1. Children in Their Environments: Vulnerable, Valuable & at Risk EEA, WHO Europe & the Collegium Ramazzini workshop June 22nd, 2004 Biomonitoring, towards more integrated approaches Dr. Ludwine Casteleyn Chair TWG Biomonitoring of Children Ministry of the Flemish Community AMINAL

2. TWG Biomonitoring for Children Bloemen Louis, Brits Ethel, Boogaard Peter, Canna Michaelidou Stella, Fréry Nadine, Fucic Aleksandra, Harrison Paul, Jakubowski Marek, Lehners Maryse, Lorente Christine, Ramet José, Seifert Bernd, Schoeters Greet, Steenhout Anne, Ten Tusscher Gavin W., Wattiez Catherine, van Wijnen Joop Co Chairs: Sala Carlo, Knudsen Lisbeth E., Chair: Casteleyn Ludwine Assisted by: Joas Reinhard, Bauer Sonja Commission: Van Tongelen Birgit.

3. 3 Human Biomonitoring = measuring in humans (effect) of exposure air water soil food consumables “Monitoring activities in children, using biomarkers, that focus on environmental exposures, diseases and/or disorders and genetic susceptibility, and their potential relationships”.

4. Biomarkers http://www.milieu-en-gezondheid.be 2001-2006

5. 5 Flemish Health and Environment Study Pilot study (1999) zTest feasibility, assess relevance (small scale study) z“whether residence in areas with different pollution pressure has a significant impact on internal exposure to pollutants and resulted in adverse biological effects” z2 industrial suburbs of Antwerp: yWilrijk: 2 waste incinerators yHoboken: large non-ferrous smelter- known lead pollution z1 rural municipality: Peer (“control area” - measured environmental pollution low) http://www.wvc.vlaanderen.be/gezondmilieu/ Koppen et al, 2001 Toxicology Letters, 123, 59-67 Koppen et al, 2002, Chemosphere, 48, 811-852 Nawrot et al, 2002, Env Health Perspectives, 110, 583-589 Staessen et al, 2001, Lancet, 357,1660-1669

6. 6 0 0.25 0.5 0.75 1 Peer WilrijkHoboken µg/L adolescents women ** Pilot study Cadmium blood

7. 7 0 0.05 0.1 Peer Wilrijk Hoboken µg/g creatinine adolescents women * * Pilot study 1-OH pyreen urine 0.15

8. 8 Pilot study Marker PCBs serum 0 100 200 300 400 500 PeerWilrijkHobokenNederland (gem. 29j) ('90-'92) Zweden (gem. 42j) ('86-'91) ng/g vet adolescents women * *

9. 9 Pilot study Dioxine-like substances 0 5 10 15 20 25 30 35 40 45 50 PeerWilrijkHobokenBelgian women gem.32 j ('96-’98) pg TEQ/ g vet adolescents women * *

10. 10 Pilot study: Women: HPRT mutant-frequency 0 1 2 3 4 5 6 7 8 9 10 PeerWilrijkHoboken number/million cells normal range * Van Larebeke et al, Biomarkers, vol. 9, no 1, 2004, 71-84

11. 11 Pilot study Men: Sperm + testosterone 360 380 400 420 440 460 480 PeerWilrijkHoboken ng/dL testosterone 0 2 4 6 8 10 12 14 16 18 20 % normal testosterone blood morphology sperm N O R M A A L OK * *

12. Pilot study Adolescents: sexual maturation

13. 13 Pilot study: conclusions zgeographical differences & individual differences zadolescents and adults: geographical differences not following same trends zdespite low measured environmental pollution ‘Peer’ not always reference area zfindings suggest that current environmental standards are insufficient to avoid measurable biological effects z...

14. 14 Flemish biomonitoring program for surveillance of environmental health Flemish Institute for Technological Research (VITO), Belgium Greet Schoeters et al

15. 15 Goals zAnalyse time trends : efficacity of environmental measures for public health zAnalyse spatial trends : healthy and unhealthy areas zDetect yet unknown environmental threaths: early warning system for unknown pollution sources / pollutants

16. 16 Legal framework (B.S. 03-02-2004) Preventiedecreet Art 51 § 1 The Flemish government: 1. can set up a network for surveillance of exposure (measured in humans) and/or effects of exposure to physical and chemical factors in the population, with the intention to take measures to protect public health. 2.takes at least measures for the development and execution of a program for biomonitoring. 3. can - in execution of &1 - set up a fund (…). For this purpose a mandatory financial contribution can be imposed on industries or citizens that are responsible for the presence of physical or chemical factors harmful to health.

17. 17 ztotal number of questionnaires received: 97 zreported budget with 47 questionnaires: about 57 million euro zabout 480 000 children are covered (basis 90 questionnaires) z42 covered heavy metals, z25 projects examined asthma or allergies z19 projects covered dioxin/PCB exposure, z4 covered endocrine disrupters … generally not carried out using the same methodological approach. Human biomonitoring studies related to children in European countries difficult to compare the data generated

18. 18 A substantial amount of biomarker data is collected zaddressing simultaneously markers of exposure, effect and susceptibility and also additional data on environmental factors and health zaddressing both children and their parents (particularly their mothers, therefore integrating prenatal and postnatal exposure) z Integrating: various routes of exposure various sources of past and recent exposure Biomonitoring = Integration

