes 2-5April 2002

PAPAMELETIOU, D.: “EMF-Risk perception and communicationissues in the EU: The Role of the JRC Collaborative Action andof the European Information System on EMF (EIS-EMF)”, Kick-off meeting of the JRC Collaborative Action on EMF, JRC, Ispra,March 1st, 2002

RAFFAEL, B., C. SIMONEAU, “Rapid screening of contaminantsfrom PET bottles by headspace GC-MS”. Journal of Chromatogra-phy (submitted)

SALIOT A.; DERIEUX S.; SADOUNI N.; BOULOUBASSI I.; FILLAUXJ.; MOMZIKOFF A.; GONDRY G.; GUILLOU C.; BREAS O.; CAUWETG.; DELIAT G., “Characterization of particulate and dissolvedorganic matter supplied by river inputs and biological process-es in the Danube delta and northwestern Black Sea mixingzone”

SIMONEAU, C.; G. ROEDER; E. ANKLAM, “Migration of BisphenolA from baby bottles: effect of experimental conditions and Eu-ropean survey”, J. Agric. Food Chem. (submitted)

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SIMONEAU, C.; A. RONCARI; P. ZOCCHI; L. FANTONI, Preparationand homogeneity testing of PVC toy materials for a European col-laborative trial study on the migration of phthalates. EUR tech-nical report EUR (in print)

SIMONEAU, C.; A. RONCARI; P. ZOCCHI; P. HANNAERT; H. GEISS,Applicability of the validated “head over heels” method to themeasurement of all phthalates plasticisers from toys consideredfor ban. EUR technical report EUR (in print)

SIMONEAU, C.; A. THEOBALD; P. RONCARI; P. HANNAERT and E.ANKLAM, “Time-temperature study of the kinetics of migrationof BADGE (bisphenol-A- Diglycidyl-Ether) into fatty medium”,Food Additives and Contaminants (2002), V19 Suppl.:73-78

SIMONEAU, C.; L. ROSSI, “Creation of on-line solutions in sup-port of the dissemination of legislative and analytical informa-tion on food contact materials”, Food Additives and Contami-nants, (2002), V19 Suppl.: 201-208

THEOBALD, A.; A. RONCARI; C. SIMONEAU and E. ANKLAM,“Identification of epoxy containing migrants from can coatingsin oil: A model study on reaction products of bisphenol-A-diglycidyl ether (BADGE) with solvents for coating production”,Deutsche Lebensmittel Rundschau (2002), V98 N7:249-256

VERDEBOUT, J. co-author to the extended UV chapter of the Ex-ecutive Summary of the WMO/UNEP Scientific Assessment ofOzone Depletion 2002. (official report for the Montreal Proto-col).

WUTTKE S.; VERDEBOUT J. and SECKMEYER G., “An improved al-gorithm for satellite-derived UV radiation.”, accepted for pub-lication in Photochemistry and Photobiology

CONTACTS

Head of UnitDimitrios KotziasTel.: +39 0332 789952Fax: +39 0332 789453Dimitrios.kotzias@jrc.it

Exposure Measurements and Risks of ChemicalsDemosthenes Papamelethiou / Dimitrios KotziasTel.: +39 0332 789952Fax: +39 0332 789453Demosthenes.Papamelethiou@jrc.it

Exposure Modelling and Environmental NoiseStylianos KephalopoulosTel.: +39 0332 789871Fax: +39 0332 785867Stylianos.kephalopoulos@jrc.it

UV Laboratory / ECUVDiana Rembges / Julian GroebnerTel.: +39 0332 785953Fax: +39 0332 785924Diana.rembges@jrc.it

ToxicogenomicsErminio Marafante / Libero ClericiTel:+39 0332 789144Fax:+39 0332 786292Erminio.marafante@jrc.it

BEVABSClaude Guillou / Fabiano RenieroTel.: +39 0332 785678Fax: +39 0332 789303Claude.guillou@jrc.it

Contact MaterialsCatherine Simoneau / Paola PiccininiTel.: +39 0332 785889Fax: +39 0332 785707Catherine.simoneau@jrc.it

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Institutional ProjectReliability of Biomedical Devices (REMED)Minimally Invasive Medical Systems (MIMES)

Some Shared Cost ActionsSTERIPLAS, LAPLADIS, MEDPHOT, BIOGRAD, ALUSI

Web information resourcesAt IHCP sitehttp://ihcp.jrc.cec.eu.int/NEW_ACTIVITIES/ACTIndex.htmlAt BMS sitehttp://bms.jrc.cec.eu.int/

bmsbmsBiomedical Materials

and Systems

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The Biomedical Materials and System (BMS) Unit deve-lops, validates and uses advanced processing techni-ques and test methodologies for the qualification ofbiocompatible materials, medical devices, and diagno-stic systems including medical applications of nucleartechnology. The above focus is based on the demandsof an ageing European population and consumer insi-stence on tools for early diagnosis and better planningof therapies. In particular, diagnostic tools that lead tothe minimization of surgery are needed for improvingpatient care and cost effectiveness of public health ca-re systems.

More specifically, the BMS activities in 2002 encompas-sed the following main priorities:

• Reliability of Biomedical Devices (REMED): Activi-ties in this priority area cover performance testing ofbiomedical devices in order to support the harmoni-zation of testing methods for material release. Thisarea also studies the performance of implant mate-rials (orthopaedic and dental) and medical devicesunder clinically relevant conditions using a combina-tion of advanced techniques (in support of Directive93/42/EEC). It focuses on functional materials andsystems, involving the development and characteri-zation of biocompatible and bioactive surfaces in or-der to improve haemocompatibility of cardiovasculargrafts, stents, catheters, and osteointegration of hipand knee replacement prostheses.

• Minimally Invasive Medical Systems (MIMES): Ac-tivities in this area apply nuclear and optical imagingtechniques to medical diagnosis and therapy. Thisinvolves, amongst other activities, the contributionto the development of standards for the distributionof radiotracers, as well as the participation in rele-vant European Networks

Both areas are of high relevance for maintaining qualityhealth services, especially in view of demographicchanges due to ageing of the population. The followingsections will discuss in more detail the aforementionedpriority areas and projects.

RELIABILITY OF BIOMEDICAL DEVICES (REMED)

Biomedical devices or implants, engineered from bio-materials, and designed to perform specific functionsnow play a major role in replacing or improving the fun-ction of every major body system and include dental im-plants and orthopaedic devices such as total knee andhip joint replacements, spinal implants or bonefixtures. From a regulatory point of view, acceptance ofa wide range of medical devices at a European Level re-quires the validation and harmonization of testing andcharacterization methods for the systems and the mate-rials used. The purpose of the project entitled“Reliability of Biomedical Devices” (REMED) is to provi-de The European Commission, in particular DG Enterpri-se and DG Health and Consumer Protection, with scien-tific and technical information related to theimprovement of standards. In 2002 the main subjectsof research were in the field of biomaterials processingand coatings, orthopaedic implant testing and advan-ced release testing methods for medical devices.

