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Deel 3: Meerjarenprogramma en begroting

Part 3: Multi annual program and budget

Verplicht op te stellen in het Engels (de begroting in het Nederlands)

Steunpunt Milieu en Gezondheid

4de generatie

2016-2020

Promotor coordinator: Prof. Dr. Greet Schoeters (VITO and UAntwerpen)

Promotor on behalf of the initiator: Prof. Dr. Ilse Loots (UAntwerpen)

Acroniem van het voorstel – Acronym of the proposal:

STP MG – FLEHS IV

(Dit deel vormt een apart digitaal bestand)

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Table of Contents

1. Introduction ________________________________________________________________ 6

General Aims ________________________________________________________________ 6 Background _________________________________________________________________ 6 Concept of the new program ___________________________________________________ 7 The consortium _____________________________________________________________ 10

2. Description of the work packages ______________________________________________ 12

PILLAR 1 13

WP1: Coordination 13 Objectives _________________________________________________________________ 13 Approach __________________________________________________________________ 13 Deliverables ________________________________________________________________ 14 Partners ___________________________________________________________________ 14

PILLAR 2: SCIENCE-POLICY INTERFACE AND RISK COMMUNICATION 16 Background ________________________________________________________________ 16

WP2.1: Cross-cutting (policy) consultation on HBM 19 Background ________________________________________________________________ 19 Objectives _________________________________________________________________ 19 Approach __________________________________________________________________ 20 Deliverables: (M12) __________________________________________________________ 21 Partners ___________________________________________________________________ 21

WP 2.2: Science – policy translation (‘phased action plan’) 22 Background ________________________________________________________________ 22 Objectives _________________________________________________________________ 23 Approach __________________________________________________________________ 23 Deliverables ________________________________________________________________ 25 Partners ___________________________________________________________________ 25

WP 2.3: Risk communication and social inclusion 26 Background ________________________________________________________________ 26 Objectives _________________________________________________________________ 28 Approach __________________________________________________________________ 28 Deliverables ________________________________________________________________ 32 Partners ___________________________________________________________________ 32

PILLAR 3: HUMAN BIOMONITORING PLATFORM 33 Background ________________________________________________________________ 33

WP 3.1 : Study design 35 Background ________________________________________________________________ 35 Objective __________________________________________________________________ 35 Approach __________________________________________________________________ 35 Deliverables ________________________________________________________________ 36 Partners ___________________________________________________________________ 36

WP3.2 Questionnaires 37

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Background and objectives ____________________________________________________ 37 Approach __________________________________________________________________ 37 Deliverables ________________________________________________________________ 37 Partners ___________________________________________________________________ 37

WP3.3 Recruitment and sampling 38 Background ________________________________________________________________ 38 Objectives _________________________________________________________________ 38 Approach __________________________________________________________________ 38 Deliverables ________________________________________________________________ 39 Partners ___________________________________________________________________ 39

WP3.4 Toxicological analysis 40 Background ________________________________________________________________ 40 Approach __________________________________________________________________ 40 Deliverables ________________________________________________________________ 43 Partners ___________________________________________________________________ 43

WP3.5 Construction of database and data analysis 44 Background ________________________________________________________________ 44 Objectives _________________________________________________________________ 44 Approach __________________________________________________________________ 44 Deliverables ________________________________________________________________ 45 Partners ___________________________________________________________________ 45

WP3.6 Biobanking 46 Background ________________________________________________________________ 46 Objectives _________________________________________________________________ 46 Approach __________________________________________________________________ 46 Deliverables ________________________________________________________________ 46 Partners ___________________________________________________________________ 46

WP3.7 Reporting 47 Objectives _________________________________________________________________ 47 Approach __________________________________________________________________ 47 Deliverables ________________________________________________________________ 48 Partners ___________________________________________________________________ 48

PILLAR 4: EXTERNAL EXPOSURE AND HEALTH 49

WP4.1 Space and health 49 Background ________________________________________________________________ 49 Objectives _________________________________________________________________ 50 Approach __________________________________________________________________ 50 Deliverables ________________________________________________________________ 51 Partners ___________________________________________________________________ 51

WP4.2 Eco-behaviour and exposure 52 Background ________________________________________________________________ 52 Objectives _________________________________________________________________ 53 Approach __________________________________________________________________ 53 Deliverables ________________________________________________________________ 54

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Partners ___________________________________________________________________ 54

WP4.3 Follow up studies 55 Background ________________________________________________________________ 55 Objectives _________________________________________________________________ 55 Approach __________________________________________________________________ 55 Deliverables ________________________________________________________________ 56 Partners ___________________________________________________________________ 56

WP4.4 Emerging chemicals 57 Background ________________________________________________________________ 57 Objectives _________________________________________________________________ 57 Aproach ___________________________________________________________________ 57 Deliverables ________________________________________________________________ 59 Partners ___________________________________________________________________ 59

3. Time tables 2016-2020 (personeelsinzet per WP to be included) _____________________ 60

4. Gantt Chart ________________________________________________________________ 61

5. Unlocking Knowledge ________________________________________________________ 62

External information and communication 62 Public communication________________________________________________________ 62 Publications and active distribution of information to a broad public ___________________ 63 Authorship of publications ____________________________________________________ 63

Foreground Knowledge - Ownership and User Rights 64

6. Interaction with the Flemish authorities _________________________________________ 65

7. Quality Assurance ___________________________________________________________ 66

8. Budget ____________________________________________________________________ 68

Global budget per partner ____________________________________________________ 68 Global budget per cost category ________________________________________________ 69

9. References ________________________________________________________________ 70

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1. INTRODUCTION

GENERAL AIMS

This 5 year proposal (2016-2020) aims to establish the Flemish Center of Expertise on Environment and Health of the fourth cycle which will be a scientific knowledge pool for environmental health in Flanders. The gained knowledge aims to improve environmental health and wellbeing by quantifying the effects of environmental determinants on public health with special emphasis on vulnerable populations. The center will build on the strengths and experience gained in the first three cycles of the Flemish Center of Expertise on Environment and Health 2001-2006, 2007-2011, 2012-2015 and will address new upcoming challenges. The Center will develop annual work plans that will allow further steering based on new insights and new demands. These plans will be submitted to the steering group for approval.

BACKGROUND

Flanders is situated at the cross roads of Europe, it is a highly dynamic and industrialized region with a high population density. The objectives of the Flemish authorities are to provide a high level of environmental protection for current and future generations by taking care and making the best use of the sparse and precious environment. The protection of the quality of the environmental compartments and the promotion of healthy lifestyles are drivers towards a healthy population within a sustainable society. Recent calculations value the toll of air pollutants and nuisances in Flanders at the loss of 1 year of life per inhabitant on average [1]. Recent human biomonitoring (HBM) data have shown decreasing levels of specific heavy metals and persistent organic pollutants during the course of the biomonitoring cycles since 2002. Based on these human biomonitoring data we estimated that decreasing lead levels, thanks to appropriate measures and environmental hygiene, improve intellectual capacity of the Flemish population with 16661 IQ points, which is the equivalent of an economic benefit of 274,22 million Euro (Remy et al, unpublished results). Despite these positive trends, we encounter a large number of new chemicals that pop up in the environment due to new products that are being developed, reuse of materials and products and new lifestyles. Public authorities offer guidance towards healthy environments and lifestyles. The current proposal wants to support the policies of these public authorities based on solid scientific knowledge. It aims to give guidance to opportunities for prevention-oriented improvement in policy and practice. The human biomonitoring program of the Flemish Center of Expertise on Environment and Health investigates the very complex relation between environmental pollution and human health by measuring selected pollutants and certain health effects in humans, using biomarkers. Human biomonitoring is one of the most direct methods to measure the impact of pollutants in men [2]. Biomarkers of exposure and biomarkers of effect will be monitored. The first type of biomarkers gives information on exposure over time by various routes and also on the resulting internal dose. For a limited number of pollutants the internal dose can be compared to international standards such as the HBM values developed by the German HBM Commission [3] and biomonitoring equivalents [4] by Summit Toxicology. The second type of biomarkers, the effect biomarkers, allows measuring biological

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and health effects due to environmental exposure in an integrative way, including the effect of unidentified substances and taking antagonistic and synergetic effects into account [5]. Since 2002 a human biomonitoring network has been established in Flanders (Belgium) as part of a program on environmental health surveillance [6]. The first Flemish Environment and Health Study (FLEHS I 2002-2006) “monitoring for action” included more than 4,400 participants recruited from 8 regions in Flanders with different environmental characteristics. The participants were recruited by a stratified clustered multi-stage design and belonged to 3 different age groups (newborns and their mothers, 14-15 yrs. old adolescents and 50-65 yrs. adults). The first cycle of the HBM evaluated exposure to traditional pollutants such as cadmium, lead, dioxin-like compounds, hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), para-,para-dichlorodiphenyldichloro-ethylene (p,p’-DDE), polyaromatic hydrocarbons (PAH’s) and benzene and showed that living in areas with different environmental pressure yields a different fingerprint of pollutants in the body indicating the importance of region based environmental policies and priorities [7,8]. The possibility to obtain geographically differentiated information on environmental health was exploited further in the second cycle of the human biomonitoring program (FLEHS II 2007-2011). A participatory process was used to propose and finally select 2 hot spots of interest for human biomonitoring [9]. The hypothesis was tested whether in the hot spot areas specific biomonitoring data (exposure and effects) are different from reference values that have been obtained over Flanders. As part of the second cycle of the biomonitoring program we obtained reference data for a much wider set of exposure biomarkers compared to the first cycle, this was emphasized by the slogan “What are you carrying with you?” Reference values for more than 50 biomarkers were generated [10]. The third cycle of the program has allowed to generate time trends of internal pollutant levels in humans of the general population of Flanders. The program has also allowed to evaluate the associations between exposure levels and different health outcomes in prospective cohorts of the first two cycles of the Flemish environmental health surveys (FLEHSI and FLEHSII) [11,12]. In addition we have used the HBM data to estimate the positive effects on health as we have seen decreases in biomarker levels of specific metals and persistent organic pollutants over time. However FLEHS III has also shown that for some chemicals no decreasing time trends can be observed yet. Many other chemicals that emerge from new lifestyles and habits have never been investigated. Besides, we demonstrated that levels of environmental exposures are related to differences in socio-economic status (SES) of the study participants emphasizing inequity of exposures and presumably also in health risks [13]. The need for targeted environmental protection guidance for subgroups in the population in relation to lifestyle and SES related is warranted.

CONCEPT OF THE NEW PROGRAM

The human biomonitoring platform: The core activity of this proposal is to establish a biomonitoring program in line with the Decree on Preventive Health Care voted in 2003 in Flanders that supports environmental health policies in Flanders. This biomonitoring program is a framework that collects data on human environmental exposures as well as human biological samples that will be collected in a biobank and may serve for future investigations of time and life style exposure trends as well as early warning markers of exposure and disease. By analyzing the samples, the program watches time trends of human exposure to toxic chemicals as they are being regulated. The program serves also as an early warning instrument for upcoming new chemicals that are introduced in the environment and to which humans are exposed. This important data set will be made available and used for policy supporting analysis and interpretations. We will aim for maximal transparency with respect for ethical and privacy issues. We will establish clear communication rules within the consortium and towards participants of the human biomonitoring program and stakeholders.

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The scientific research activities of the center will make use of the human biomonitoring dataset and will connect these data to environment and health data and information. The program 2016-2020 will address specific research questions that relate to selected themes that are transversal throughout the program. Research questions of the new program: As society changes, new insights and approaches are needed. This proposal builds on previous knowledge but the consortium has also identified new cross-cutting issues which will be touched upon in all scientific pillars and work packages.

1. Use of open space and health The open space is limited in Flanders. More people are living in cities. Cities are changing and are increasingly investing in green and blue infrastructures. Also in more rural areas the open space is reorganized. We will investigate to what extent the proximity and accessibility of green, blue, grey infrastructures and agricultural areas may have impact on the internal chemical load and on biological parameters that are related to health outcomes.

2. Eco-behaviour: healthy consumers and energy-efficient housing Healthy lifestyles are promoted. These may include use of organic food, home farming, the use of ecological products for cleaning etc. It is anticipated that these so called “eco-behaviours” reduce the personal burden of toxic chemicals and have a positive impact on health. Human exposure and effect monitoring will give further guidance healthy consumers. Another aspect that is associated with eco-behaviour is that individuals apply new building techniques in search of energy efficiency. Passive houses and low energy houses are becoming very popular. New materials and new air ventilation systems are being used, air circulation is different and may have impact on the indoor air quality and on internal human exposure. We will investigate the impact on human exposure of different building environments by selecting specific human exposure biomarkers related to indoor air quality.

3. Emerging chemicals New chemicals are continuously introduced in our environment and humans are exposed to a changing spectrum of chemicals. These new chemicals are often substitutes for toxic persistent chemicals and are in general less persistent. However, in many cases, the toxicity of these new chemicals has not been sufficiently investigated. Also, it is a continuous challenge to trace these chemicals in the human body. We will focus on the emerging chemicals that relate to the topics mentioned above. Research will include optimization of the biomarker analysis, selection of the appropriate matrix and interpretation of the determinants of exposure. New approaches:

1. Science policy interface: involving (policy) sectors from the beginning The social and policy relevance of the previous human biomonitoring campaigns of the center was enforced by a participatory procedure to interpret and prioritize the study results for policy goals. This systematic and stepwise approach was developed and successfully experimented as a co-production between the center and the environment and health administrations in FLESH I, and has been incorporated in the research practice since then. Additionally, a few ad-hoc initiatives were organised to improve policy relevance by the start of new research campaigns (ex-ante), e.g. to select the most appropriate hot spots for HBM in FLESH II and to prioritise biomarkers in FLESH III.

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In the new cycle of the center, this ex-ante consultation will be structurally embedded, as is already the case for the ex-post interpretation. Moreover, the new cross-cutting themes in this project proposal require an expansion of the policy domains and stakeholders involved, compared to previous consultation processes. Such as spatial planning and infrastructure, housing, youth policy, agriculture, product policy and social inclusion. A dialogue on the relevant environmental health knowledge with these adjacent policy fields and their framing of the environmental health issues will be set up. This allows the interweaving of environmental aspects in other policy domains and vice versa, specific concerns with regard to environmental health from other policy fields can be taken into account and included in the study. In return we expect to increase awareness and support from other sectors for dealing and taking care of environmental impacts and improve opportunities for policy integration.