19. 19 2 types of biomarker activities zSURVEY projects: activities that aim at periodical measurements in order to produce information on the prevalence of exposure to environmental agents and the related public health impact with a view to developing and evaluating policies that protect health zRESEARCH projects: activities that aim at improvement of knowledge on causal links between environmental factors and health by hypothesis generation and testing

20. to generate representative data on the concentration distribution of environmental pollutants in media like air, water, soil, dust, food, and in human specimens, such as blood or urine; to establish reference values based on these distributions; to document and interpret spatial and temporal differences in population exposure; to provide policy makers with information if and what measures should be taken. Objectives of the German Environmental Surveys (GerES) to get insight into the contribution of different compartments (air, water, food) to the body burden; B. Seifert, K. Becker, C. Schulz, C. Krause Federal Environmental Agency, Germany

21. 21 zRecruitment of study population Biological samples such as blood and urine are difficult to obtain especially in children less invasive sampling techniques /financial incentives zBiomarkers validation of biomarkers is incomplete zLogistics biomonitoring is a time consuming effort y sufficient staff is not always available y high investment of medical staff is needed y continued funding of long term studies is problematic Problems and deficits

22. 22 Communication zto the participants/public: what and how to communicate when the links with health risks, especially at the individual level, are not well defined zto the authorities: reporting to the relevant authorities is often lacking zgood communication is crucial and an active involvement of professionals in the field is needed Problems and deficits

23. 23 zEthical issues need special attention since sensitive information may be derived from biomonitoring and the child is not able to consent. Issues of confidentiality and data protection should have special attention as well as opportunities of opting out later when mature (18 years of age) see report of meeting in Copenhagen 5-7th Dec www.pubhealth.ku.dk/cgn Ethics

24. 24 A more harmonised biomonitoring approach zComparability would contribute to the EU Strategy for E & H by: yProviding data on distribution of exposure and related health impact across Europe definition of reference values detection of spatial differences in exposure (populations/regions at risk) detection of temporal differences in exposure yProviding policy makers with better information on control measures to be taken identification of priorities in exposure reduction strategies allowing follow up of the efficiency of reduction strategies, allowing a geographically differentiated E&H policy

25. 25 A more harmonised EU biomonitoring approach zEnable a more effective use of resources by shared development of tools and strategies zEnable more meaningful results of national surveys as the number of study subjects involved becomes larger  Allow for a more equal distribution of efforts amongst European countries and a better respecting of the equal right of each European citizen on healthy environments.

26. 26 Action Plan Approach: Step-by-Step Strategy I Develop guidelines for a harmonised EU approach for biomonitoring II Start an European wide pilot project III Develop tools to translate results into a response system http://www.brussels-conference.org/Download/baseline_report/BR_Biomonitoring_final.pdf http://europa.eu.int/comm/environment/health/pdf/040330biomonitoring.pdf

27. 27 I. DEVELOP GUIDELINES Develop technical guidelines for common use with the aim of harmonising The guidelines should address issues related to initiation, performance and follow up of biomonitoring activities: Design and protocol for surveys Sampling strategy and analysis Data treatment Dissemination and information of results Ethical rules and practices, social and legal aspects

28. 28 II. START EU WIDE PILOT PROJECT z“Learning by doing” tool zTest and validate common harmonised approaches for all steps zFacilitate the establishment of collaboration networks and the sharing of methodologies zPromote the idea of harmonisation in biomonitoring. zIdentify possible problems linked with such harmonisation

29. 29 II. START EU WIDE PILOT PROJECT zIn view of not complicating the study by major analytical problems it is proposed to select a pollutant: yfor which there is already sufficient analytical experience. yfor which the exposure and health relevance is well known zPossible candidates: lead and mercury yin line with a WHO proposal to ensure regular biomonitoring of lead (amongst other hazardous chemicals) in at risk children. lead and mercury

30. 30 III Translate results into a response system zDevelop scenarios for translation of biomonitoring data into a response system. Such scenarios require yintegration of biological monitoring data with environmental monitoring and health data ythe development of xreference values to which biomarker results from different areas or time periods can be compared xhealth based action levels that can help indicate when measures need to be taken in order to reduce body burden for most exposure- and effect biomarkers NO health based values exist Child-specific

31. 31 zIn order to translate the results of biomonitoring into policy measures, effective communication is needed. zEffective communication needs participation and exchange between the different stakeholders (general public, study participants, general practitioners, regulators, scientists, public interest NGO’s, industry, others) and will promote public awareness. zA communication plan is an essential part of a biomonitoring programme and should be a part of the study design. III: Translate results into a response system

32. 32 HOW ? Establish specific working group(s) zBringing together existing expertise and experiences yFrom MS already carrying out surveillance programmes yFrom occupational health field yFrom research field zAim: to develop yharmonised technical procedures ya protocol for carrying out a pilot project ytools allowing for translation of biomarker results into intervention strategies zIn coordination with Commission and MS

33. 33 Integration of environment and health zHuman biomonitoring is an excellent tool to better integrate the two fields, environment and health zOne of its big advantages is that within the chain it is much closer to health effects than environmental monitoring Biomarker of susceptibility Biomarkers of exposure Internal dose Biological effective dose Biomarker of effect Early response Altered structure and funcion Disorder Disease ExposureEmission Ambient level

34. 34 to measure is to know … the pitfalls lay in who’s to read and how? for proper policy making: interpretation - by experts - in combination with other data - respons - prevention and precaution - communication