Biomaterials Processing and Coatings

Surfaces play a vital role in biology and medicine. Bio-logical reactions are frequently described as occurringin the solution phase, but in fact most reaction in bio-logy occur not in solution but at interfaces. A typicalexample of interfaces of biological importance is thecell surface/synthetic biomaterials. The advancementsin surface science characterisation and modification te-chniques together with the advances in material scien-ce and molecular biology have significantly increaseour ability to determine the surface composition andmolecular structure of biomaterials.

This will result in the development of a biological modelfor surface science to obtain a detailed understandingof the role of surface properties of a material in control-ling the biological reactivity. The challenge is to deve-lop the biological model for surface science in theextreme complex and interactive in vivo biological en-vironment.

Methods are being developed at the IHCP to study bio-filmformation on materials used in medicine. The aim of theR&D program is to develop, assess and test plasma surfacetreatment for biomedical applications. In particular, ourresearch is devoted to the deposition of carbon-based(DLC, nanocrystalline carbon, amorphous carbon nitridematerials) for prosthetic applications and on the functio-nalisation of surfaces to improve properties such as adhe-sive bonding, wettability and biocompatibility. Carbon-based coatings, such as Diamond-like carbon (DLC) and

Biomedical Materials and Systems (BMS)

carbon nitride (CNx) coatings, have received attentionin the recent years due to their hardness, wear resistan-ce and low friction coefficient. These characteristicsmake carbon-based coatings interesting for applica-tions in total joint replacement.

In 2002 the research activities focussing on the depo-sition of carbon thin films to improve mechanical pro-perties of biomaterials, especially implants and pro-sthetic devices, by means of a Plasma Assisted PhysicalVapour Deposition (PAPVD) reactor were continued. Bycoupling a microwave plasma source with two magne-tron sources diamond-like carbon (DLC) films have beendeposited with a controllable diamond character.

In 2002 the PAPVD method was also applied to depositCNx films by using a carbon solid source coupled to aDistributed Electron Cyclotron Resonance (DECR) mi-crowave plasma reactor. Optimizing the experimentalconditions, films with hardness values up to 20 GPa ha-ve been achieved. Cellular studies were carried out atECVAM, which demonstarted that the cells adhered wellto the coated support showing the typical morphologyof fibroblast growth in monolayers.

Research for improving materials biocompatibility wascarried out by means of surface grafting via plasma tre-atments. This method allows to graft aldehyde, carbo-xylic or epoxy moieties on the surface and to covalentlybond the antibodies through their amine functions. In2002 functional films were produced by plasma polyme-risation of acrylic acid (PPAA) vapour using an inducti-ve and capacitive coupled plasma sources. X-ray Photo-electron Spectroscopy (XPS) and FTIR analyses of thecoatings show that varying the process parameters (RFpower, monomer flux), can control acrylic functionsdensity on the surface and a thin film of up to 1000nmin thickness can be deposited with strong carboxyliccharacter. Moreover, wetting studies indicate the possi-bility of tailoring surface physical properties(hydrophylicity-hydrophobicity) by adjusting the pla-sma parameters. These differences in physico-chemicalsurface properties strongly influence the biological re-sponse. For example, protein (HAS) attachment kineticsis strongly dependent on the plasma parameters withthe highest amount of protein adhesion obtained atlow RF power with the most hydrophylic film.

Another key issue studied in 2002 is the functionaliza-tion of surfaces to order and organise molecules andcells. Precision immobilization aims to imitate nature’sway of organising molecules and represent an exampleof biomimetic strategy. Surface micro patterning is oneof the methods used for controlling immobilization ofbiomolecules and cells both from chemical and topo-graphic point of view. Polyethylene glycol (PEG) spincoated films have been masked and etched in a mi-crowave plasma. Subsequently PPAA has been deposi-

ted in the obtained ridges. Samples were then culturedwith endothelial CRL-1999 cells. Optical microscopyanalysis demonstrated that cells tend to group in thefunctionalised PPAA stripes.

Another research field tackled during 2002 is related tothe use plasma sources for sterilization of medical devi-ces. This research is strictly related to a SCA project(STERIPLAS), in which a plasma process is used for thedestruction of spores and pyrogens in medical devicesand polymer treatments for pharmaceutical packaging.The RF and microwave sources available at JRC have be-en tested and compared for different gas mixtures(O2/Ar, H2/Ar, O2/H2 and N2/O2). Results show thejoint effect of O radicals and UV emission from the di-scharge, on the sterilization rate of Bacillus Subtilisand a 6Log reduction can be obtained in 10 to 20 mindepending on the conditions applied. The effects onpolymers and organic thin films are used to identify dif-ferent elemental mechanisms.

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Above: Atomic Force Microscopy picture of proteins attachment on aPlasma Polymerised Acrylic Acid.Below: Atomic Force Microscopy instrument used to study nano struc-tured surfaces and protein interaction with polymers.

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Orthopaedic Implant Testing Laboratory

Between 10% and 30% of the patients, who havereceived a joint prosthesis relying on a metal-polyethylene (UHMWPE) articulation, require a revisionsurgery already after approximately 10 years due toaseptic loosening of the implant. There is strong evi-dence that this loosening is caused by the accumula-tion of submicron sized wear debris in the periprosthe-tic tissue. These particulates interact with cells, inparticular macrophages, causing a cascade of biologicalreactions. Thus, the main goal of research in improvingthe durability of orthopaedic implants is to reduce thenumber of wear debris released from the implants. Foran effective improvement of prostheses, however, har-monized test methodologies are a pre-requisite.

The IHCP Orthopaedics Implant Testing Laboratory hastherefore continued to focus its activities in 2002 onthe improvement and harmonization of wear testmethodologies in support to Directive 93/42/EEC inclu-ding methods for the characterization of wear debris bySEM and quantitative image analysis. To complete itsrange of wear test facilities a state-of-the-art 6-stationhip/knee simulator was installed, which enables the si-mulation of load and motion conditions representativefor all types of patient activities such as walking andstair climbing.