2. Adolescents as the target study population In order to have enough study power we will focus on one age group namely adolescents. This will simplify the recruitment. We will increase the sample size which will allow to investigate more variables on the same population. Not necessarily all the biomarkers will be measured in the entire population. Reference values for time trends will be analysed in at least 200 participants. Specific questions will be answered by targeted biomarker analysis in sub cohorts of adolescents in a case control setting. Adolescents have been involved in the previous campaigns and are well suited to discover time trends. Adolescents carry local exposure fingerprints [14] and evidence is growing that puberty is a vulnerable period for health later in life [15]. Alternatively the research consortium has access to birth cohort and samples that have been recently collected (3xG [16], ENVIRONAGE [17], IPANEMA [18,19]). If needed, time trends of specific biomarkers can be analysed in biobanked samples from birth cohorts that are recruited over the last 3 years in Flanders provided this complies with the policies and ethical and privacy rules from these cohorts, which needs to be formalised.

3. Socio-economic status and chemical exposure and health Recruitment of a study population is easily biased towards participants of higher socio economic class, in particular in a context of environmental studies. Recent efforts showed that it is feasible to include in a birth cohort more participants of the lower income class, of different ethnic origin and of lower education but it requires specific approaches and study material. Moreover we have evidence that SES has a significant influence on chemical exposure and health [13]. Since we expect that the themes mentioned above (eco behavior, use of open space, exposure to emerging chemicals, housing characteristics) are closely intertwined with SES we will develop an approach to include and study social diversity in the adolescent population that will be recruited. Doing so, geographic distribution of the participants will remain as important, given the statistical representativeness of the study that we strive for.

4. Chemical mixtures and their health effects Previous human biomonitoring campaigns have demonstrated frequently consistent associations between chemical exposure and biological effects, despite levels of exposure biomarkers below the current health based guidance values in most of the population. These biological effects, such as reduced birth weight [20], poorer cognitive or motoric capacities [21] and inflammatory changes [22,23] are subclinical and are not considered significant at the individual level. At the population level, however these effects are statistically significant and a considerable impact on population health can be estimated. These statistically significant associations may be partially due to the mixture of chemicals that is present in our bodies and that is not well characterized in Flanders. Current exposure effect studies deal with single pollutants in relation to health outcomes. We will analyse which are the

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predominant mixtures in the population and whether strategies to deal with multiple pollutant exposure and mixtures in relation to health outcomes add to the existing information. Since exposure data and follow up data are available from the cohorts that have been established since 2002, we will (1) take advantage of these datasets to further explore exposure effect associations and (2) pool the data from different cohorts - where appropriate - or validate hypotheses generated in one cohort by data from the other cohorts.

5. Exchange and complementarity to the European human biomonitoring initiative Members of the team have ongoing collaborations with international research groups with experience in human biomonitoring and biomarker research and are involved in the preparation of the European Human Biomonitoring Initiative that aims to expand research related to human exposure to chemicals in Europe. Knowledge and experience from the Flemish program will be put in the European context and it is expected that the European program will give leverage to the Flemish program. As the partners are involved in different international networks and international and national research programs, we will search for win-win situations where knowledge, data and samples can be made of value for the Flemish program of the center, in return this will give visibility of the Flemish program to the scientific community at the international level.

THE CONSORTIUM

This Flemish program can only be realized by an interdisciplinary approach. A consortium of complementary teams will carry out the program. Cooperation in the 3 previous campaigns demonstrated that within well delineated research projects, cross-disciplinarity can be very success- and fruitful. Research teams of the five Flemish universities will participate. This will allow to include aspects related to nutrition and nutritional epidemiology (Ghent University), (molecular) epidemiology (UHasselt) and effect biomarkers (KUL), biostatistics (UHasselt), chemistry and social sciences (University of Antwerp), exposure to organic compounds and effect biomarkers (University of Antwerp), and biomarkers for exposure to metals (Vrije Universiteit Brussel). The association of social scientists and exact scientists will ensure the necessary complementarity for an effective human biomonitoring. The involvement of the research teams from different universities will also allow young PhD students of these groups (team UAntwerpen, UHasselt and KUL) to join the team and get trained in environment and health research themes that are important for environment and health research policies in Flanders. They will develop new capacity for working in interdisciplinary settings. The inclusion of established and experienced research teams from PIH and VITO guarantees continuity and quality assurance of the human biomonitoring program in Flanders which is the core activity of the program. Part 4 of the proposal offers a detailed overview of the capacity and experience of all the hosting research teams. University of Antwerp (promotors Loots, Schoeters and Covaci) is initiator of the center and will be responsible for the administrative and financial management and implements its role in narrow cooperation with the commissioner and the consortium. Prof. Greet Schoeters will be the promoter-coordinator of the consortium. The coordinator will manage the research program, and its milestones and will coordinate the interface with the administrations of the Flemish Government. With respect to the annual planning and technical and financial reporting she will be supported by the initiator. The promotor-coordinator will represent the consortium at the steering group meetings.

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Inside the consortium, the promotor-coordinator will steer and manage the cooperation between the different partners and the follow up of the different work packages. This includes also the evaluation of the progress made, the flexibility towards new opportunities and emerging issues related to EU-initiatives and the input of authorities and stakeholders, distribution of tasks according the work plan, management and the outputs of deliverables. An executive committee of the promotors of the center will be established. This committee will meet at 3 months interval. They function as the management board and will evaluate progress, propose the next annual work plan, prepare reporting to the steering group, publication of the study results and decide on how to accommodate short time assignments on request of the contracting authority. The Executive Committee will keep the overview and has to agree with each order for lab analysis. The executive committee will be co-chaired by the coordinator and initiator. Dr. Vera Nelen (PIH) is the promoter-spokesperson (‘promotor-woordvoerder’) of the Flemish Center of Expertise on Environment and Health. She will act as the interface between the center and the Flemish Government and its administrations as to medical and health-related issues and is also the spokesperson of the center towards the public and the stakeholders. The content of the messages will be discussed and approved beforehand by the executive committee. For external communication the promoter spokesperson will be assisted by specialized research teams. The biomonitoring program will be executed by the field coordinators committee (FCC). This committee will be chaired by Prof. G. Schoeters and Drs. E. Van de Mieroop. Prof. G. Schoeters (chairman) will be responsible for the coordination. The FCC consists of representatives of the different disciplines necessary for the realization of the program. The FCC will at least meet on a monthly basis. Delegations of the Flemish government are invited to attend the meetings as observers. The chairman invites, in name of the management of the FCC, the participants and is responsible for the agenda and reports of the meetings. The FCC works out the details and protocols of the biomonitoring program, described in the long-range plan. The FCC assures optimal integration of all biomonitoring activities of the center including those foreseen in the research projects. It decides on scientific aspects such as the sampling strategy, selection of appropriate biomarkers for the biomonitoring areas and design of the follow-up studies. The choices for biomarkers and target groups will be described in the annual plan and submitted to the executive committee and steering group for final approval. The FCC takes care of the statistical analysis of the data. Decisions in the FCC are based on consensus , if no consensus can be reached, the case will be presented to the executive committee for a final decision. The interpretation of the results will be carried out in an interdisciplinary way, acknowledging the input of the various disciplines. They will be reported to the executive committee. The minority’s point of view will also be reported in case no consensus can be reached. After approval by the executive committee the results will be reported to the steering group and to the stakeholders according to the “Spelregels” document. To facilitate the accessibility of the research results the responsible governmental administrations will be invited to all the meetings of the FCC as observer.

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2. DESCRIPTION OF THE WORK PACKAGES

Figure 1: Network diagram of the FLEHSIV work packages Above the network diagram of all the work packages is depicted. The overlaying Pillar 1 coordinates that the activities from Pillar 2 on the interface between science and policy as well as risk communication are geared to the human biomonitoring in Pillar 3 and vice versa. The output from this 3rd Pillar will contribute to the research in Pillar 4, and again the same holds true in the other direction. The scientific advisory board maintains the overview on all Pillars.

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PILLAR 1

WP1: COORDINATION

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

1 5

P/mnth inkind

7,5 3

The table lists the number of person months contributed by the respective partners throughout the total duration of the project. The dedicated time is either paid by the project budget or offered in kind by the partners.

OBJECTIVES

Coordination: Efficient collaboration among the partners of the consortium Compliance of the program with ethics and privacy aspects

Reporting: Timely delivery of scientific, administrative and financial reports to the contracting authority

Communication and knowledge management: Develop a dissemination strategy for the results and outputs of the program Encourage the use and publication of the results of the program

Management of external relations: Coordinate the interface with the Flemish policy makers Coordinate with the European human biomonitoring initiative and related external initiatives Assure that the program, contributing partners and the program sponsors are well recognised

APPROACH

Task.1: Coordination (M 1-60) Coordination of the work packages will be streamlined through the meetings of the executive committee (EC). The promotor coordinator will organise and chair these meetings, provide the agenda, the invitations and the minutes of the meeting. These meetings coordinate the input for the next annual work plan and track progress of the program. If needed, adaptations of the program will be proposed and submitted for approval to the steering committee. The program leaves some flexibility to accommodate European opportunities and short term tasks (< 5%). Accommodation of these tasks within the work packages will be coordinated through the executive committee . The EC meetings will check compliance of the activities of the program with ethics, privacy, quality criteria and with the guiding rules of the consortium. The EC meetings will agree on dissemination and communication about the program and prepare reporting to the steering committee. The coordination includes the organisation of contacts with the scientific advisory board. The promotor coordinator will act as contact point of the consortium for the contracting authority.

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Task 1.2: Reporting (M 12, 24, 36, 48, 60) Prepare and timely deliver the annual work plans and the annual reports in an error-free format according to the reporting guidelines. Collect financial and administrative information from partners to prepare annual and final reports for approval by the contracting authority. Task 1.3: Communication and knowledge management (M 1-60) Coordinate the establishment of a communication strategy and communication rules in accordance with the consortium agreement. Collect information from the partners on reports, publications and communications related to the programs. Provide access to the reports and publications as agreed in the consortium agreement and guiding rules of the consortium. At the end of the programme, the results will be handed over to the contracting authority. The results will include a database with the biomarker data and metadata obtained during the course of the programme, the study protocol, the questionnaires, the communication forms, the publications in form of reports, peer reviewed manuscripts, abstracts. The use of these results will be subjected to the agreements as specified in the “Beheersovereenkomst” and the “Samenwerkingsovereenkomst”. Task 1.4: Management of external relations (M 1-60) Coordinate the relationship with Flemish policy makers through the steering committee and pillar 2 activities. Report and follow up of activities and knowledge from the European Human Biomonitoring Initiative and propose activities within the Flemish program that synergise with the European program. As several members of the team (Schoeters, Covaci, Nawrot) are involved in various initiatives around European biomonitoring and Exposome, the liaison with international initiatives will be done in first instance by the promotors. If found necessary by the executive committee and if budget permits, a researcher might be appointed in the future to manage the external relations with other EU initiatives. Search for potential collaborations, synergies, external funding and in kind contributions that will capitalise the Flemish program.

DELIVERABLES

- Minutes of the executive committee meetings (4 x per year)

- Annual work plans (M12,24,36,48,60)

- Annual reports with publication lists and lists of the reports that are produced (M 12, 24, 36, 48, 60)

- Signed agreements on exchange with the European Human Biomonitoring Initiative (M12)

- Signed agreements with other projects to exchange data, samples and multiply efforts (M48)

PARTNERS

- The promotor coordinator (G. Schoeters) from VITO is responsible for the scientific coordination of

the work packages.

- The University of Antwerp (Prof. I. Loots) will coordinate the administrative and budgetary

reporting.

- The promotors of the program will participate to the meetings of the EC.

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PILLAR 2: SCIENCE-POLICY INTERFACE AND RISK COMMUNICATION

This pillar groups the initiatives for the 4th cycle of the Flemish Center of Expertise on Environment and health intended to maximise the policy relevance of its research for different policy domains and policy levels, as well as its social robustness and societal relevance. The pillar also includes initiatives to facilitate the transdisciplinary interpretation and policy uptake of the final research results. The experiences and outcomes gained during the three previous cycles of the center, in close cooperation with the policymakers responsible for environment and health in Flanders, will serve as a shared basis for these initiatives. However, in this 4th cycle of the center, special attention will be given to new transversal themes that cross disciplinary and sectoral boundaries, to the multi-level character of environmental health policy (in a European context) and to social inclusion. An evaluation of the research from the previous cyclus of the center by external scientists, commissioned by the department of Economy, Science and Innovation of the Flemish Government (EWI) in 2011, emphasises the inclusion of insights and methods from social scientists as positive. According to the experts, innovative elements in the study design were i.e. the involvement of stakeholders in the interpretation of results, the inclusion of risk perceptions and risk communication, and the study of social inequality and distribution of pollution [24]. This evaluation was considered in the work packages described in this pillar.

BACKGROUND

The relevance of human biomonitoring research for policy and society is diverse. From a scientific point of view the added value of HBM lies in connecting environmental pollution and health outcomes in a general population, by direct and integrated measurement, and taking into account individual characteristics of study participants and influencing factors such as lifestyle patterns and dietary habits. This knowledge allows to inform policymakers about – among others – the actual body burden of environmental pollution, vulnerable subgroups in society, the relative importance of exposure pathways and opportunities to prevent exposures. Secondly, from a political perspective, measuring early health effects, especially among young participants, allows to take corrective actions (long) before actual health damage or disease occurs. And by doing so, protecting citizens from harm, avoiding costs for future health care and providing a base for the evaluation of policy measures. And thirdly, from a more social point of view, by measuring pollution and its health effects directly into the human body, pollution gets personal and citizens get involved in scientific research, which provides opportunities for awareness raising, empowerment and support for policy action. Many illustrations can be found of achievements of human biomonitoring as a basis for policymaking, both internationally [25–27] and in Flanders, as stated e.g. in the call from the Flemish government for this project: “The Flemish Center of Expertise on Environment and Health helped to shape and sustain Flemish environment and health policies in close cooperation with the Flemish administrations, largely by implementing the Flemish human biomonitoring program”. It has, among other things, led to the establishment of specific action plans (e.g. on chlorinated compounds in rural areas in Flanders, on asthma in urban areas and for several hotspots with increased environmental pressure), but also informed the prioritisation of policy goals, answers to parliamentary questions and more recently enabled ex post policy evaluation, since a third cycle of HBM-campaigns in Flanders made it possible to analyse time trends. Human biomonitoring also has a legal basis in Flanders: the 2003 Decree on preventive health care of the Flemish government made it mandatory to perform a HBM program.