These facilities were complimented with a novel hori-zontal pin-on-disk type wear tester, which is an in-house design that provides for a rapid and cost-effective wear screening of different types of medicalgrade polyethylene materials in a short period of timeavoiding the need of long-term and expensive joint si-mulator tests. A collaboration contract with Politecnicodi Milano has been initiated on the characterization ofwear debris released from conventional and new typesof crosslinked “zero wear” ultra-high molecular weightpolyethylene (UHMWPE) articulating against CoCrMocounterfaces. Within the FP5-Shared Cost Action“ALUSI” newly developed types of wear couples consi-sting of alumina forming ferritic ODS alloys andUHMWPE were ranked according to the osteolytic po-tential of the released polyethylene wear debris. In theframe of the FP5 Shared Cost Action “BIOGRAD” scree-ning wear tests a new methodology for screening weartests of ceramic-ceramic wear couples based on theASTM 732 Reciprocating-Pin-on-Flat Test has been suc-cessfully demonstrated.

Little is quantitatively known on fretting corrosionthough recent clinical and experimental studies indica-te that modular hip joint prosthesis, artificial kneejoints and spinal fixators are prone to fretting corrosiondamage. Therefore an exploratory research project hasbeen initiated in 2002 supported through an individualMarie Curie Fellowship. It is the aim to develop a quan-titative and precise methodology for fretting corrosionstudies by combining radiotracer techniques withmechanical testing. By element-specific charged parti-cle activation the release of certain ion species can bemonitored online during fretting fatigue in body-likecorrosive media. In 2002 a newly designed testing rigto study fretting corrosion effects on metal-ion releaseof Morse taper joints in modular design hip joint pro-sthesis has been set-up. First studies will be conductedin 2003 to simulate the release from the spherical head(CoCrMo) and the stem (CoNiCrMo or Ti6Al4V).

Advanced Release Testing Methods for Medical Devices

Together with ECVAM the BMS Unit hosts the Marie CurieTraining Site BIORAD, which aims at providing high-level interdisciplinary doctoral training in testing ofbiomaterials using radiotracers. A key facility for thisTraining Site is the IHCP Biocyclotron, which is a con-cept that includes an interdisciplinary team of scienti-sts working in an infrastructure of a cyclotron, labora-tories for both the safe handling of radioisotopes andtheir use in biological and toxicological studies. Fur-thermore, it provides also training on toxicity testmethods for biomaterials, particularly metal toxicity.Apart from the Biocyclotron the Training Site provides aunique combination of facilities and expertise inclu-ding radiotracer laboratories, cell culture laboratoriesand facilities for performance testing of medical devi-ces. In 2002 the selection procedure for two studentsto start the activities in 2003 was finished.

MINIMALLY INVASIVE MEDICAL SYSTEMS (MIMES)

Minimally invasive diagnostic and therapeutic medicalmethods often have great advantages in terms of pa-tient comfort, safety, time and cost. The BMS Unit is in-volved in several aspects of development of advancedoptical systems and radioisotope techniques. These areof particular relevance in the fight against cancer.Another activity addressed within the MIMES project in2002 is an exploratory biomechanics study of bonestrength for osteoporosis research.

Radioisotope production technology

The IHCP biocyclotron allows the production of a vastvariety of radioisotopes and is best suited for researchinto the production technology of radioisotopes fornew medical applications. Radioisotopes can be usedfor labelling various kinds of molecules as biomedicalradiotracers for diagnostic and therapeutic use. Suchisotopic labelling allows the study of the functioning ofthe living body, from individual cells up to the entireorganism. The obtained information is complementaryto morphological anatomic information provided by x-ray or magnetic resonance techniques because it allowsa functional imaging of body tissue e.g. to track downcancerous metastases, to early assess response to the-rapy or to detect cardiac disorder. Radiotracer studiescan and help to understand the working of the brainand its alteration due to Alzheimer’s or Parkinson’s di-sease. Therefore, new types of radiotracers become in-creasingly important for the development and assess-ment of new therapeutic approaches.

Positron Emission Tomography (PET), the most advan-ced nuclear imaging technique, is gaining more andmore attention as a tool for diagnosis and staging ofcancer and has entered clinical practice in several Euro-pean countries. All clinically relevant applications re-quire short-lived, positron-emitting isotopes, whichcan only be produced by accelerators such as cyclo-trons. IHCP responds to these demands by collaboration

with industry and networking with other researchgroups.

The establishment of a radiopharmaceutical laboratoryfor the production of [18F] FDG (2-deoxy-2[18F]-fluoro-D-glucose) in compliance with GMP (Good Manufactu-ring Practice) standards has been completed in 2002 incollaboration with an industrial partner. Extensive te-sting of the production process and the quality controlprocedures were carried out and the conditions wereestablished for the daily “just-in-time” production of18F. The routine production of [18F] FDG will be done incollaboration with a commercial partner. The collabora-tion aims at acquiring practical knowledge in the fieldof quality control at all stages of the production processas well as on the technical and logistic issues of distri-bution and delivery of short-lived radioisotopes to ho-spitals and research organisations from a central pro-duction site. This knowledge is of strategic importance,given the lack of Europe-wide regulations for the pro-duction and distribution of short-lived PET radiophar-maceuticals, which hinders the equal access of Europe-an citizen to the best possible health care services.Moreover, the experience gained in this collaborationwill be valuable for initiatives in EU candidate states toassure supply of their population with short-lived ra-dioisotopes of high quality.

In 2002 new results have been presented on alternativeproduction routes for 64Cu. This research project is col-laboration with the Istituto Nazionale per la Fisica Nu-cleare at Milan. The scope of the project is to study anew method for the production of 64Cu, which emitsboth positrons (b+) and electrons (b-). As a b-emitter64Cu has a potential application in cancer therapy andas a positron emitter the bio-distribution of a 64Cu-labelled therapeutic molecule can simultaneously beimaged by PET. The new production route is based ondeuteron irradiation of natural Zn and Zn enriched with64Zn. The study showed also an alternative route for theproduction of 67Ga that is already used in nuclear medi-cine.

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Work on the cyclotron in July 2002 (left) and one of the fully automatic synthesis modulesfor the production of [18F] FDG (2-deoxy-2[18F]-fluoro-D-glucose) in the radio-pharmaceutical laboratory (right).

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The radioisotope 211At is a α-particle emitter with inte-resting properties for cancer therapy. Its availability ishowever limited because cyclotrons are required for itsproduction that are capable of creating a-particle beamswith high intensity and an energy of at least 28 MeV.The MC40 biocyclotron at Ispra is one of the few machi-nes with this capability in Europe. In 2002 theoreticalcalculations have been performed confirming the expe-rimental reaction cross-section data. The results showedthe necessity of new approaches in target developmentin order to achieve the theoretical yield and to enableproduction of clinically relevant batches of 211At.

Optical Methods

There is a wide variety of methods of medical diagnosisor monitoring using optical techniques. These methodsare all either non-invasive, or ‘minimally-invasive’, andseveral represent ‘frontier’ research, holding great po-tential to revolutionise medical diagnosis especially inthe area of cancer detection. The BMS has a very activegroup with considerable knowledge and expertise in thisfield, which is likely to become of great importance inmedicine and could involve future policy actions in ter-ms of regulation and standardization in this highly inno-vative area. The main thrust of the work is in developingand testing of fibre-optic based sensors for monitoringphysiological parameters such as temperature and pres-sure in clinical environments, and on the development ofendoscopic techniques for cancer detection via advan-ced fluorescence imaging spectroscopy.

The past year saw further development of Bragg-gratingand intensity-modulation fibre-optic sensors. Two JRCpatents have already resulted from this work over thepast few years and there is considerable interest fromindustrial and clinical partners to continue this deve-lopment. In fact, clinical trials of a distributed tempe-rature sensor for use in cancer therapy are planned. Thesensors may be used for in-vivo temperature or pressuremonitoring and for biochemical analysis for diagnosticpurposes. Their main advantages are that they are non-metallic (thus may be used in EM-diagnostic environ-ments such as NMR or MRI scanners), they are very bio-compatible, easily sterilised and are completely passive(i.e. require no electrical power). In addition they arestable and cheap (therefore disposable). Progress hasbeen made in refinement of the Bragg-grating writingfacility, development of numerical models for fibre-optic gratings, development of opto-electronic demo-dulation systems, a study of the feasibility of using pla-stic optical fibres rather than glass fibres, and sensorsystem prototyping. Additionally studies have been ma-de on the use of waveguides for measuring protein atta-chment on surface-modified polymers, and the use ofspectroscopic sensors for detection of micotoxins. Theformer application will form the basis of new develop-ments in the coming years.

In-vivo fluorescence-based tissue diagnosis is a techni-que that is receiving great interest and funding in manymedical research institutions. A great deal of work nee-ds to be done in terms of studying the optical characte-ristics of healthy and diseased tissue, and developingappropriate image processing techniques for clinical re-presentation. Application of the technique via endo-scopic imaging is being actively developed and manyclinical trials have been made in different research cen-tres. As a result of recent work, a JRC patent has beengranted on a particular method of endoscopic fluore-scence imaging, and further development and tests of a

A γ-spectrum of the Cu fraction after radiochemical processing of a Zntarget. The γ-peak of the 64Cu is well visible in spite of its very lowbranching ratio. The radiochemical separation procedures to eliminatethe Ga impurities are currently improved.

Experimental reaction-cross sections for the production of 211At and210At by bombarding 209Bi with α-particles

53

prototype system have been made. The endoscopic sy-stem is undergoing performance tests and optimisa-tion, and initial clinical trials are planned after the per-formance has been fully assessed using standardchromophores and cell cultures.

Biomechanical studies of calcified tissues

Osteoporosis is a disease that causes widespread suffe-ring particularly in the elderly female population, andcosts annually several billion Euro to health care systemsin the EU. Osteoporosis incidence is predicted to risedramatically over the coming decades, and yet there isstill little or no policy progress to address this issue. Atechnical assessment study of areas of expertise of theBMS Unit relevant for osteoporosis research, highlightedseveral areas, one of which was nanomechanical testingof bone matrix tissue. Bone is a highly complex material,consisting of a composite architecture of collagen,hydroxyapatite and several cell types. An enormously in-tricate channelling system allows nutrients to be distri-buted throughout the bone, and a sensing system tooperate that ensures that the bone architecture is con-stantly adapting itself to its mechanical environment.Non-invasive assessment of bone density is the main aimof current diagnostic systems for osteoporosis. These arebased on X-ray absorption or ultrasonic techniques, thebone mineral density being correlated to some extentwith bone strength. More advanced diagnostic techni-ques based on assessment of bone architecture are underdevelopment, and several research centres around theWorld are developing complex computer methods to si-mulate the mechanical response of the bone architectureto stress.

The aim of the current study is both to provide well-defined input to such models and, perhaps more impor-tantly, to assess whether the use of anti-resorptive drugshas a significant effect on the mechanical properties ofthe bone tissue. Initial tests have been made on a va-riety of animal tissues, and it is planned this year to be-gin tests on samples derived from osteoporotic and heal-thy human tissue. Complementary to these initiativesthe BMS takes part in a Consultation Panel of a EuropeanUnion Policy Project, aiming to stimulate appropriatepolicy development as regards osteoporosis. Togetherwith members of the Consultation Panel of this projectand members of the International Osteoporosis Founda-tion an initiative has been taken to set up a project ai-ming at a “fragility fracture database” in the frame ofthe DG SANCO action programme for improving HealthInformation Systems.

SELECTED PUBLICATIONS 2002

GIBSON, P.N., STAMM, H. The Use of Alloys in Prosthetic Devices.Business Briefing: Medical Device Manufacturing & Technology2002, June 2002, 48-51, World Markets Research Centre Ltd.Publs.

GIBSON, P.N. X-Ray Structural Analysis Techniques, In mono-graph: Surface and Thin Film Analysis: A Compendium of Princi-ples, Instrumentation and Applications, Edited by H. Bubert andH. Jenett, Wiley-VCH Verlag GmbH, 2002, ISBN 3-527-30458-4

WHELAN, M.P., BOUHIFD, M. Fluorescence Imaging Spectroscopyfor in vivo Diagnosis of Pancreatic Disease. Biophotonics Europe-an Workshop, FORTH-IESL, Univ. Crete, 18-19 October 2002,Heraklion, Crete (GR)

WHELAN, M.P., ALBRECHT, D.J. Principles of Optical Fibre BraggSensors and their Application in Structural Monitoring. In: Pro-ceedings of the MACSI-NET Workshop, Politecnico, 20-22 No-vember 2002, Milano (I)

NOSENZO, G., WHELAN, M.P., DALTON, T. Condition Monitoring ofVibrating Composite Structures Based on Optical Fibre StrainSensing and Finite Element Model Updating. In: Proceedings ofthe Intern. Symposium "Smart Structures and Materials", SPIE,17 - 21 March 2002, San Diego, Ca. (USA)

GARCIA-ALONSO, M.C., MACCHI, G., BRUGNONI, C. and STROOS-NIJDER, M.F.: “Electrochemical release testing of a stainlesssteel in a glucose solution using thin layer activation”, Corro-sion Science 44 (2002) 129-143.