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More recently the Flemish minister of Environment highlighted the commitment to “quantify and reduce the impact of environmental pollution on human health”, in a policy outlook for the period 2014-2019. These policy signals underline the importance attached to human biomonitoring as a basis for surveillance, policy development and evaluation. To maximise the policy relevance and uptake of the HBM-research, efforts will be made to open-up the research practice. Not only ex-post, for the interpretation and policy translation of research results (WP2.2). But also ex-ante, to discuss research design and issue framing cooperatively with policymakers and stakeholders (WP2.1). These initiatives are intended to embed HBM in the policy cycle. In addition, transparency and appropriate communication about environmental health risks towards the HBM-participants, professionals, stakeholders and the general public is important to empower citizens, increase support for policy action and improve trust in science and governments responsible for risk management (WP2.3). Three current themes with regard to environmental health research and policy will receive special attention throughout this WP: Focus on transversal (or cross-cutting) policy topics: The policy discussions and initiatives arising from HBM-research in Flanders have always been wide-ranging. Not only limited to rather technical issues such as environmental regulation, but also including topics such as environmental health communication and health promotion, awareness raising, continued (health) monitoring or more detailed research, support for local networking and participation, drafting health advice, etc. Thereby engaging different governments, governmental agencies and other stakeholders active in the field of environment and health. However, the need to broaden the scope to other disciplines and policy domains is increasingly recognised because many topics are cross-cutting and policy integration imposes itself. See e.g. the ‘health in all policies’ (HIAP) approach “to be extended to national, regional and local policies” of the European Commission [28,29]. And the same applies to knowledge production. A review of barriers and facilitators of integration of health aspects in other policy domains by HIA [30] indicated the importance of – among others – development of a shared knowledge base and conceptual understanding, the use of a broad definition of health (e.g. from the WHO) that emphasises physical, social and mental well-being to avoid a focus purely on negative physical environmental impacts, the need for effective partnerships working from an early stage to develop a shared vision, and promoting integration as a non-threatening but constructive process. The center will actively engage itself, in close cooperation with the environmental administrations, to establish contacts and interaction with other domains such as spatial planning, housing, agriculture, youth policy, public health, mobility, product policy, etc. to discuss the cross-cutting issues common to these domains, in first instance the new issues proposed in this project proposal, namely: use of open space and health, eco-behaviour, healthy housing and emerging chemicals. Multi-level character of environmental health policy (and research): Competences and decision-making power for environmental health policy is largely divided over different policy levels. In this field the Flemish government is a major player, but to a considerable degree also dependent on local governments (for the development and implementation of policy), the European Union (due to the frameworks of European regulation), and also the federal government has responsibilities in some subdomains (e.g. product policy). Also with regard to HBM-research, initiatives for European harmonisation are implemented [31].

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This multi-level character of environmental health policy and research will be taken into account in this pillar. On the one hand, Flemish policy accents and research will have to adapt itself and anticipate developments on other levels. But on the other hand, extensive Flemish expertise can inform and help to shape these developments (as has been proven in the past, both locally and supranational). Importance of social inclusion: International research has demonstrated that environmental health risks can contribute or reinforce social exclusion and inequity in society in two interrelated ways: by the unequal or unfair distribution of environmental ‘goods’ and ‘bads’ (like access to green space, housing quality, pollution exposure) and by the unequal opportunities to participate in environmental decision-making and research or access to information. Furthermore, socially disadvantaged groups and ethnic minorities are not only more exposed and more susceptible, but also less resilient, less prepared and less able to recover from environmental health hazards. Experiences in the former cycles of the center identified possible mechanisms of social exclusion also in the Flemish human biomonitoring program, although the interpretation in terms of social inequity was not always consistent [13]. The center will therefore continue efforts for social inclusion as a cross-cutting theme throughout the program, both in the research practice (involving hard-to-reach stakeholders and participants), in the research results (socio-stratifying the biomonitoring results) and in the science-policy discussions.

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WP2.1: CROSS-CUTTING (POLICY) CONSULTATION ON HBM

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

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BACKGROUND

In the first year of the new cycle of the Center of Expertise on Environment and Health an open dialogue will be organized across scientific disciplines, policy domains and stakeholders about human biomonitoring and relevant transversal topics for environmental health research and policy. Many environmental health risks are systemic in nature, embedded in wider environmental, social, economic and political systems [32]. This requires integration of different perspectives and balancing of interests, for both the risk assessment and management. Early involvement of relevant stakeholders and creating openness towards issue framing and research design are important prerequisites to achieve better integrated assessments and understanding [32,33]. We cannot simply assume that consensus exists (or should exist) about the definition and boundaries of the issues under consideration. A well-organized consultation can reveal the (potential) multiple uses and relevance of the HBM-campaigns. Involving stakeholders in an interactive procedure with well delineated discussion topics, avoids that sectoral claims are just aggregated. E.g. discussing which aspects are important or not, to be included in the analysis, or more generally in the policy discussion and communication towards the public. There is another good reason for opening up to the multitude of perspectives. Environmental health risks are often complex risks, both scientifically and socially (see WP2.2 for more detailed background). They are not always unambiguous and thus not easily translated into a surveillance framework. This urges for a rational dialogue with policy makers and stakeholders in order to co-decide on the aspects that need to be taken into account, how to cope with remaining uncertainties, what to accept and what policy to install. Transparency and open dialogue on these aspects is also increasingly demanded by stakeholders that have the knowledge and skills to challenge governments and scientific expertise [34] The call for this project also explicitly emphasises this early and sustained involvement: “It is therefore important that the translation into policy is monitored and assessed from the start of the assignment in cooperation with the government and through consultation/cooperation with relevant policy areas.”

OBJECTIVES

- Discuss the proposed research focus, priorities and frames with relevant scientific disciplines, policy domains and stakeholders, generate input for the research plan and framing of environmental health issues (‘get the questions right’; ‘HBM of value for a broad spectrum of actors);

- Increase awareness about the potential of human biomonitoring in a wider circle so that opportunities for cooperation and integration are more likely to be detected,

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- Stimulate the opportunity for networking among the participating scientists, policy makers and stakeholders to interweave environmental health aspects in other policy domains and vice versa. Specific concerns with regard to environmental health from policy fields as physical planning and infrastructure, health, housing, agriculture and social inclusion, can be taken into account and included in the study.

APPROACH

Relevant scientific disciplines, policy domains and societal stakeholders with regard to the proposed cross-cutting issues in this proposal (use of open space and health, eco-behaviour including agricultural practices such as urban gardening, healthy housing and emerging chemicals) will be invited to discuss the role of environmental health and human biomonitoring within these themes. These discussions will be organised in the starting period of the 4th cycle of the center, to guarantee that results can be integrated in the new HBM-campaign by the end of year 1. 2.1.1. Stakeholder mapping and exploration of sectoral needs: (M1-4) In first instance relevant stakeholders will have to be identified for the different issues, these could include:

- Relevant policy domains and actors, - Scientific disciplines not represented in the center, - Civil society organisations, - Governmental advisory boards, - Representatives of other policy levels.

Every sector has its own concerns and needs. Some of these can be found consolidated in policy strategies, strategic plans or other documents. A basic exploration of these needs, with the help of the Department Leefmilieu – Natuur – Energie (LNE) of the Flemish Government, can be useful in a preparatory phase. Especially the extent to which environmental health is already (or not yet) an important issue, according to different actors in the field, is of particular interest for our discussions (and for opportunities with regard to policy integration in general). For this purpose, a bilateral consultation can be performed (orally or written) to ensure that all individual opinions are captured, before entering the debate. The results of this exploration can also serve as input for the discussions (e.g. underpinning questions for discussion). 2.1.2. Thematic discussions on HBM and framing of environmental health issues: (M5-12) For each cross-cutting issue, a parallel round table will be organised with representatives from policy, science and society. A governmental advisory board can represent a fourth stake, in between policy and society. A mix of perspectives and sectors is preferred, because it allows the participants to react to each other’s opinions and achieve integration of different views. On its turn, interaction will facilitate the development of a common ‘framing’ of the environmental health topics and lead to more applicable knowledge. In addition to actors that have specific interests in the cross-cutting issues under discussion, it is important to include the issues of environmental justice/social inequality and the multi-level character of environmental health policy in each discussion. These more hidden and collective concerns are not easily represented by classical stakeholders in the environmental health domain. That is why for these round tables, the initiator will always invite a key representative for these aspects as well.

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Besides discussion on issue framing, also the research plan will be discussed and openness towards other perspectives will be created. However, the extent to which the research plan can be adjusted has some limitations. The Center of Expertise on Environment and Health performs HBM-research in Flanders since 2001. This means that a lot of data and expertise is generated, but also that adjustments to the research plan are to a certain extent bound to past decisions. E.g. the choice of age groups, prioritization of biomarkers and research topics, used methods etc. These aspects need to remain stable for a large part to allow the analysis of time trends. In addition, also the policy priorities of the contracting government (the department of Environment) must be covered sufficiently. In the past, some of these aspects have already been subject of deliberation with stakeholders. For instance, in 2012, the center organised an extensive multi-criteria analysis with scientific and Flemish policy experts to prioritize the biomarker to be measured in FLESHIII. The outcome of this ranking was discussed in a joint hearing of the governmental advisory boards on environment and health [35]. These round tables can be repeated during the HBM-research period (in year 2, 3 or 4), to continue interaction, mutual learning and networking. E.g. scheduled after a meeting of the Steering Committee, centered around one topic at a time, once for each topic (see WP2.2). Anticipating scientific valorisation, relevant questions are: (1) How convergent-divergent are environmental health framings of different policy sectors; are these frames rooted in the domains of public health, environmental policy and/or sustainable development; in place-based or people-based policy traditions? (2) Do needs and concerns of societal actors reflect these framings? (3) Do key issues (the new themes) facilitate the expression and sharing of frames? And policy integration? (4) Can round table initiatives facilitate common framings and understanding? (5) Do stakeholders embrace a broad or strict range of policy measures?

DELIVERABLES: (M12)

The reports of parallel thematic round tables, with a focus on the cross-cutting themes proposed in this research proposal: (incl. identification of opportunities for the upcoming HBM-campaigns and policy integration in general)

- Use of open space and health; - Eco-behaviour and healthy housing; - Emerging chemicals.

PARTNERS

Lead: UAntwerpen (Loots): concept, process architecture and reporting of the round tables. With contributions of other partners of the consortium, for participation in the debate and scientific support. For the process guidance, cooperation with the department of LNE is expected. For reasons of proximity and presence in the administrative heart of policy making, in Brussels, also the practical organisation and hosting might be taken up by the commissioner. A cooperation, similar to the implementation of the phased Action plan will be set up.

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WP 2.2: SCIENCE – POLICY TRANSLATION (‘PHASED ACTION PLAN’)

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

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BACKGROUND

Although HBM-research yields a lot of relevant data on environmental health (body burden of environmental pollution, determinants of exposure, vulnerable subgroups, time trends etc.), the evaluation of the scientific results and it’s translation into policy action is often complicated by both scientific and social complexity. From the scientific point of view, environmental health risks are often faced with large (partly irreducible) uncertainties, limited information and scientific debate [36–38]. E.g. the absence of guidelines for health interpretation (for many chemical substances and early health effects), confounding variables, the fact that measurable exposures and (early) effects do not automatically lead to disease, uncertainty about the impact of multiple exposures and effects, etc. complicate the interpretation of the actual health impact of environmental pollution and nurtures scientific debate. From a societal point of view, environmental health risks are interwoven with our way of life, our perceptions, norms and values, and may have unequal social impacts [39–41], giving rise to social and ethical debate, the need to reconcile (contrasting) interest or lack of support for policy measures. New approaches have been proposed to deal with these complex, unstructured problems in a more effective way, such as the extended peer community [36], Mode II knowledge production and transdisciplinarity [42,43] and more recently pragmatic approaches to expand the scope of impact assessments and risk governance [32,44]. Hage et al. (2010) defined some main issues that are at stake within these new approaches [45]: the quest for the production of knowledge that explicitly acknowledges its own frontiers and uncertainties, the quest for more legitimate knowledge, the quality control of this new type of knowledge, the organization of more applicable knowledge and the inclusion of non-scientific expertise. Inspired by these approaches, a structured and participatory procedure (‘phased action plan’) was developed and implemented during the first cycle of the center to facilitate the evaluation and policy uptake of HBM-research results [46]. We could label this as experimenting with a novel knowledge-policy arrangement. The successful application of this procedure made this approach a guiding example for the successive cycles of HBM-research of the center, leading to different action plans [47]. The phased action plan procedure intertwines the knowledge with the policy cycle by combining scientific analysis and deliberation on policy options, based on the analytic-deliberative approach [48]. The phased action plan mobilises knowledge and expertise from different sources (scientific and non-scientific) and evidence-based criteria are complemented by policy- and social considerations to underpin decisions, with the final aim to arrive at policy options that are both scientifically and socially robust.

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General principles of the phased action plan: - Structured and iterative process: The phased action plan is structured around several phases,

each with its own objective. The conclusions of each phase are used as a starting point for the next phase. Subdividing the decision making process in more manageable, iterative sub-questions leads to better understanding and transparency on final policy decisions and fosters a mutual learning process among the participating actors.

o Pre-phase: pre-selection of relevant research results within a science-policy setting. o Phase I: prioritization of HBM-results based on scientific, policy and social criteria. o Phase II: more detailed analysis of the issues with the highest priority and co-production

of appropriate policy options. o Phase III: elaboration and implementation of policy actions. o Phase IV: evaluation of policy actions.

The pre-phase and phase I and II are organized collaboratively by the center and the contracting government. Elaboration, implementation and evaluation of policy (phase III and IV) remains the responsibility of respective governments (potentially in collaboration with other stakeholders).

- Pragmatism: Absence of full scientific certainty cannot be used as an argument to postpone policy decisions, in some cases in line with the precautionary principle. The phased action plan facilitates decision making in a context of complexity, on the basis of the (appraisal of) best available knowledge and by deliberating on uncertainties, stakes, norms and values.

- Transparency and participation: Involving relevant experts, policymakers and societal stakeholders in the decision making process leads to mutual learning and guarantees that all relevant perspectives are taken into account. Transparency on all aspects of the process is essential to gain trust and cooperation off all parties involved. This approach has been implemented successfully in the past, in different policy contexts (on local and regional level), and will be the basis for future HBM-campaigns. Advantages of this approach include: broadening the knowledge base, increase trust among actors involved, mutual learning, increase support and effectiveness of policy action.