STROOSNIJDER M.F., HOFFMANN M., SAUVAGE T., BLONDIAUX G.Wear Evaluation of Cross-linked UHMWPE by Thin Layer Activa-tion compared to Gravimetry, presented at the 28th. Society forBiomaterials Annual Meeting, Tampa, USA, April 24-27, 2002.Proceedings paper 286, Society for Biomaterials, Minneapolis,USA, 2002

R. SONNLEITNER, K. SPIRADEK-HAHN AND F. ROSSI, Microstruc-ture of plasma nitrided layers on Aluminium. Surf. and Coat.Technol. 156 (2002) 149-154

P. COLPO, T. MEZIANI, P. SAUVAGEOT, G. CECCONE, N. GIBSONAND F. ROSSI; W and WC layers deposition by shielded induc-tively coupled plasma source. J. Vac. Sci. Technol. A20(5) 20021632-1638

P. ROSSINI, P. COLPO, G. CECCONE, K.D. JANDT AND F. ROSSISurfaces engineering of polymeric films for biomedical applica-tions, Materials Science and Engineering C 1050 (2002) 1 –6

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

Minimally Invasive Medical Systems (MIMES)Neil GibsonTel.: +39 0332-785616Fax: +39 0332-785036neil.gibson@jrc.it

Uwe HolzwarthTel.: +39 0332-785194Fax: +39 0332-789385uwe.holzwarth@jrc.it

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Institutional ProjectsTelematic system for the EU pharmaceutical regulatory activity(ETOMEP)

Other Activity (through DG Enterprise)EudraNet Services

Web information resourcesAt IHCP sitehttp://ihcp.jrc.cec.eu.int/Activities/ACTPhar/ACTPhar.html

Support to Pharmaceutical Research

sprspr

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The SPR has developed several complementary informa-tion and communication systems aiming at assistingthe access to the authorised information on medicinalproducts throughout the EU regulatory authorities. Inparticular:

• The EudraNet Services supporting the cooperationfor the entire EU market and post marketing surveil-lance (Eudra = European Union Drug Regulatory Au-thorities)

• The EudraNet System supporting the marketing au-thorisation process of medicinal products throughthe mutual recognition procedure enforced by theCouncil Regulation (EEC) No. 2309/93 and by Direc-tive 2001/82/EC and Directive 2001/83/EC

Both EudraNet Services and the EudraTrack System havebeen operational since 1997. During 2002 SPR has fi-nalized the transfer of the EudraNet Services to theEMEA (European Medicinal Evaluation Agency) and hastransferred the services of the EudraTrack System to theBfArM (Bundesinstitut für Arzneimittel und Medizin-produkte, Germany) regulatory authority.

The following sections will discuss in more detail thetwo ICT systems supported by the SPR Unit in 2002.

EUDRANET SERVICES

EudraNet is a telecommunications network that hasbeen established back in 1997 to facilitate the cooper-ative regulatory process in pharmaceuticals among theEuropean Competent Authorities, the European Com-mission and the EMEA. The four objectives of theEudraNet services are:

• Enabling electronic communication and sharing ofinformation between the European Commission, theEMEA, and the national competent authorities inpharmaceuticals.

• Providing a gateway for the secure and managedcommunication over the Internet between Europeanadministrations and pharmaceutical companies.

• Hosting and providing access to Community databas-es in pharmaceuticals.

• Providing a collaborative group working environ-ment.

More specifically, EudraNet provides network services,application services (common databases) and supportservices.

The network consists of a backbone connecting dedi-cated lines of 32 organisations: the Commission, theEMEA and the national Competent authorities responsi-ble for human and veterinary medicinal products in theEU, Norway and Iceland.

In 2002 in view of the transfer to the EMEA of allEudraNet activities, including both Eudra services andthe Eudra network, the SPR undertook a major re-engineering and restructuring process to streamlineand consolidate all activities and systems necessary torun EudraNet.

The network consolidation process involved a major up-grade of all systems and the EudraMail relay servicesand included also the migration to a new ISP, in linewith the Commission framework contract. The overallsecurity of the Eudra systems was also reviewed andnew monitoring services were added to implement anIntrusion Detection System.

As part of the transfer activity, the EudraNet team inLondon, prepared a series of training sessions to facili-tate the learning process for the new team in charge ofthe EudraNet services at the EMEA in addition to a de-tailed and thorough documentation on the systems.The training sessions, which included also introductoryand tutoring components, were followed by hands-onsessions, where the systems were practically illustratedto the EMEA team.

The EMEA and the JRC signed the final EudraNet Servic-es Transfer Agreement on December 30th 2002 withwhich the EudraNet equipment, the hardware on whichthe EudraNet runs and the commercial software used toimplement Eudra services were officially transferred toEMEA.

Support to Pharmaceutical Research (SPR)

57

EUDRATRACK SYSTEM

EudraTrack is a tracking system that permits the regis-tration of procedures for marketing authorization sub-mitted through the mutual recognition process to Com-petent Authorities in the Member States of theEuropean Union. Data items relative to mutual recogni-tion procedures are introduced by the reference andconcerned Member States in a shared database that isavailable under controlled access to the EudraNet users.It provides a global picture of the ongoing proceduresand statistical reports of those already accomplished.The reshaping of EudraTrack to prepare the transfer ofthe system to a new operator was continued in 2002.On July 3rd 2002 the European Competent Authoritiesindicated to the European Commission that the new op-erator is The Federal Institute for Drugs and Medical De-vices of Germany (Bundesinstitut für Arzneimittel undMedizinprodukte, BfArM). The seven objectives of thetransfer project were:

I. Automatizing the management operations of theEudraTrack system as well as the mutual index up-loading procedure of the EudraTrack database.

II. Integrating the EudraTrack management tools andthe EudraTrack web services to the EudraTrack soft-ware application version 5.3.9.

III. Testing the new hardware and software installationtogether with BfArM and DIMDI (Deutsche Institutfür Medizinische Dokumentation und Information)before its shipment to DIMDI in September 2002.

IV. Continuing the help desk management operationand supporting the EudraTrack Sub-group chair re-quests until the system has been used as produc-tion at BfArM.

V. Uploading the data from the EudraTrack System da-tabase to the Mutual Recognition Product Index ofthe web site located in Sweden.

VI. Transferring the software source code files on onehand, and on the other hand, the data covering allprocedures between October 1997 and December13th 2002, user logins and their passwords of eachcompetent authority and the history of login crea-tion for each competent authority.

VII. Supporting fully the BfArM activities related toEudraTrack take over.

The services of the EudraTrack system were officiallytaken over by the BfArM on 16th December 2002.

SELECTED PUBLICATIONS 2002

RANA, A. - Medicine information network for Europe, Interna-tional Journal of Medical Marketing, January 2002, vol. 2, no. 2,pp. 119-124

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In January 2000 the European Commission proposedthe creation of a European Research Area (COM (2000)6). The main objective was to enhance the efficiency andinnovative impact of Europe’s research effort throughbetter integration and co-ordination of research activ-ities at a European level.

The IHCP has contributed to the implementation of aEuropean Research Area (ERA) through scientific net-working, the promotion of research training and mobil-ity, and support to EU enlargement.

NETWORKS

The IHCP sought to network with EU Member States,Accession Countries, and Association countries with aview of co-ordinating research and exchange scientificand technical information:

• European Network of GMO Laboratories (ENGL)• European thematic network on Optical Methods for Med-

ical Diagnosis and Monitoring of Diseases (MEDPHOT)• European thematic network on Innovative Plasma

Technology for Societal Needs (PLASMATECH).

FACILITIES

The IHCP has a combination of facilities that have to beset up at the EU level. Some of these facilities are:

BiocyclotronThe Biocyclotron is a highly versatile particle accelera-tor with a rather large energy range and the capabilityof accelerating protons and alpha particles (up to ener-gies of 40MeV) as well as deuterons (up to 20MeV).With this facility a wide variety of radioisotopes can beproduced, making it especially suitable for researchpurposes.

IndoortronThe Indoortron laboratory is a unique, 30m3 volumewalk-in environmental chamber featuring controlledtemperature, relative humidity, air quality, and air ex-change rate.

BEVABSBEVABS has a specialized laboratory that aims to ensurecorrect implementation of EU wine quality legislation.

RESEARCH TRAINING AND MOBILITY

The ERA promotes greater training and mobility ofyoung and senior researchers as they play an importantole in the collaboration and networking of European re-search. Within this context, the IHCP hosted 55 collab-orative staff including trainees, grant-holders (post-graduate and post-doc), visiting scientists, and sec-onded national experts.

SUPPORT TO EU ENLARGEMENT

The IHCP supports the adoption and implementation ofEU legislation (acquis communautaire) in the AccessionCountries through specialised enlargement activities(training and workshops):

• Two international workshops were organized by EC-VAM in cooperation with institutions from Polandand Hungary on the Three Rs concept in relation toanimal experimentation. The main aim of these work-shops was to provide general information on the eth-ical and regulatory framework of the Three Rs con-cept and to learn about the implementation ofDirective 86/609/EEC. In addition, the principles ofvalidation and status of alternatives in the testing ofchemicals, cosmetics, drugs, and biologicals were re-viewed by named experts from EU Member States andCCs. In addition, two smaller workshops were held inSlovenia and the Czech Republic, which focused onspecific topics, such as on alternatives to the use ofanimals in higher education and on the use of com-puter models as alternatives to animal experimentsin chemical risk assessment.

• Two grant holders from CCs joined ECVAM to work onthe development of structure-activity relationshipsfor pharmacotoxicological endpoints and on the de-velopment of in vitro testing methods for assessmentof neurotoxic and neurodegenerative potential, and ascientist from Poland was trained in a validated em-bryotoxicity test.

• BMS is a partner in an INTAS (International Associa-tion for the Promotion of Co-operation with Scien-tists from the New Independent States of the formerSoviet Union) project in the field of plasma surfacemodification techniques for biomedical materials.

Contributing to the European Research Area

Prizes/Awards

• Enrico Sabbioni (ECVAM) received the 2002 HevesyMedal award on 17th June in Antalya, Turkey, in rec-ognition of his outstanding career contribution toradioanalytical chemistry, particularly in biomedicalapplications over 40-year period. The Hevesy MedalAward is the premier international award of excel-lence to honour outstanding achievements in radio-analytical and nuclear chemistry.

• The Young scientist prize for Scientific Innovationawarded to Maurice Whelan for his work on fluores-cence spectroscopy and imaging and his developmentof a medical endoscope for the minimally invasive di-agnosis of cancer and other chronic diseases.

• Janna Puumalainen, co-ordinator of the data miningand sampling project, received the JRC Young Scien-tist Award for Environmental Research in December2002 and in addition, she received an award for theachievements in an international career by the Facul-ty of Forestry of the University of Joensuu, Finland,on the 11th October 2002.

Nominations

• Maurice Whelan was appointed to the Editorial Boardof the Int. Journal Strain.

• Prof. Michael Balls (ECVAM) was appointed the Com-mander of the Most Excellent Order of the British Em-pire (CBE) in The Queen's Birthday Honours List forhis services to humane animal research.

Patents (received by IHCP)

• Functionalization of stents with an enzyme capableof catabolizing cholesterol and lipids. EP Patent Ap-plication n.02292525.9.

• X-ray Reflectivity Apparatus and Method – a new du-al-energy method aims to resolve difficulties experi-enced with standard experimental methods, opens upthe possibility for rapid, non-destructive densitymeasurements for modified surfaces and thin films.Patent Granted n.01934187.4-2204-GB0102441.

• “Detecting and mapping of inflamed zones in a livingtissue”. A medical diagnostic technique based on im-aging fluorescence spectroscopy for the detection ofearly-stage disease such as cancer, without the needfor taking a biopsy. Patent Granted, US 6,393,315 B1(May 2002).

• “Luminous intensity sensor element and light modu-lating method and device employing such a sensorelement”. An adaptive optical device that can beused in the design of all-optical active devices, suchas actively stabilised hyper-sensitive interferometricdisplacement sensors. Patent Granted, US 6,414,782B1 (July 2002).

Training

• In 2002 two training courses on “The Analysis ofFood Samples for the Presence of Genetically Modi-fied Organisms” have been organised in collabora-tion with the Food Safety Programme within the Eu-ropean Centre for Environment and Health - RomeDivision (ECR) of the World Health Organisation. Thetraining courses are part of the collaborations be-tween the two Institutions to promote food safetyrelated issues in the WHO European Region, insideand beyond the actual EU borders, taking into specialconsideration EU Accession Countries, as well as Cen-tral and Eastern Countries with economies in transi-tion. The training courses covered the areas i) DNAextraction from raw and processed materials, ii)screening of foodstuffs for the presence of GMOs bysimple and nested PCR, iii) quantification of GMOs iningredients by real-time PCR and iv) quantification ofGMOs in ingredients by ELISA.

• Trainees came this time from Brazil, Croatia, Cuba,Cyprus, Czech Republic, Estonia, Germany, Greece,Hong Kong, Hungary, Italy, Lithuania, Poland, Portu-gal, Romania, Russia, Slovakia, Slovenia, The Nether-lands, United Kingdom, United States and Yugosla-via. In addition, The Agricultural Centre from Gödölödelegated one collaborator to both training sessionsto learn how to train. A collaboration was initiatedfor a specific training programme destined to en-largement countries. Besides the training courses,the Biotechnology & GMOs Unit has offered individu-al training for specific needs. Training in this topichas been frequently requested due to its importanceaccording to the increasing need to comply with cur-rent European legislative framework.