OBJECTIVES

- Transdisciplinary interpretation and prioritisation of HBM-research results, based on three general criteria: scientific evaluation, policy relevance and public concern.

- Translation of research findings (and related public concerns) in a problem solving strategy. - Co-production of recommendations for integrated solutions, eventually leading to action plan(s)

by policymakers and societal stakeholders and to policy integration: interweaving environmental health and other policy goals.

APPROACH

As soon as new HBM-research results become publically available (expected by the end of 2019) a phased action plan will be implemented by the center in cooperation with the contracting government. In the preceding period (at the latest, in the course of 2019) an updated concept for this phased action plan will be developed, adapted to the new context of the center’s 4th cycle of HBM-research, and taking into account the developments of the cross-cutting (policy) discussions up to then (see WP2.1). As far as this can already be anticipated, it will likely be beneficial to continue the cross-cutting dialogues and build on growing awareness. It can be expected that emerging policy accents and adjacent research projects are established with which exchange might be of value.

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Alternatively, it might be useful to involve specific target group(s) as soon as HBM-results are available and discussions shift to policy action (e.g. in focus groups). One initiative in this respect has already been prepared as an ‘in kind’ contribution of the University of Antwerp. The HBM-results of the former cycle are expected in 2015 and will become available for interpretation in 2016. In cooperation with the province of Antwerp, a regional interpretation for local policy needs might be started up by the end of 2016. A community of practice, guided by a cross-disciplinary UAntwerp-team (Loots, Schoeters and Weyler) will discuss the study results in line with the principles of a phased action plan. Two researchers, one with a biomedical and one with a social scientific background will support the exercise. However, the proposal firstly has to be accepted (in competition with other proposals); the selection is expected in December 2015. 2.2.1. Updated concept for the phased action plan following the communication of a new cycle of HBM-results (2019-2020): (M42-44) The procedure of the phased action plan (previously developed by the center) should be understood as a coherent set of guiding principles, rather than a script. Mainly because the social and policy contexts are important factors determining the suitability and feasibility of this kind of processes. However, several context-variables are currently difficult to predict: e.g. the nature and severity of the research results and (expected) societal resonance, the success (or lack of success) of the cross-cutting discussions (in WP2.1) and the demand for continuation of these initiated interaction processes. Additionally, the concept also needs to be adapted to the new themes in this project proposal, namely the focus on cross-cutting themes, social inclusion and multi-level character. 2.2.2. Implementation of phased action plan (phase I en II): (M48-60) The pre-phase and phase I and II of the phased action plan will be organized collaboratively by the Center and the contracting government in year 5. Although the final concept for the phased action plan still has to be operationalised (see 2.2.1.), two alternative options for consultation of stakeholders can already be considered:

- Continuation of cross-cutting (policy) dialogues: In the assumption that the cross-cutting dialogues initiated in year 1 (see WP2.1) are successful, continuation of these interaction processes is premised. During the HBM-research period itself and included in the updated concept for the phased action plan. Success can be evaluated by, among others, engagement of key stakeholders, productive interactions during previous meetings and/or demand for continuation by participants. This will be evaluated cooperatively with the contracting government. Advantages of continuation include: growing awareness, mutual learning, trust between participants and, because of these prior advantages, higher chances for integration and cooperation. Potentially not all initiated interaction processes will be equally successful, and thus a decision will be made for each topic separately. In case that previous interactions where not successful, an alternative will be proposed.

- Focus groups with target groups: An additional perspective that is of particular relevance is the citizens’ perspective, and more specifically the target groups that are subject to the HBM-campaigns and considered policy. This perspective is already basically taken into account by the perception questionnaire (see WP2.3), although focus groups would be useful to complement these insights. This method is better able to figure out the dynamic nature and triggers behind perceptions. And additionally the support for certain policy actions can be discussed and focus groups can be differentiated according to different target groups. However, because of limited resources, these focus groups can only be organised as an alternative for the continuation of the cross-cutting dialogues.

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Anticipating scientific valorisation, relevant questions are: (1) Which perspectives on the science-policy nexus inspire the phased action plan? (2) Which criteria for evaluation of the phased action plan can be defined? (3) Which criteria for assessing the outcome of phased action plans are welcomed by policy makers?

DELIVERABLES

- Development of process architecture for the implementation of the phased action plan, following the communication of a new cycle of HBM-results (2019-2020), including relevant evaluation criteria, based on the evaluation framework developed during the previous cycle of the Center (M44).

- Implementation and intermediary reporting of phase I and II (in cooperation between the research team and the contracting government) (M60).

- Paper on perspectives for evaluation of the phased action plan (M48).

PARTNERS

Lead: UAntwerpen (Loots) and VITO: concept development, desk research and process guidance. Input from the other partners for the input on and presentation of specific technical aspects. [In close cooperation with LNE]

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WP 2.3: RISK COMMUNICATION AND SOCIAL INCLUSION

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

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20 1

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0,5 2

BACKGROUND

Communication about environmental health risks and human biomonitoring is challenging and requires careful consideration. The ambitions are to raise awareness, trigger behavioural change (to prevent both pollution and exposures), strengthen trust in science and authorities responsible for environmental health protection, empower disadvantaged groups and create support for policy measures. But on the other hand unnecessary anxiety needs to be avoided and scientific uncertainty and knowledge gaps need to be addressed. One of the main problems in risk communication is negligence of the social context [49]. There is growing recognition that technical approaches with a one-sided transfer of risk information from experts to the lay public should be replaced by a more dialogical approach, with focus on participation and cooperation between scientists, policy-makers and the public [50]. Important in this approach is the fact that different perceptions and knowledge production modes are relevant and should be respected. Overcoming the gap between science and the public is still one of the biggest challenges of risk communication. Mutual understanding is necessary to create trust in order to solve problems that are both scientifically and socially complex. Risk communication is no panacea though, but will result in fewer misunderstandings and ‘better’ (informed) conflicts [51]. From the social scientific perspective moreover, in order to achieve social change, taking perceptions seriously is a prerequisite [41]. Finally an important reason for taking into account perceptions of the affected groups and lay knowledge is simply the fact that science itself suffers from many uncertainties and unknowns. Lay knowledge may contribute to the better understanding of problems. A social scientific perspective on risks thus broadens the horizon and offers other ways of understanding and describing reality and the way people socially construct their own realities [41]. With regard to communication of human biomonitoring results to study participants, scientists must weigh participants' right-to-know and the potential benefits of receiving individual information against the possible psychological or financial harm of trying to make sense of data that may not provide a clear picture of potential health implications [52]. Although most human biomonitoring studies follow an approach driven by clinical ethics, and do not disclose individual results [53], some recent empirical studies from a more participatory approach show that reporting-back individual results has important benefits like increasing trust in science, retention in cohort studies, environmental health literacy, individual and community empowerment and motivation to reduce exposures [54,55]. Studies conducting participants’ evaluation observed on the other hand no excessive fear or anxiety after receiving personal biomonitoring results [56,57].

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Important elements in the practices of effective reporting-back are designing protocols and communication plans in partnership with study communities [52,55], understanding the disclosure preferences of the study population and tailoring the mode of reporting-back [58], and including contextual information about health implications and exposure reduction strategies to help individuals understand the meaning of their results [54,59]. Another point of attention in the participatory approach on risk communication and management is the inclusion of all relevant perspectives and stakeholders, especially those with fewer capacities or agenda-setting power. This implies looking at environmental health risks through a ‘justice’ lens. Literature on environmental health inequalities demonstrate that socially disadvantaged populations are in ‘double jeopardy’ of environmental health risks, since they can be more exposed to environmental pollution and more susceptible to its damaging health effects, while having a smaller contribution to environmental pollution [60,61]. This research is rooted in the environmental justice movement in the US, which showed that hazards in the physical and chemical environment disproportionately affect those individuals, households and neighbourhoods that also face hazards in their social environment [62]. Research and politics outside the US is rather scarce, but in Europe there is a growing interest in environmental health disparities. For instance, the fourth and fifth Ministerial Conferences on Environment and Health organised by the WHO clearly stated that the unequal distribution of environmental health conditions and risks by a range of socio-demographic determinants is a major challenge for public health governance [63,64]. Also the European Environmental Agency stated in a report on environmental health that “the environment-related share of the burden of disease depends strongly on socioeconomic aspects such as income” (2005) [65]. Paradoxically, while there is consensus on the existence of a close relationship between social inequality and environmental health, exploration of this link is still underdeveloped. One of the main identified knowledge gaps in the empiric evidence for Europe, is the fact that most studies use aggregated data to correlate the distribution of external exposure (emissions, pollution proximity) and indicators of social deprivation. This gives only a partial view of the processes involved in environmental inequalities because it may not reflect the individual experience [66]. There is a lack of individual data on the internal exposure to (a mixture of) chemicals, e.g. from human biomonitoring research, and available evidence shows more nuanced results which do not always support the environmental justice hypothesis [67,68]. For instance, concerning the internal dose of environmental exposure, research reveals that the lowest social classes are not always exposed to higher concentrations. This was also found in the data of the first and the second Flemish Human Biomonitoring program, and was most pronounced within adolescents [13,69]. Unfortunately, most human biomonitoring studies are not designed to detect social gradients. At least three important shortcomings can be distinguished:

- Firstly, HBM-studies are easily biased towards higher social classes. Ethnic minorities and socially disadvantaged groups are less represented, and thus less visible in most biomedical studies and preventive monitoring surveys because they experience more participation barriers. This social bias not only undermines the validity of scientific data, it also complicates policy actions to identify and tackle environmental health inequalities.

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- Secondly, most human biomonitoring studies either do not include social indicators in their questionnaires and analysis or tend to consider SES data only to control for potential confounding. But rather than claiming to have ‘controlled for SES’, researchers should acknowledge the potentially relevant aspects of SES when interpreting findings of environment and health studies [70,71].

- Thirdly, the communication vocabulary and reporting back of individual biomarker results is often matched to the preferences of middle and higher social classes. However, to ensure effective communication, there is more need for a flexible system of disseminating results (for instance written versus oral format), tailored to the education level and ethnic background of study participants [58].

OBJECTIVES

- To foster transparency on research design, results and research practice. - Strategy to report-back individual and group results to study participants (for practical

implementation see WP3.7) - Taking into account risk perceptions and investing in trust. - Taking into account mechanisms of social exclusion and inequality as a cross-cutting theme,

both in the research practice (involving hard-to-reach stakeholders and participants), in the research results (socio-stratifying the biomonitoring results) and in the science-policy discussions.

APPROACH

The external communication of the center’s results will be elaborated on the basis of social scientific insights presented in risk communication literature and the insights acquired during experiences with external communication in former biomonitoring campaigns (2002-2006, 2007-2011 and 2012-2015). Content-related, procedural and institutional requirements will be used as prerequisites for adequate communication. Initiatives for facilitating participation are a logical consequence of these contemporary scientific insights in risk communication literature and practical guidelines. In other parts of this application, specific initiatives are already announced and described in detail (WP2.1 Cross-cutting dialogue on HBM and WP2.2 Phased action plan) and will not be repeated here although they can be categorized as risk communication activities. Initiatives for social inclusion will be integrated in the research practice (WP 2.1, 2.2, WP 3.3, 3.5, 3.7 and WP 4) but will be framed in their social scientific context and described under 2.3.3. 2.3.1. Golden rules for external communication in a context of risk: (M13) Starting points: The external communication is linked up to the following starting points: - Researchers and government should provide transparency on the research design and

methodological background to individual participants and to intermediaries and not only on the research results;

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- Scientific controversies and uncertainties are normal, both as a consequence of the complex character of environmental- and health research and as a consequence of the social construction of knowledge. Lack of unambiguous conclusions about environmental factors and health effects and scientific uncertainties will, to a large extent, continue to dominate the debate on environment and health, so application of adequate communication procedures will be necessary;

- Experts, citizens, authorities and polluters perceive risks in different ways; every perspective is valuable (different problem definitions, different solutions to be taken into account). The strategy to fill the gap between objective and perceived risks by merely trying to convince the public of the expert view (the traditional one way-risk communication by means of merely informing the public) is not adequate. Persistent controversies about the environment and health are energy-consuming for all actors involved. Moreover, these definitions and risk perceptions are dynamic: they evolve.

These rules reflect an open perspective: they will support interaction with the public and societal actors, and between the scientists of the center and the contracting government. Participation is considered fruitful for the development of knowledge in complex issues, fruitful for the support to define problems and solutions of environmental health-issues and fruitful for gaining trust between the parties. These starting points will be operationalised in quality standards and practical rules guiding the communication of the Center (e.g. on timing and division of tasks). An important example of such practical rule is that participants in the research shall always be the first external actors to be informed about the research results, i.e. they should never be informed later than the general public. Organisation of communication: The organisational conditions for external communication are: - In line with the general principle of integrated social scientific research (instead of end-of-the-line

communication); only integrated communication initiatives will be organised. This means that in principle, external communication activities will be prepared within the FCC and with the Co-ordinator and approved by the steering group. Interdisciplinary cooperation (involvement of different scientific disciplines) is essential.

- Shared external communication means that the responsibility and the work load for the external communication are discussed and agreed within the FCC, with the Spokeswoman and the Co-ordinator of the center and with the steering group. Thanks to the previous HBM-cycles, there is has ample experience with an always challenging, but workable task division.

The following tasks and initiatives will be implemented in order to support the goals and conditions mentioned, with transparency as a key condition. The guiding rules and communication strategy from the previous generations of the center will be used as a basis, but will be adapted to the context of the 4th generation of the center: - Upgrade and consolidation of the ‘Spelregels’ (guiding rules) for external communication of the

Center of Expertise on Environment and Health and aligned with the Steering Committee of the Flemish government. The basic principles, quality standards and rules in these guiding rules should guarantee a transparent and open external communication of the results of the consortium, focused on trust of all parties. After consolidation the rules are published on the center’s website (http://www.milieu-en-gezondheid.be/).

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- Discussion on the common communication strategy of human biomonitoring results, to be agreed in the FCC, the Consortium Management Team and with the Steering Committee. Also the Flemish environmental health network will be invited to comment the strategy. The communication strategy is based on the starting points of the agreed guiding rules. A communication plan will provide more detailed information on the implementation:

o The goals or functionalities of the external communication (in order to start from a common perspective and common expectations);

o Individual steps or initiatives, detailing ‘what/how, why, who and when’. The who-question will include attention to the different roles in risk communication, participants in the study, policymakers, experts and medical and environmental professionals as practitioners and local health professionals (e.g. Medisch MilieuKundigen), stakeholders and the public in general;

o The internal operational aspects, responsibilities and task division; o Mode of ex-post evaluation.

- Evaluation of each (external) communication in collaboration with the Spokeswoman; - Input for updating of the center’s website; - Input for ‘Gezond Milieu’, an electronic newsletter of the Flemish environmental health network. - Where feasible, the communication format of HBM-results to participants will be tailored to better

meet the needs and barriers of socially vulnerable subgroups. Anticipating scientific valorisation, relevant questions are: (1) Which guidelines do primers on risk communication recommend? (2) What are best practices for reporting back study results; does the scientific literature report an evolution? (3) How can an interdisciplinary consortium manage to open up the research setting for (relevant) outsiders? 2.3.2. Investigating risk perception: (M18, M44-47) Aim and relevance of risk perception questionnaires: The general questionnaire of the HBM-campaign will include a questionnaire on the perception of environment and health risks and trust of participants in different sources of information. Complementary questions on socio-demographic and socio-economic characteristics of the participants will allow to assess awareness, opinions and attitudes on environmental health risks of specific subgroups in the Flemish population. Some questions will be adopted from the annual survey on sociocultural shifts in values, attitudes and behaviors, organized by the Research department of the Flemish Government (SCV-survey van de Studiedienst van de Vlaamse Regering). Perception research by way of questionnaires has some disadvantages. These disadvantages refer to the static character of surveys while perceptions are dynamic as they are social constructs, the possible bias due to closed questions, and the lack of information for further interpretation of the individual and group results. But the fact that the biomonitoring is being repeated (and even sometimes longitudinal), offers the possibility of monitoring perceptions over time. And last but not least, data on the perceptions of participants is of extra value for providing tailored communication plans and within the phased action plan. Research questions: - Which trends can be identified in subsequent risk perception survey parts? - Which perception results are of importance for the phased action plan?

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Tasks and initiatives: - Update of the perception questionnaire. - Data analysis and reporting, in line with the time schedule of the biomonitoring campaigns and the

internal and external communication of the results; - Support for including results in the phased action plan (see WP2.2) 2.3.3. Social inclusion aspects Aspects of social inclusion will be elaborated along four tracks during the study period: in the cross-cutting consultation initiatives (see WP 2.1) in the recruitment fase (see WP 3.3), in the post-hoc analyses on socio-stratification of HBM results (see WP 3.5) and in the tailoring of communication formats for more social vulnerable groups (see WP 2.3 and WP 3.7). Social inclusion in recruitment phase (M18) Although research showed that socially disadvantaged groups and ethnic minorities are more exposed to environmental pollution and more susceptible to its health impact, these groups are systematically underrepresented in biomedical studies [72]. This paradox not only undermines the validity of scientific data (selection bias), it also impede targeted policy actions and reinforce existing patterns of social exclusion. Within the latest human biomonitoring of newborns in 2014, we therefore designed and implemented a parallel recruitment strategy to enhance the participation of socially disadvantaged pregnant women. Our strategy was based on three pillars: (i) modify study procedure (professional advice on the ethnic matching and vocabulary of communication materials and study design), (ii) networking with community organisations, intermediates and gatekeepers, and (iii) implement personal buddy system for participants (recruitment of and support for participants by trusted third-party women with same ethnic background as target group). Our adapted strategy showed that, by investing in direct, person-to-person contact by trusted buddies and supported by practical advice on cultural and linguistic sensitivity, it is possible to increase the participation rate of socially disadvantaged subpopulations in biomedical research. The planned recruitment of adolescents in the fourth generation of the center offers good opportunities to use the school as an entry point for social inclusion. Human biomonitoring campaigns with adolescents in the past have shown a strong correlation between the school type and educational attainment of the parents. Within the study sample of our latest adolescent campaigns (2013-2014), 90% of the adolescents with vocational schooling had parents without higher education, and 33% lived in a household with an income below the poverty line. After some targeted consultations with field organisations and experts, and in close collaboration with the center, we will design and implement additional initiatives within the global recruitment strategy to better capture social and ethnic diversity in the study sample. Possible actions could include: tailored info sessions in classes (to stimulate supportive group participation) and the design of an appealing and translated info brochure for parents and adolescents. Socio-stratifying HBM results (M44-47) According to the WHO, one of the greatest weaknesses in work on environmental health inequalities in the European region is the lack of data and evidence. Especially, the “limited stratification of environmental risk exposures by factors such as age, gender, income, ethnicity, employment and education – makes it difficult to identify vulnerable groups and the magnitude of inequality” (WHO 2012, p.136).

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Since 2009, the center performs post-hoc analyses on the socio-stratification of the HBM results. Four conclusions can be formulated from previous analyses (Morrens et al. 20012; 2014):

1. Depending on the (type of) pollutant, adolescents with a lower SES have higher or lower internal

concentrations. Exposure to some heavy metals (lead, cadmium and copper) is negatively

associated with SES, while exposure to POPs (PCBs, pesticide DDE and flame retardants) is

positively associated with SES.

2. Distance to (suspected) pollution sources is not a principal factor in this observed social

differences in exposure. Lifestyle factors and dietary behaviors appear to be more important

determinants of social gradients in internal exposure. Although for some biomarkers, social

gradients could also be explained by demographic (sex, age) or biometric factors (BMI).

3. The ethnic background of adolescents seems to be an associated underlying characteristic of the

observed social gradients.

4. The use of different SES indicators (education, income) show different results.

To further elaborate on the above conclusions, we will again stratify the results of the fourth FLEHS study according to educational attainment, income of the parents (as indicators of socio-economic status) and ethnic background of the adolescent, and use multiple regression analysis and structural equation models to determine intermediary factors and pathways. Research questions:

- Is there an association between indicators of SES/ethnic background and biomarker concentrations?

- How can we explain these associations? Is SES a proxy for personal factors (age, BMI, …), lifestyle factors (smoking, dietary patterns) or geographical factors (distance to busy roads)?

- Are there time trends in the observed social gradients in biomarker concentrations? Do the social gradients for heavy metals and POPs become steeper when we compare the data from consecutive HBM-campaigns on adolescents?

DELIVERABLES

- ‘Spelregels’ (Guiding rules) (M12) - Communication plan(s) (M48) - Peer-reviewed paper on risk communication strategy (M48) - Adapted recruitment strategy and actions for social and ethnic diversity (M18) - Peer-reviewed paper on socio-stratified HBM results (M60)

PARTNERS

Lead: UAntwerpen (Loots), in cooperation with the coordinator (VITO) and spokeswoman (PIH).

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PILLAR 3: HUMAN BIOMONITORING PLATFORM

BACKGROUND

This pillar establishes the human biomonitoring platform and is central to the program as it connects to

the science-policy pillar to get input for problem framing and prioritisation of the chemicals to be analysed;

the research pillar which will make use of the biomarker data and meta data to address specific research questions and relate the biomarker data to environmental and health data.

This central position will be effectuated in the field coordinators committee (FCC) that convenes on a monthly basis to develop the different tasks of this platform. Each research team will be represented in the FCC and will contribute. Responsibilities for the tasks are distributed among the partners (see Table 1). The consortium has worked efficiently and successfully together in the past and has developed a workflow that will be also kept in the present cycle to guarantee continuity and quality of the output. However we will also learn from the past and will adapt some approaches to increase efficiency and to be in line with the reduced budget compared to previous campaigns. General Objectives of the HBM platform

To generate in a cost-effective way information on distribution of internal human internal chemical exposure in a sample of the Flemish population that is representative to Flanders in relation to geographic distribution and social economic status.

To compare the levels of internal pollutants with health based guidance values and reference levels from other international studies;

To measure and report levels of internal exposures to emerging pollutants that relate to where and how people live (eg. indoor and outdoor pollution) and to new upcoming life styles (eg. eco-behaviour). This will be achieved by a nested case control design.

To gain more detailed knowledge on potential sources of these emerging pollutants

To evaluate time trends in human internal chemical exposure in a sample of the Flemish population that is representative in relation to geographic distribution.

To construct a database and make the data available to the other work packages

To continue building up a biobank of specimens representing the Flemish environmental exposure burden

To disseminate the results of the human biomonitoring to stakeholders, participants, and the scientific community

To ensure adequate communication to study participants in line with ethics, privacy aspects and internal rules of the center

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Table 1: Overview of work description of pillar 3

WP title Main deliverables Partners (lead)

WP3.1: Study design Selection of

Exposure biomarkers

Sampling matrix

Target population

Study protocol approved by ethics board, privacy commission, and by steering group

VITO UGent PIH UA UH KUL

WP3.2 Questionnaires Database with questionnaires (including perception questionnaire)

PIH VITO UA UGent

WP3.3 Recruitment and sampling

Signed informed consents Communication material to participants to report back Distribution of results to participants

PIH VITO UA

WP3.4 Toxicological analysis Levels of biomarkers QA reports of measured biomarkers

VITO VUB UA UH

WP3.5 Construction of database and data analysis

Database with biomarkers and metadata

VITO PIH UA UH VUB UGent

WP3.6 Biobanking Aliquoted and stored samples ( blood, plasma, DNA, RNA, urine, hair)

VITO

WP3.7 Reporting Report with reference values Summary report and manuscript on time trends

VITO PIH UA UH UGent VUB KUL

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WP 3.1 : STUDY DESIGN

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

4 6 3 5 2

P/mnth inkind

5 2

BACKGROUND

Until now the FLEHS studies have measured levels of pollutants in three age groups (pregnant mothers that were recruited in the maternities, adolescents of 14-15 yrs old, adults (20-40 yrs–FLEHSII; 50-65 yrs – FLEHSI & III) that have been recruited in 8 different parts of the region (FLEHSI), that were representative in relation to population density per province (FLEHSII and FLEHSIII) or were sampled in hot spot areas (FLEHSII and FLEHSIII). In FLEHSIII there were specific efforts for recruitment of participants from different ethnic origin, low income, low education level. This multi-stage sampling study design allowed to generate reference values of exposure markers from 50 pollutants in the different age groups. These levels could be compared with health based guidance values and with biomarker levels from other studies (mostly international) [6].

OBJECTIVE

To design a protocol for cost efficient generation of biomonitoring data that 1) allows to generate reference biomarker levels for new emerging chemicals, 2) allows to analyse human exposure trends and 3) will address the different research questions that are raised in the program: environmental Exposure and health in Flanders in relation with green/grey/blue/agricultural spaces and eco-behaviour. New and emerging chemicals will be prioritized based on their relevance for assessing exposures from green/grey/blue/agricultural spaces, eco-behaviour.

APPROACH

Based on the input from the cross-sectoral consultations (Science-policy pillar 2) of policy makers and stakeholders, combined with scientific input from members of the consortium and taking into account the priorities listed in the call (see Research pillar 4) a dedicated study design will be developed. We will not continue recruitment in all three age groups. If appropriate for the selected chemicals we will recruit adolescents. Adolescents represent well the impact of their local environment where they lived often from their birth on. They have no professional occupation as many adults have and they commute less compared to the adult population. The age group of adolescents can be recruited in an efficient way through schools. We have optimized our recruitment procedure for this age group during the last decade. The biomonitoring raises awareness and early warning signals for later health risk are important in this age group. Hence, there is growing evidence that puberty is a vulnerable life stage and may benefit from environmental health protection. Toxico-kinetic and toxicological information of the specific chemicals will be used to select the most appropriate biological sample for analysis of the selected biomarkers (eg. urine or blood).

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We aim to select a population of 600 adolescents. They will be selected by a two-stage sampling design with representative distribution over the provinces of Flanders. They will be sampled for urine, blood, and hair and the samples will be stored in a biobank (see WP3.6). From each of the adolescents we will have questionnaire data (see WP3.2). 1) Reference biomarker levels To obtain new reference values for new chemicals: we will first calculate statistical power based on available data in the literature in order to define the sample size of the cohort. The subcohort will be selected with representative distribution over the provinces of Flanders from the sample of 600 adolescents. 2) Analyse human exposure trends To follow time trends: we will use the study design of FLEHS II and FLEHS III for adolescents and select a subcohort of 200 adolescents by a two-stage sampling design with representative distribution over the provinces of Flanders. 3) To address research questions related to exposures and health from green/grey/blue/agricultural environment, eco-behaviour (homegrown food, indoor environment) and energy-efficient housing, we will use a nested case-control setting. Selection of the study participants will be based on power calculations and on information from the questionnaires to identify cases. If the adolescent population is not relevant for the chemicals under study, we will explore the possibility to analyse the exposure biomarker in biological samples from birth cohorts (mothers, newborns) that are recruited in other projects in Flanders. These other cohorts are listed up with the in kind suggestions of the participating research groups (see WP4.3). The study design will be elaborated through a collaboration of different disciplines present in the FCC (biostatistician, epidemiologist, toxicologist, chemist, social scientist, fieldwork responsible) The study design will be translated in a study protocol that will be submitted for approval to the ethics committee of the University hospital of Antwerp (UZA) and for authorisation to the 'Vlaamse Toezichtscommissie voor het elektronische bestuurlijke gegevensverkeer' (Flemish Supervisory Committee for Electronic Administrative Data Flows) and the 'Sectoraal Comité van de sociale zekerheid en van de gezondheid' (Social Security and Health Sectoral Committee).

DELIVERABLES

- Selection of biomarkers, sampling matrix for analysis (M 6, M 18) - Study protocol for time trends (M 12) - Study protocol for emerging chemicals reference values (M 18) - Study protocol for study on exposure to eco-behaviour related life style factors (M18) - Study protocol for study of exposure and health in relation to proximity and accessibility to

blue/grey/green/agricultural spaces (M 18) - Approval from ethical committees (M 18) - Authorisation from the Flemish Supervisory Committee for Electronic Administrative Data Flows

(M18)

PARTNERS

All partners of the consortium Lead: VITO

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WP3.2 QUESTIONNAIRES

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

1 1 5 2 7

P/mnth inkind

2 2

BACKGROUND AND OBJECTIVES

Questionnaires are meant to obtain information on possible exposure routes, influential factors and on specific health aspects.