• The ECB organized 2 training courses regarding IU-CLID and the EU risk assessment procedures and 3IUCLID courses were successfully given to authoritiesof the member states, candidate countries and indus-try within ECB’s activities on biocides.

• Apart from 2 large conferences on recyclability andon scientific mobility the PCE contact materials labo-ratories organized one course of mathematic mode-ling.

• The BIORAD Marie Curie Training Site was granted tothe IHCP (ECVAM and BMS Biocylotron laboratories)aiming at high-level interdisciplinary doctoral train-ing on biomaterials testing using radiotracers.

• For the training program of ECVAM see section“Support to Enlargement”.

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IHCP Performance Indicators–2002

60

Competitive Activities (2002)–Examples*

* Shared-cost actions: participation in shared-cost activities with other successful consortia.

ENTRANSFOOD

Aim:

Identification of key issues of the safety evaluation ofgenetically modified food crops.

Partners:

• 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), KERKA (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)

QPCRGMOFOOD

Aim:

Development of reliable and transformation-event-specific tests for qualitative and quantitative detec-tion of genetic modifications in food.

Partners:

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

B&GMOs

NOVEL PYROGEN TESTS

Project Name: FP5 Project “Comparison and Validation ofNovel Pyrogen Tests based on the Human Fever Reaction”.

Aim:

To develop, evaluate and validate methods for the iden-tification of pyrogens (fever inducing contaminants) ininjectable drugs to replace the rabbit pyrogen test andthe Limulus assay, both part of the European Pharmaco-poeia requirements.

Partners:

• Steinbeis Transfer Centre For In Vitro Pharmacology andToxicology at the University of Konstanz (G), NIBSC(UK), PEI (G), RIVM (NL), University of Innsbruck (A),University of Bern (CH), Novartis (CH), NIPH (NO), Eu-ropean Pharmacopoeia (F)

ECVAM

61

COFAWS

Aim:

Confirmation of the origin of farmed and wild salmonand other fish.

Partners:

• Eurofins (F), Université de Nantes (F), North Atlan-tic Fisheries College (UK), SINTEF Fisheries andAquaculture (SINTEFA) (NOR)

PCE

WINE DB

Aim:

Establishing a wine data bank for analytical parame-ters for wines from third countries.

Partners:

• Bundesinstitut für gensundheitlichen Verbraucher-schutz und Veterinärmedizin (D), Department forEnvironment, Food and Rural Affairs (UK), Eurofins(F), Vrije Universiteit (B), Ministry of Finance (CZ),Agronomical University and of Veterinary Medicine‘Ion Ionescu de la Brad’ (RO), National Institute forWine Qualification (HU), Croatian Institute of Viti-culture and Enology (CR)

PICADA

Aim:

To test the photo-catalytic activity of TiO2, added todifferent building materials (concrete etc.) for itsability to induce degradation of inorganic (NO, NO2,O3) and organic compounds (VOCs).

Partners:

• Italcementi Group, Bergamo (I), University of Thes-saloniki (GR)

GLYCEROL

Aim:

To develop and test methods for detection of adulter-ation of wine by illicit addition of glycerol.

Partners:

• BfR - Bundesinstitut für Risikobewertung Berlin(D), Istituto San Michele all’Adige (I), Eurofins An-alytics - Nantes (F), Central Science Laboratory-York (UK)

MEDEO

Aim:

To develop methods based on NMR and isotopic tech-niques and tested for detection of adulteration of ol-ive oil.

Partners:

• Instituto de la Grasa (CSIC) Sevilla (E); Eurofins Ana-lytics - Nantes (F); Central Science Laboratory- York(UK); CNR - Roma (I); Istituto Elaiotecnica Pescara(I); Stazione Sperimentale degli Oli e Grassi (SSOG)- Milano (I); National Hellenic Research Athens (GR)

UVAC

Aim:

Investigation on the Influence of UVR and ClimateConditions on Fish Stocks: A Case Study of the North-east Arctic Cod.

Partners:

• Faculty of Fisheries and Natural Sciences, Bodø Col-lege (NOR); Technological Institute for Fisheriesand Food, San Sebastián (E); Norwegian College ofFisheries Science, University of Tromsø (N); Norwe-gian Institute for Air Research, Tromsø (N); GermanAerospace Center, Institute of Atmospheric Physi-ca, Oberpfaffenhofen (D); Institute of Marine Sci-ence, Vigo (E)

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FOODMIGROSURE

Aim:

To develop physico-chemical migration models of mi-gration processes from plastics to real foodstuffs as atool for estimation of consumer exposure from foodcontact materials.

Partners:

• Fraunhofer Institute of Process Engineering andPackaging, Freising (D), Central Science Laboratory,Dep. Food Environment & Rural Affairs, York (UK);FABES Forschungs GmbH für Analytik und Bewer-tung von Stoffübergängen (D); Pira International,Leatherhead (UK); University Santiago de Compost-ela, Dpto. Química Analitica, Nutrición y Broma-tología of the Facultad de Farmacia (ES); ViennaUniversity of Technology, Inst. Food Chemistry andFood Technology (A); Nestlé Research Center,Lausanne (CH); European Chemical Council; Bu-reaux International aux Techniques (BE)

EIS-EMF

Aim:

To set up a European Information System on publichealth protection issues related to Electromagneticfields (EIS-EMF) as a common basis for decision mak-ers to increase the coherence of the approaches takenin the various Member States and help restore publicconfidence.

Partner:

• Research Centre Seibersdorf (A)

HARMONOISE

Aim:

To develop methods by which the sound power out-put and the directivity of sources of road and railtraffic can be described and assessed as an accuratephysical quantity which is independent of short dis-tance sound propagation, including establishment ofa correlation with future legislation on limiting thenoise generation, set up of data base.

Partners:

• AEA Technology Rail BV (SP), Swedish NationalTesting and Research Institute; Transport ResearchLaboratory (UK); VTI, Swedish Road and TransportResearch Institute; Technical University of Gdansk,Autostrade (I).; TNO Institute of Applied Physics(NL) (non-exhaustive list)

INDEX

Aim:

To create a network of European scientists in the areaof indoor air pollution and the herewith-associatedhealth impacts.

Partners:

• Federal Environmental Agency Germany (UBA), Na-tional Institute for Health (KTL Kuopio, FIN), Uni-versity of Aarhus (DK) (non-exhaustive list).