APPROACH

In the new FLEHS cycle, detailed questionnaires will be developed and recycled as much as possible from the previous FLEHS cycles in order to allow comparison. However, they will also be updated on exposure routes of emerging chemicals and possible influential factors as identified in literature and questionnaires used in other population studies. Concerning specific health endpoints validated questionnaires will be used (e.g. ISAAC questionnaire on asthma and allergy [73], Strength and Difficulties questionnaire [74]). We will also look into the questionnaires available in the database of the Research department of the Flemish government (Studiedienst van de Vlaamse Regering (SVR)), since they have a large set of questionnaires they also use in surveys. Using their or similar questionnaires will allow to compare the responses obtained earlier or in another population group. We will benefit from the lessons learned with the Addendum of the previous cycle of the human biomonitoring program. The communication material will be adapted to make the program better understandable for participants from different socio-economic environments. In the past, paper questionnaires were sent to the participants for self-administration, whereas now, an effort will be made to invest in software allowing digital responses. This will benefit not only the work load of the response registration but also the quality controls and completeness of the data. A digital platform for asking questions to the participants would allow to present shorter questionnaires on a more frequent basis, thereby reducing the burden of completing it for the participant. We will investigate the possibility to get access to computers at school for the study participants but nevertheless anticipate and respect socio-economic user differences. Besides electronic questionnaires, participants will still have the choice to answer the questions on paper. The anonymous responses on the questionnaires will be archived in a database linked to a codebook allowing to link the answers to the original questionnaires (see WP3.5).

DELIVERABLES

- Digital platform to interview the participants (M18). - Paper questionnaires (M18). - Database with archived questions (M36) - Database containing information on exposure routes, influential factors and specific health

effects of each participant (M48).

PARTNERS

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UGent, VITO, PIH, UAntwerpen Lead: UGent

WP3.3 RECRUITMENT AND SAMPLING

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

2 1 3 42

P/mnth inkind

4

BACKGROUND

Until now participants of 3 different age groups were recruited: newborns, adolescents and adults. In this cycle only adolescents will be recruited.

OBJECTIVES

To recruit a population of 600 adolescents, 14-15 years old, 3th year secondary school. Special attention will be paid to recruit adolescents of all social classes.

APPROACH

The program will start with a critical evaluation of the current protocol and to optimize the protocol in order to obtain a more sustainable and more efficient human biomonitoring framework of reference values which allows analysis of time trends and spatial trends. Costs and timing will receive major consideration. We will focus on the adolescent group. As in the previous campaigns students of the 3th year of secondary school, age 14-15 years old, will be selected. Adolescents can be recruited efficiently through schools. In each province a number of schools will be selected. We will take care to include schools from rural and urban areas. Participating students will be spread within Flanders according to the population density in the different provinces. When schools agree to participate, information letters and informed consents will be spread via the schools. Field work days will be planned in the schools. From each adolescent samples will be taken and questionnaires data will be collected. Attention will be paid to the recruitment of adolescents of all social classes, with emphasis on the lower social class, because we know from previous cycles that they are more difficult to persuade. To attain a representative Flemish study population we will focus on students in the BSO study types and students of a foreign origin. After some targeted consultations with field organisations and experts, and in close collaboration with the center, we will design and implement additional initiatives within the global recruitment strategy to better capture social and ethnic diversity in the study sample. Possible actions could include: tailored info sessions in classes (to stimulate supportive group participation) and the design of an appealing and translated info brochure for parents and adolescents). All the documents will be written in clear language, comprehensible for all the participants. Timing: start contact schools spring 2017, recruitment September 2017-2018. Samples : urine, blood, hair, questionnaires, cognitive tests

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Towards the end of the cycle all the participants will receive group and individual results of the analysis of the samples (see WP3.7), and where possible and feasible, the communication format of HBM results will be tailored to better meet the needs and barriers of social vulnerable subgroups (input from WP2.3). Also in the communication clear language will be used so everything is understandable for all the participants.

DELIVERABLES

- Recruitment brochure M17 - Contact schools M17 - Recruitment of 600 adolescents M20-M36 - Informed consent from the parents M20-M36 - Samples of blood, urine and hair on 600 adolescents. M20-M36 - Database with the names, addresses, school type and data from the questionnaires, M20-M36

PARTNERS

PIH, VITO, UAntwerpen Lead: PIH

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WP3.4 TOXICOLOGICAL ANALYSIS

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

10 2 2

P/mnth inkind

15 6 5

BACKGROUND

The last FLEHS cycle has provided information on the distribution of more than 50 biomarkers in the

Flemish population (see Table 3: ). Some of the exposure biomarkers have been followed throughout the three FLEHS campaigns (2002-2015). These results have been analysed and reported extensively [75,76]. The FLEHS campaigns have allowed to calculate reference values of biomarker levels for the specific age groups of the general population of Flanders. The data have been compared with available biomarker levels from international population surveys. The results have also been interpreted as to their significance for health by identifying the proportion of the population that was above internationally agreed health based guidance values. The combination of human biomonitoring data with information from the questionnaires has allowed to identify influential parameters for internal exposure levels [77]. These determinants are partly related to characteristics of the study participants, but also to the environmental and life style factors. In addition the exposure biomarkers have been associated with effect biomarkers and health information from the individual participants [78,79]. This has allowed to observe health related changes that are associated with the present levels of pollutants in the Flemish population. For the new proposal we have the ambition to continue the follow up and analyse the exposure trends in the Flemish population. We will select with higher priority the chemicals for which we 1) have not observed decreased biomarker concentrations over time (arsenic, thallium, PAHs), 2) chemicals for which we have not yet time reliable trends since they were measured only in FLEHS II and III and for which we observed associations with effect biomarkers or health outcomes (perfluorinated compounds, arsenic speciation, phthalates- manuscript in preparation). In addition we will select a number of priority chemicals and emerging chemicals that are of interest and are suspect of being influenced by the life style factors (use of space, eco-behaviour, energy efficient housing). The approach for the emerging chemicals is further developed in pillar 4 under the specific work package on “emerging chemicals” (WP4.4).

APPROACH

Based on the available information from the previous campaigns, based on criteria that were identified in the FLEHS III campaign (see Table 2) [6], based on the input from the consultations ( WP2.1) and taking into account the budgetary constraints, a final selection of exposure biomarkers will be proposed to the steering group for analysis. This selection will contain a list of chemicals to address time trends and a list of chemicals to address the relation between life style, environmental parameters and internal exposure and health with focus on the selected priority themes (see Table 3 and 4).

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Table 2: Selection criteria for chemical exposures included in the FLEHSII and III biomonitoring program

Criteria:

Health related criteria Chemical is legally managed (POPs convention, REACH,…) Effects known in humans/ animals/ in vitro Exposure : general population / specific sources Guidance values: external exposure/ internal exposure Bioaccumulation

Placental transfer Margin of safety < 5 Hazard

Technical aspects Biological matrix: invasiveness Estimated exposure versus limit of quantification Matrix volume needed Costs Preferred target population

The quality assurance is an important aspect of this work package. Before any analysis is granted to a laboratory, validation dossiers are requested describing in detail the SOP of the method, the limits of detection and quantification, details on accreditation, method validation and participation in ring trials, data on reproducibility, repeatability, accuracy and dynamic range. When collecting the samples during field work, the samples are collected or aliquoted in the optimal recipient for each analyte, taking into account the ideal storage conditions. On each day of field work, blank samples are collected in all different recipients to ensure no contamination occurs. Further, when the samples are being analysed by the different laboratories, whenever possible blinded samples will be co-processed such that results from previous campaigns can be compared with the new data allowing careful evaluation of the accuracy of the measurement. In FLEHS IV, time will be spend on creating a number of control samples that can then be used in future biomonitoring campaign without having to sacrifice valuable biobanking samples. VITO will invest 5 months of personnel time to aid in distributing the samples, coordinating the measurements and guaranteeing the quality of the obtained data.

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Table 3: overview of pollutants measured in FLEHS III

Newborns and their mothers Adolescents (14-15 year) Hotspot: Adolescents (14-15 year) Adults (50-65 year)

biomarkers of exposure - PRIORITY 1

individual measurements

- cord blood: heavy metals (As, Cd, Cr, Tl), persistent organic pollutants (POP’s) (PCBs, p,p’-DDE, HCB, Calux), perfluor compounds (PFOS, PFOA) - blood of the mother: / - hair of the mother: : (Me)Hg

- blood: heavy metals (As, Cd, Cr, Tl), persistent organic pollutants (POP’s) (PCBs, p,p’-DDE, HCB, Calux), - urine: toxicologically relevant As species; 1-OH-pyrene, t,t’-muconic acid, phthalate metabolites

- blood: heavy metals (As, Cd, Cr, Tl), persistent organic pollutants (POP’s) (PCBs, p,p’-DDE, HCB, Calux),

- urine: toxicologically relevant As species; 1-OH-pyrene, t,t’-muconic acid

- blood: persistent organic pollutants (POP’s)(PCBs, p,p’-DDE, HCB, Calux), perfluor compounds (PFOS, PFOA)

- urine: heavy metals (As, Cd, Cr, Hg, Tl), Triclosan, TBBPA, pesticiden (2,5-DCP, Pyrethroides, Organophosphate-pesticides

biomarkers of exposure - PRIORITY 2

individual measurements after accuracy confirmation in pooled samples

- cord blood: heavy metals (Ni, Cu, Mn), persistent organic pollutants (POP’s: HCH, Oxychlordane, Transnonachlor),

- blood: heavy metals (Ni, Cu, Mn), persistent organic pollutants (POP’s: HCH, Oxychlordane, Transnonachlor)

- blood: heavy metals (Ni, Cu, Mn), persistent organic pollutants (POP’s: HCH, Oxychlordane, Transnonachlor)

- blood: heavy metals (Ni, Cu, Mn), persistent organic pollutants (POP’s: HCH, Oxychlordane, Transnonachlor)

- Urine: heavy metals (Ni, Cu, Mn, Sb)

As = total arsenic; Cd = cadmium; Cr: chromium, Tl: thallium: PCBs = polychlorinatedbiphenyls; p,p’-DDE = dichlorodiphenyldichloro-ethane (metabolite from DDT); HCB = hexachlorobenzene; (Me)Hg = (methyl) mercury; TBBPA = tetrabromobisphenol A; PFOS = perfluoro-octanesulphonate; PFOA = perfluoro-octanic acid; 2,5 DCP 2,5-dichlorophenol; 2,4-D = Chlorophenoxy-pesticides; ETU = carbamate-pesticides

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Table 4: List of chemicals for which it is possible to address time trends in the FLEHS cycles

Overview of biomarkers for which time trends can be followed

FLEHSI FLEHSII FLEHSIII

Heavy metals cadmium (cord blood) newborns x x x

B-Cd adolescents x x x

B-Pb newborns x x x

B-Cd adolescents x x x

U- Cd adults 50-65 y x

x

arsenic(cord blood) newborns

x x

B-As adolescents x x

U-As adolescents x x

U-chroom adolescents

x x

Thallium (cord blood) newborns

x x

B-thallium adolescents

x x POPs (in serum) sum PCB138,153, 180 newborns x x x

adolescents x x x

adults 50-65 y x

x

DDE newborns x x x

adolescents x x x

adults 50-65 y x

x

HCB newborns x x x

adolescents x x x CALUX newborns x x x

adolescents x x x

PFOA newborns

x x

PFOS newborns

x x

Benzene U-t,t’-muconic acid adolescents x x x

PAH’s U-1 hydroxypyrene adolescents x x x

Phthalates U-DEHP adolescents

x x

U-MnBP adolescents

x x

DELIVERABLES

- Validation dossiers on toxicological analyses (M24) - Measurement data on the different toxicological analytes (M42)

PARTNERS

VUB, VITO, UHasselt, UAntwerpen Lead: VITO

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WP3.5 CONSTRUCTION OF DATABASE AND DATA ANALYSIS

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

1 8,5 2,4 6 4

P/mnth inkind

1

BACKGROUND

Until now the FLEHS studies have resulted in a database - which was made available in different software systems (Excel, Statistica, SAS, SPPS) - for each campaign containing the questionnaire data and toxicological data. For each dataset, an Excel codebook was established describing all the variables in the database. Recently also a collaboration has been established with the European Environment Agency (EEA) and the Joint Research Center (JRC) for access to data and protocols to serve information needs on HBM in Europe. Input was given for the management of data resulting from linking toxicological results and questionnaires in order to facilitate the inclusion of both existing and new HBM data into the Information Platform for Chemical Monitoring Data (IPCheM platform).

OBJECTIVES

To describe the different procedures needed for the data management of both the questionnaire and toxicological data. To obtain a database containing the questionnaire and toxicological data, and a codebook describing the variables in the database. To establish an sql-database which contains the results of the questionnaire data, the toxicological data, the information included in the codebook and the biobank data with information on the biospecimens. To construct a statistical analysis plan to conduct the statistical analyses needed to answer the research questions, including the socio-stratification of HBM-results (see WP 2.3).

APPROACH

Database management will be applied both for the questionnaire data as the toxicological data. Procedures for quality control (e.g. outliers, checking codes, etc.) will be constructed. Some questionnaire data may need recoding (e.g. grouping of categories) and some variables need to be calculated from the information available in the questionnaires (e.g. BMI). The different data sources will be merged into one database. A codebook will give an overview and explanation (variable name, description of the variable and score/unit) of the variables in this database. A sql-database will be constructed that contains both the results of the questionnaire data, the toxicological data, the information in the codebook, and the biobank data with information on the biospecimens (WP3.6). A statistical analysis plan will be constructed which specifies the key research questions and contains an explanation of the chosen statistical methodology. This statistical analysis plan is constructed in consensus with the FCC and should be approved by the Steering Committee. Database management and statistical analyses will be performed with SAS version 9.3 (SAS Institute Inc., Cary, NC, USA) and R/sql.

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DELIVERABLES

- Approved statistical analysis plan (M 18) - Database with questionnaire and toxicological analysis results (made available for the Flemish

Government and the promotors of the Flemish Center of Expertise on Environment and Health and transferable to IPCheM) (M60)

- Codebook describing the variables in the database (M50) - Sql-database linking the different data sources (M60) - Table with reference values and time trends (M48)

PARTNERS

UHasselt, VITO, VUB Lead: UHasselt

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WP3.6 BIOBANKING

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

3 4.5

P/mnth inkind

5

BACKGROUND

Generating a biobank for FLEHS studies allows to perform new measurements on participants with an already well-characterized environment and lifestyle profile, without having to collect new samples. The concept of the biobank may be considered as a biological archive of the current exposure levels in Flanders, and as such allows analysis of the past with future technologies. Since the campaign of FLEHSII, leftover biospecimens are stored as so-called biobanking samples. In FLEHSIII, a leftover volume was deliberately considered when writing down the protocols for sampling, meaning that for each participant additional sample volume was collected and stored for later analyses.

OBJECTIVES

To 1) store biospecimens of FLEHSIV participants for future analyses, 2) in a QC compliant system, and 3) to keep track of their biobank life cycle

APPROACH

For all different matrices collected, a considerate volume will be dedicated to biobanking in order to allow future analyses. The samples will be aliquoted with minimal required volumes for future analyses. The biobank lifecycle of each biospecimen (time of collection, pre-registration, receipt, processing, quality control (QC), storage management, request, retrieval, and distribution) will be registered and monitored using LIMS software. All will occur in compliance with the QC systems applying at VITO (ISO 9001 and 14001, OHSAS 18001). ‘Spelregels’ or ‘guiding rules’ are defined to guarantee the privacy and consent of the participants as well as the ethical approval. The LIMS database will be considered in the database management WP (3.5) in order to allow biobanking of both biospecimens as well digital data on all participants. VITO will invest post-doctoral knowledge (5M) to aid in organizing and maintaining the biobank.

DELIVERABLES

- QC compliant registration and storage database of remaining biospecimens collected in FLEHSIV (M48)

PARTNERS

VITO (aliquoting, registration, storage), PIH (aliquoting, collection of samples) Lead: VITO

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WP3.7 REPORTING

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

4 2 2 8 1

P/mnth inkind

0,2 2,5 1 1 1

The objectives of analyzing human biomonitoring data on environmental health include: assessing temporal exposure trends and the effectiveness of policy actions, characterizing patterns of exposure, comparing different population subgroups and identifying vulnerable subpopulations. Presenting and interpreting the data in a clear and understandable manner helps to broaden the outreach of the information. It also facilitates the use of a common “language,” or a more standardized approach, among different sectors involved in environmental public health policy-making. Advantages of using a standardized approach are consistency and comparability of data across various settings [80].

OBJECTIVES

To report data to participants and stakeholders after completing the different work packages (WP3.5; WP4.2; WP4.4) in accordance to the strategy described in WP 2.3. To publish a report providing summaries of temporal trends and a summary report on the behavioural determinants for the new emerging pollutants, the distribution of each biomarker within the population and reference values for the selected age groups. To publish at least 1 peer-reviewed manuscript outlining the major accomplishments, data gaps and priority environmental health issues based on the analyses of the new HBM data.

APPROACH

In order to inform all stakeholders on the data to be obtained in the different work packages, summary reports will be written, including key highlights and findings concerning determinants of exposure and exposure associated health effects, tables listing reference values and graphs presenting time trends. The ‘Executive Summary Reports’ on the Human Exposure to Environmental Chemicals published by the Centers for Disease Control and Prevention at the National Center for Environmental Health (US), the German Environmental Survey (GerES) reports published by the Health-related Environmental Monitoring department of the German Federal Environment Agency, and the reports of the Canadian Health Measures Survey (CHMS) published by Health Canada and the Public Health Agency of Canada will serve here as an example. Further, as was indicated in the evaluation of the previous cycles by external scientists, a strength of the program is broad dissemination of the results [24]. To this end, time will be dedicated to writing peer-reviewed manuscripts on the Flemish HBM data, both on the new HBM cycle as well as on data to be analysed in the follow up studies (WP4.3). The extent to which the latter will be performed depends on external sources of funding. New findings concerning influential exposure factors, exposure associated health effects as well as assessing temporal exposure trends and the effectiveness of policy actions will be written down in at least 1 scientific publication.

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At the level of the participants, attention will be given to develop a more digital and attractive platform for data communication. Work package 2.3 describes the necessary requisites for this process, such as tailoring of communication formats for more social vulnerable groups. Where possible and feasible, the communication format of HBM results to participants will be tailored to better meet the needs and barriers of social vulnerable subgroups.

DELIVERABLES

- A manuscript on analysis from data obtained in the follow up studies (M36; conditional as this depends on external funding),

- Updated facts sheets on the biomarkers containing hyperlinks to the FLEHS reports in which they are discussed

- A brochure for the participants containing their individual results at different stages in the project (M48),

- A summary report (in Flemish) with for each biomarker the distribution in the population and the reference values for the selected age group in the Flemish population (M48),

- A summary report in Flemish with the time trends (M48), - A manuscript with the main results (English) (M60).

PARTNERS

VITO, UAntwerpen, VUB, UHasselt, KUL, PIH Lead: VITO

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PILLAR 4: EXTERNAL EXPOSURE AND HEALTH

As society changes, new insights and approaches are needed. The work proposed in Pillars 2 and 3 builds on previous knowledge but the consortium has also identified new cross-cutting issues which will be addressed in this Research Pillar. The topics described in the different work packages will be touched upon in all scientific pillars and work packages. As was indicated by external scientists in the evaluation of the previous cycle, it would be recommendable to focus not only on harmful environmental exposure but also on its beneficiary health effects [24]. To this end, the research in Pillar 4 investigates the relation between space and health as well as the possible advantages of eco-behaviour on health and exposure.

WP4.1 SPACE AND HEALTH

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

1 18 1 2

P/mnth inkind

27.5 1 1 1

BACKGROUND

Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), mood and anxiety disorders, and conduct disorders are widespread in industrialized countries and importantly contribute to the total burden of disease during adulthood [81,82]. The development of the central nervous system starts during pregnancy and reaches maturity in adulthood. Therefore, the exposure to environmental factors during childhood and adolescence may play an important role in the development of neuropsychological disorders [83]. In this regard, contact with natural environments or green spaces may play a crucial role in the brain development [84,85]. To date, the relationship of neurobehavioral and/or cognitive development with green spaces during childhood has only been investigated in the frame of the Spanish BREATHE (brain development and air pollution in school children) project [86,87]. They reported reduced scores for ADHD and improved cognitive and behavioral development among children attending schools close to green areas and/or living close to green spaces. Green spaces provide children and adolescents opportunities for engagement, risk taking, discovery, creativity, mastery and control, strengthening sense of self and inspiring basic emotional states [84,85], In addition, they enhance psychological restoration [88], provide opportunities for physical activity [89,90], and influence the construction of social networks [91]. All these factors may impact positively on their cognitive development. Furthermore, the characteristics of the outdoor environment may influence the microbial environment which has an impact on the immune system and on mental health [92]. In addition, green spaces have a potential for improving outdoor air quality. In green areas the outdoor concentrations of traffic related air pollutants is reduced [93–96], and high concentrations of these outdoor air pollutants are associated with impaired neuropsychological development [97]. Moreover, proximity to certain green spaces such as agricultural areas may involve exposure to pesticides which are associated to impaired neuropsychological development and autism [98].

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Other potential mediators in the relationship between cognition and green spaces may be telomere length and the levels of cortisol [99,100]. Telomeres consist of TTAGGG tandem repeats and cap chromosomes [101]. They undergo progressive attrition in somatic cells because DNA polymerase is unable to fully replicate the ends of DNA caused by the unidirectional growth and the requirement for a primer to initiate synthesis [102]. As a result telomeres progressively shorten in somatic cells and a mean leukocyte telomere length has been observed to diminish with age [103,104]. In adults telomere length was observed to be strongly related to the telomere length at birth, which widely varied and showed synchrony with telomere length of different organs [105–107]. Previously, we showed that maternal residential proximity to traffic and lower residential surrounding greenness is associated with shorter placental telomere length at birth [108]. The interrelations between residential greenness, telomere length, cortisol levels and cognitive outcomes in adolescents have not been addressed so far.

OBJECTIVES

1. To investigate the relationship between the proximity to green spaces and cognition and behavior in adolescents. We will take the residential green space exposure over the life time (prenatal to adolescence) into account.

2. To investigate the interplay of potential important mediators such as cortisol and telomere length in the association between cognition and green space.

3. To link residential landscape variables to biomonitoring results including markers of exposure to traffic (e.g.: PAH’s, ‘t,’t-muconic acid) and pesticides to understand potential exposure differences which are associated with the residential environment.

4. To study the potential interplay of the biomonitoring results between green space and cognition.

5. The interrelation between green space and particulate air pollution on cognition.

APPROACH

Study design and study population For this WP data from 600 newly recruited adolescents will be combined with data from previous FLEHS III. Urine, blood nd hair samples will be collected from the newly recruited adolescents. If the budget and the load of the field work permit it, also saliva will be collected. In addition, they will undergo cognitive function tests, behavioural questionnaires and they will fill in questionnaires including basic health and socio-demographic questions, as well as questions on their perception of the environment. They will provide information on the current and previous home and school addresses, including the date of moving or changing schools, and on their usual commuting route from home to school. Green spaces: Residential and school addresses of adolescents will be geocoded over the life time. All GIS (Geographic Information System) analyses will be carried out using ArcGIS 10 software. Semi-natural-, forested -, and agricultural areas (greenness), residential and industrial areas in a 5000 m radius from the residential address were estimated based on Corine land cover (European Environment Agency). This will be repeated for 4000, 3000, 2000, 1000, 500, 300 and 100 m buffers. In addition, residential surrounding greenness will also be assessed using the Normalized Difference Vegetation Index (NDVI) based on Moderate Resolution Imaging Spectroradiometer (MODIS) images. NDVI is an indicator of greenness based on land surface reflectance of visible (red) and near-infrared parts of spectrum. Annual NDVI values were calculated for the year 2000 based on 10-day average measurements.

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Cognitive function and behavioural problems

Cognitive function: we will study three neurobehavioral domains: sustained attention and short-term memory, and manual motor speed. The sustained attention is assessed by continuous performance and Stroop test,[109] the short-term memory by the digit span forward and backward and the motor speed by finger a finger tapping task.

Behavioral problems will be assessed using the Strengths and Difficulties Questionnaire (SDQ): The SDQ [110,111] is an internationally disseminated and validated screening questionnaire to assess mental and behavioural strengths and difficulties in 3- to 16-year-olds. The dimensions “emotional symptoms”, “conduct problems”, “hyperactivity/ inattention”, “peer relationship problems” and “prosocial behaviour” are measured by five SDQ items each, resulting in 25 items total are rated on a three-point scale.

Potential confounders or effect modifiers We will consider environmental factors/pollutants from outdoors. Interpolated background levels of PM10, PM2.5 and NO2 will be combined with measurements of traffic density and distance to major roads. Distances to the nearest major road with traffic counts available and traffic density were determined using GIS functions (ArcGIS 10 software). We will collect information on two traffic indicators at the mother’s residence, i.e., distance to major road and traffic density. Traffic density within a 200 m radius (buffer) from the residence will be defined as the length of each road in this buffer multiplied with the traffic count on each specific road. This will be calculated for a 200 m buffer in steps of 10 m. Traffic counts are obtained from the Traffic Center Flanders, Department of Mobility and Public Works. In addition, we will administer questionnaires to collect information on the personal perception of the environment, parental socio economic position (education and occupation) and the adolescent socio-demographic and health condition. Biochemical and molecular markers

- Telomere measures We use a quantitative qPCR method to measure relative telomere length (log T/S ratio). The method has been validated. The method has been evaluated in an inter-laboratory validation exercise. The method has been applied in previous FLESHIII cohort.

- Cortisol Hair samples will be collected as close as possible to the scalp and analyzed for cortisol as an indicator for stress exposure.

DELIVERABLES

- Selection of cognitive tests and questionnaires (M4) - GIS greens space calculations for new and previous FLEHS cohorts (M12-48) - Construction of the database (M49) - Integration with biomonitoring results (M50) - Statistical analysis and data interpretation (M50-60)

PARTNERS

UHasselt, VITO, VUB, UAntwerpen, UGent, KUL Lead: UH

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WP4.2 ECO-BEHAVIOUR AND EXPOSURE

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

1 3 5 2

P/mnth inkind

2 1

BACKGROUND

In a survey of more than 10 000 households in 10 countries (Australia, Canada, the Czech Republic, France, Italy, Korea, Mexico, the Netherlands, Norway and Sweden) the OECD looked at factors that affect people’s behaviour towards the environment in 5 specific areas: 1. water use, 2. energy use, 3. personal transport choices, 4. organic food consumption, 5. waste generation and recycling. Recently, studies indicate that there may be a relation between ecological behaviour in these area’s (e.g. living in energy-efficient houses, buying environmentally friendly products, buying organic foods, vegetarian diet, …) and (1) the exposure to environmental contaminants as well as (2) certain health effects. For example, a recent Norwegian study found that consumption of organically produced foods during pregnancy was associated with a lower prevalence of hypospadias in the male off-spring, which may be induced by in utero exposure to endocrine disrupting chemicals [112]. A second examples is the study of Serrano et al., investigating whether reported use of ecofriendly and chemical-free products was associated with lower phthalate biomarker levels in comparison to not following such practices [113]. They found that women who reported rarely/never purchasing ecofriendly, chemical-free and environmentally friendly personal care (PCP) and household products had higher levels of monoethyl phthalate (MEP) compared to always/often respondents. Sometimes following these practices were associated with monoisobutyl phthalate (MiBP) levels that were about 18% lower as compared to always/usually respondents. They observed trends for increasing concentrations of MEP with decreasing frequency of purchasing ecofriendly PCPs (p = 0.01) or house products (p = 0.03). Regarding the diet, reports of rarely/never eating food that is organic, ecofriendly, environmentally-friendly or chemical-free were related to lower MEP levels as compared to always/usually following this practice. Lastly, rarely or never eating food marked “organic”, “pesticide-free”, or “chemical-free” during pregnancy was associated with sum of Di-2-ethylhexyl phthalate(DEHP) metabolite levels that were lower in comparison to those in the always/usually category [113]. Therefore, associations in both direction were found and both studies indicated that future investigations are needed to clarify the role of consumer product choices in relation to contaminant exposure and health effects. Another interesting issue, related to eco-behaviour, is the potential public health impacts of changes to indoor air quality and temperature due to major changes in housing to improve energy efficiency (see figure). A recent study published in BMJ, assessed the health effects of home energy efficiency intervention in England [114]. Hamilton et al. concluded that energy efficiency retrofits in housing can improve health by reducing exposure to cold and air pollutants if these retrofits are properly implemented alongside ventilation. They referred to mental health, respiratory health, cardiovascular health, etc. Nevertheless, they stressed that maximising the health benefits requires careful understanding of the balance of changes in pollutant exposures, highlighting the importance of ventilation to mitigate the risk of poor indoor air quality [114].