GC-IRMS

Aim:

Feasibility study for establishment of reference mate-rials for the gas chromatography isotopic ratio massspectrometry.

Partners:

• Eurofins Analytics - Nantes (F), Central Science Lab-oratory- York (UK), INETI - Lisboa (P)

SPREADS

Aim:

To study NMR measurements for detection of adulter-ation of spreadable fats.

Partners:

• Universität für Bodenkultur (A), Bundesanstalt furMilchforschung (D), Unilever Nederland BV (NL),Mylnefield Research Services LTD (UK)

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QASUME

Aim:

The development of a new approach for facilitatingQuality Assurance of solar ultraviolet spectral irradi-ance measurements presently carried out in Europe.In this frame a transportable Unit, developed andhosted at the PCE Unit, which, after thorough testingand validation, will be visiting European UV stationsto acquire spectral measurements of global solar irra-diance that will be compared with those of the localspectroradiometers

Partners:

• Laboratory of Atmospheric Physics, Aristotle Uni-versity of Thessaloniki (GR), University of Inns-bruck (A), University of Manchester Institute ofScience & Technology (UK), Institute for Meteoro-logy and Climatology, University of Hannover (D),National Institute for Public Health and the Envi-ronment (RIVM) (NL), Finnish Meteorological Insti-tute (FIN).

EDUCE

Aim:

To investigate the ultraviolet (UV) radiation climatein Europe.

Partners:

• Institute for Meteorology and Climatology, Univer-sity of Hannover (D); Norwegian University of Sci-ence and Technology; Institute for Geophysics, As-trophysics and Meteorology, University of Graz (A);Finnish Meteorological Institute; British AntarcticSurvey; Laboratory of Atmospheric Physics, Aristo-tle University of Thessaloniki (GR); National Insti-tute of Public Health and the Environment (NL);University of Manchester Institute of Science &Technology (UK); University of Innsbruck (A); Solarand Ozone Observatory - Czech Hydrometeorologi-cal Institute (CZ); Institute of Geophysics - PolishAcademy of Sciences (PL); Tartu Observatory (Esto-nia); (non-exhaustive list)

BMS

BIOGRAD

Aim:

Increasing the performance of total hip replacementprostheses through high functionally graded mate-rial innovation and design.

Partners:

• Lima Lto (I), Ceramtec (D), HIP Bodycote (UK)• University of Leuven (B), Helsinki University of

Technology (FI), LEMI (F), Josef Stefan Institute(SLO), Nuclear Physics Institute (CZ)

EVIGeM (virtual Institute)

Aim:

The European Virtual Institute of Geometry Measure-ment (EVIGeM) consists of a linked group of Europeanpartners, committed to assists and help members andany external customer on all kind of problems con-cerning geometry measurements.

Partners:

• BIBA (D), Knapp (CH), Mahr (D), Unimetrik (E)

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SPOTS

Aim:

Standardisation Project for Optical Techniques of StrainMeasurement.

Partners:

• University of Sheffield (UK), Optical Metrology Inno-vations (IRL), Ettemeyer AG (D), NPL ManagementLtd (UK), SNECMA Moteurs (F), Honlet Optical Sys-tems GMBH (D), Politechnika Warszawska (PL), CRFSocietà Consortile per Azioni (I), Eidgenössische Ma-terialprüfungs- und Forschungsanstalt (CH)

MEDPHOT

Aim:

Use of optical Methods for Medical Diagnosis andmonitoring of diseases.

Partners:

• ISIS OPTRONICS GmbH (D), R. Wolf GmbH, STORZ(D)

• FORTH-ISEL (GR), PTB-National Metrology Instituteof Germany, Lund Laser Centre (D)

• ILM-University of Ulm, Robert-Rossle Hospital-Berlin, Humboldt University, MLL-University,Lubeck (F), Storz (D)

• University L’Aquila (I), Univerity of Paris XIII (F), Uni-versity of Twente (NL)

• AMC, Laser Centre (NL), Politecnico di Milano-POLIMI (I), Academisch Ziekenhuis Rotterdam(NL), ICSTM- Imperial College (UK)

ALUSI

Aim:

Development of alumina forming ODS ferritic superal-loys as new biomaterials for surgical implants.

Partners:

• Consejo Superior de Investigaciones Científicas(CSIC.CENIM) (SP), Asociación Instituto de Bio-mecánica de Valencia (SP), Istituto Ortopedico Riz-zoli (I), Technische Universität Clausthal (D), Sur-gival (SP), Metallwerk Plansee GmbH (G)

STERIPLAS

Aim:

Study and validation of an advance plasma sterilisa-tion process.

Partners:

• ARJO WIGGINS (F), R BOSCH GmbH (D), METAL PRO-CESS (F), BIOMATECH S.A. (F), C.I.R.M. (I)

LAPLADIS

Aim:

Large Area Plasma Etching Process for Display Appli-cations.

Partners:

• FIAT (I), THOMSOM (F), FHR (D), EUROINKS (I)

IFCA

Aim:

Immunoprobes for Food Contamination Analysis (IFCA).

Partners:

• École Nationale Supérieure de Chimie de Paris (F),Universidad de Vigo (E), Innosense SpA (I), LCC(CH), Abkem (ES), CSMA (UK)

European Commission

EUR Report 20660 EN – Institute for Health and Consumer Protection (IHCP) – Activity Report 2002Editor: Michael HoffmannLuxembourg: Office for Official Publications of the European Communities2003 – 64 pp. – 21.0 x 29.7 cmScientific and Technical Research seriesISBN 92-894-5312-5

JRC and the IHCPhttp://www.jrc.org/

The Joint Research Centre (JRC) is a Directorate General (DG) of the European Commission. It has its headquarters inBrussels and seven institutes located in five separate sites:

• Institute for Reference Materials and Measurements (IRMM) — Geel, Belgium• Institute for Transuranium Elements (ITU) — Karlsruhe, Germany• Institute for Energy (IE) — Petten, The Netherlands• Institute for Prospective Technological Studies (IPTS) — Seville, Spain

The largest site is located in Ispra, Italy, hosting three institutes:• Institute for Health and Consumer Protection (IHCP)• Institute for Environment and Sustainability (IES)• Institute for the Protection and Security of the Citizen (IPSC)

PETTEN

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The mission of the Joint Research Centre is to provide customer-driven scientific and technical support for the con-ception, development, implementation and monitoring of European Union policies. As a service of the EuropeanCommission, the JRC functions as a reference centre of science and technology for the Community. Close to thepolicy-making process, it serves the common interest of the Member States, while being independent of commer-cial or national interests.

EUROPEAN COMMISSIONJOINT RESEARCH CENTRE