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Figure 2: Connections between energy efficiency in housing and health (adapted from Hamilton et al., 2015) (GHG: greenhouse gas; STS: second-hand tobacco smoke; VOC: volatile organic compound)

OBJECTIVES

It is of interest to investigate also in the Flemish population whether associations exist between certain ecological behaviour (including healthy consumer-behaviour: buying environmentally friendly products, consuming organic food and living in energy efficient houses) and exposure to environmental contaminants (and maybe also related health effects). To this end, 3 research questions will be answered:

1) How can eco-behaviour be defined in Flanders? 2) Does eco-behaviour affect the internal exposure level? 3) Is eco-behaviour associated with better health parameters?

APPROACH

The 5 areas in which the OECD defined factors that could affect the behaviour of people towards the environment can be translated to 3 domains of interest within the FLEHS campaigns: 1) Energy-efficient houses: water use, energy use, 2) Food consumption, 3) Waste generation and recycling. 4) Personal transport: car vs public transport / bike / car-pooling, A first onset for this investigation can be started already in the first year using data of FLEHSIII, more specifically data of the adults as well as of the mothers-newborns. In both cycles of FLEHSIII, the questionnaire included a question on whether they buy biological and/or ecological products and if so, they were asked to indicate the frequency by a percentage. Also a question on the type of ventilation in the house and frequency of ventilating the house was included. Therefore, these data can be used to investigate whether associations exist with the measured biomarkers in both campaigns.

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Also in the new cycle, it is the purpose to collect data on ecological behaviour of the adolescents and their parents and to look for relations with biomarkers of exposure and effect in. To this end, questionnaires will be designed to attribute different eco-behaving profiles to the participants. It will be investigated to what extent these profiles are related to other characteristics such as SES, urbanization, … For each of the OECD-defined areas, typical exposure sources and expected health effects will be attributed (Exposure sources: Passive housing: exposure: bacteria, (SVOCs)--phthalates, polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and pesticides, other emerging chemicals; Personal transport: air pollution; Food consumption: organic food, local food: mostly pesticide exposure; Waste generation and recycling: chemicals in cleaning products). Furthermore, the link with current policy strategies and intentions will be made. Data available from the past FLEHS cycles will indicate whether it is favourable to investigate the above research questions in the overall cohort or in a case-control setting.

DELIVERABLES

- Summary report describing different social profiles on eco-behaviour in Flanders (M30) - Manuscript on the association between eco-behaviour and internal chemical exposure and/or

on the association between eco-behaviour and health effects (M60)

PARTNERS

UAntwerpen, UGent, VITO, PIH Lead: UGent

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WP4.3 FOLLOW UP STUDIES

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

5 2 2 2 2

P/mnth inkind

1 1 4

BACKGROUND

As this proposal is directed towards a fourth FLEHS campaign, a lot of effort has been done during the past years to establish a framework (protocol) for follow-up of the populations that were part of the previous campaigns. Consent of all participants was requested for follow up through health databases such as ‘Kind & Gezin’, ‘Centrum voor Leerlingenbegeleiding’ and ‘Intermutualistisch Agentschap (IMA)’. Besides their internal exposure status at the moment of the human biomonitoring investigation, we also archived their external burden of exposure through completing databases on exposure to particulate matter (PM10 and PM2.5), ozone, black carbon and noise (Irceline, dienst Milieuhinder, departement Leefmilieu, Natuur en Energie van de Vlaamse overheid).

OBJECTIVES

This Flemish database and biobank of about 1800 newborns and their mothers, 2200 adolescents (14-15 year-old) and 1600 adults (200 20-40 and 1400 +50 years old) allows identification of biomarkers as early warning signals for development of disease in a later stage of life. As exposure through environmental and lifestyle is so well characterized in the past FLEHS campaigns, this database offers a unique prospect to identify risk factors for disease development and therefore the opportunity to intervene and intervene, or make the first steps towards a Flemish preventive medicine concept.

APPROACH

Based on the existing FLEHS database different interesting research hypotheses could be explored within the context of follow up studies. For instance, the newborns of FLEHSI have reached the stage of peripuberty and as we have consent to retrieve health data on this period in life, prenatal exposure could be associated. Further, the adolescents of FLEHS I are now starting to reach the stage of fertile age and may have children of their own. The concept ‘children of the children’ would allow to investigate transgenerational effect of environmental exposure, a concept that is important in the context of endocrine disruption. Besides the existing FLEHS databases, 3 new birth cohorts will be considered in the FLEHS consortium: 1) 3xG, a rural mother-child cohort (n=300) in the communities of Dessel, Mol and Retie; 2) IPANEMA, an urban cohort (n=200) in Antwerp, and 3) ) ENVIRONAGE (n=950). The data obtained in these cohorts will add to the FLEHS knowledge base and biobanking samples could be used for complementary analyses. Questionnaires of 3xG and IPANEMA are similar to those in FLEHS. Follow-up of 3xG and ENVIRONAGE children is foreseen in the respective projects. VITO invests 4 months of doctoral training in the research of this WP.

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DELIVERABLES

- Association between development of puberty in FLEHSI newborns and prenatal exposure to POP’s and heavy metals (M 36)

Further topics are dependent of external funding

PARTNERS

UHasselt, VITO, UAntwerpen, PIH Lead: VITO

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WP4.4 EMERGING CHEMICALS

Participant short name:

UAntwerpen KUL UHasselt UGent VUB VITO PIH

P/mnth on project budget

5 3

P/mnth inkind

5

BACKGROUND

Emerging chemicals are, as the name indicates, chemicals that are currently introduced to substitute known harmful chemicals in consumer products that are widely used by the general population, such as plastics, food contact materials, personal care products, household products, furniture, etc. Human biomonitoring aims at detecting the presence of such emerging chemicals in the wider population. This is of interest also in the context of chemicals policy, as it is a tool to explore when new exposures are frequent enough to show up in the general population [116].

OBJECTIVES

1) We will collect information on internal exposure to a range of emerging chemicals in Flemish adolescents based on the assumption that they are present in consumer products that are widely used in the population, 2) We aim for identification of metabolites/parent emerging chemicals and their metabolites by using an array of analytical approaches, such as A) untargeted screening, B) suspect screening of emerging chemicals and their metabolites, C) targeted measurements of emerging chemicals and/or their metabolites identified by pct A and B. 3) We will identify life style-specific exposure profiles: compounds that may differ in relation to specific behavioural patterns. This activity allows evaluation of differences between common lifestyle and behaviour and the more alternative “eco-behaviours” mentioned in WP4.2, such as: living in energy efficient houses, organic food consumption, consumption of local food, avoiding plastic food packaging, or preferential use of environmental friendly products (e.g. cleaning/disinfectants and personal care products). This should give guidance towards more accurate prevention measures that protect against exposure to ubiquitous environmental toxicants and their substitutes in new materials.

APROACH

As measured and well-documented in the previous FLEHS cycles (see Tables 3 and 4), targeted analyses of priority compounds will still be performed in this FLEHS cycle. However, several approaches will be used to identify exposures to emerging chemicals. Table 5 below lists a wide range of emerging chemicals which have been recently reported in the literature and are compounds of interest also for FLESH. An effort will be made to include chemicals of concern which were sporadically measured in the previous FLEHS surveys, such as flame retardants, plasticizers and to expand the range to their current substitutes.

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The untargeted and suspect screening of emerging chemicals and their metabolites will be performed on a limited amount of e.g. pooled samples (from different individuals) in a first pilot study approach. In some cases, especially when there are considerable diurnal variations expected, repeatedly taken samples from the same donor will be analysed to assess within and across day variability. The untargeted/suspect screening of emerging chemicals should add to the classical way of performing targeted analysis of known contaminants and will allow to perform a more complete mixture-like assessment of the internal exposure. If the sensitivity allows detection and quantification, we will measure by targeted analyses the profile of emerging chemicals and/or their metabolites in a subset of adolescents of the FLEHS-IV survey. The sparsity of data on the normal variation in the population across the measureable/detected metabolites limits a priori power calculations. The sample size and study design needed will be assessed based on the pilot measurements of the pooled and individual samples. A final selection of the ‘emerging chemicals’ will be made after input from steering group and stakeholders (see WP2.1). This selection will be based on the literature information related to the use of chemicals, their applications and eventually their previous reporting in human matrices. Each method for biomarker analysis will be documented with respect to method characteristics and chemical validation (as is described in WP.3.4 but with adjusted criteria for ‘suspect screening’). Closely related, the measurement of the ubiquity, diversity and functions of small molecules that can be detected in urine, blood sample, hair or even exhaled air, represents an important way to link individual exposures, genetics and phenotype [115]. Using the metabolomics approach, an emerging field that potentially can aid in the identification of exposure profiles, we expect to assess the profiles of many biomarkers in at least 200 adolescents. The data will be statistically analysed in close collaboration with WP3.5 to assess patterns and perform screening of compounds, intra and inter individual variability (via Intra Class Correlation, ICC). By oversampling on the study population of all 600 adolescents, a case control set-up will worked out such that variables will be identified that may influence the exposure route, a.o. personal characteristics, environmental and lifestyle variables, food consumption. Table 5: Table 6: Emerging chemicals which have been recently reported in the literature and that are possible of interest for FLEHS-IV.

Themes Compound group of interest

Priority chemical Targeted

Emerging compounds Targeted and forensic

screening

References for emerging

compounds

Avoiding plastic food packaging

Plasticizers and their substitutes Plastic additives

Phthalates BPA

Metabolites of other plasticizers (e.g. DINCH*) in urine BPS, BPF

Schütze et al., (2014) [116]; Fromme et al. (2015) [117] Ye et al. (2015) [118]

Organic food consumption

Pesticides Pyrethroids Glyphosate

/ /

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Themes Compound group of interest

Priority chemical Targeted

Emerging compounds Targeted and forensic

screening

References for emerging

compounds

Consumption of locally grown foods such as eggs and vegetables

Organochlorine pesticides Heavy metals PCDDs/PCDFs and PCBs

DDE Hg, Cd, Cr, Pb, Tl DR-CALUX, PCBs

/ / /

/ / /

Use of environmental friendly products

Parabens Siloxanes Fragrances

Ethyl-, butyl, phenyl-paraben Siloxanes

/ Cyclic volatile methyl siloxanes Natural fragrances screening

/ Fromme et al. (2015) [117] /

Living in energy efficient houses

Flame retardants + substitutes Perfluorinated compounds

Organophosphate flame retardants (OPFR) PFOS, PFOA

Metabolites of OPFR Dechlorane Plus and new brominated FRs in serum Other perflorinated compounds (acids, sulfonates) to reflect the current use of PFCs

Van den Eede et al. (2015) [119]; Dodson et al. (2014) [120]; Cequier et al. (2015) [121]; Fromme et al. (2015) [117]

*DINCH: diisononylcyclohexane-1,2-dicarboxylate; non-aromatic plasticizer and phthalate substitute

DELIVERABLES

- Final selection of the biomarkers (M12) - Validation documents with characteristics and performance of the emerging chemicals

biomarker analysis (M24) - Distribution of the biomarker levels in the study population (M54) - Manuscript on methodology and environmental, personal and life style characteristics that

influence the exposure levels in the study population(M60)

PARTNERS

UAntwerpen, VUB, VITO Lead: UAntwerpen (Covaci)

60

3. TIME TABLES 2016-2020 (PERSONEELSINZET PER WP TO BE INCLUDED)

Personeelsinzet (in persoonsmaanden) 2016 2017 2018 2019 2020 Totaal

Directe personeelsinzet 53,60 51,50 52,30 52,60 50,40 260,40

WP 1: Coördinatie 2,00 1,00 1,00 1,00 1,00 6,00

WP 2: Science Policy 15,00 9,00 8,50 9,50 14,00 56,00

WP2.1 cross-cutting consultation on HBM 13,00 1,00 0,00 0,00 0,00 14,00

WP2.2 science - policy translation 1,00 2,00 2,00 4,00 12,00 21,00

WP2.3 communication and social inclusion 1,00 6,00 6,50 5,50 2,00 21,00

WP 3: HBM Platform 28,30 30,70 29,10 28,80 27,50 144,40

WP3.1 study design 9,50 5,40 2,30 1,40 1,40 20,00

WP3.2 questionnaires 3,90 6,90 2,40 1,40 1,40 16,00

WP3.3 recruitment and sampling 8,40 11,40 11,40 8,40 8,40 48,00

WP3.4 toxicological analysis 2,00 2,50 4,50 2,50 2,50 14,00

WP3.5 database and data analysis 1,30 1,80 3,80 8,90 6,10 21,90

WP3.6 biobanking 3,00 1,00 1,50 1,00 1,00 7,50

WP3.7 reporting 0,20 1,70 3,20 5,20 6,70 17,00

WP 4: Exposure health 8,30 10,80 13,70 13,30 7,90 54,00

WP4.1 space and health 0,00 5,00 5,50 6,00 5,50 22,00

WP4.2 ecobehaviour 1,40 2,90 3,90 2,40 0,40 11,00

WP4.3 follow up studies 4,90 1,40 2,80 2,90 1,00 13,00

WP4.4 emerging chemicals 2,00 1,50 1,50 2,00 1,00 8,00

Totaal aantal persoonsmaanden 53,60 51,50 52,30 52,60 50,40 260,40 The planned working time for the short-term assignments is in total 5 %.

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4. GANTT CHART

2016 2017 2018 2019 2020 Deliverables

WP 1 - Coordination

Minutes of the executive committee meetings (4 x per year); Annual work plans (M12,24,36,48,60); Annual reports with publication lists and lists of the reports that are produced (M 12, 24, 36, 48, 60); Signed agreements on exchange with the European Human Biomonitoring Initiative (M12); Signed agreements with other projects to exchange data, samples and multiply efforts (M48)

WP

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Sci

ence

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2.1 Cross-cutting (policy) consultation on HBM

The reports of parallel thematic round tables (M12), with a focus on the cross-cutting themes proposed in this research proposal: (incl. identification of opportunities for the upcoming HBM-campaigns and policy integration in general): Use of open space and health, Eco-behaviour and healthy housing, - Emerging chemicals.

2.2 Science - policy translation

Development of process architecture for the implementation of the phased action plan, following the communication of a new cycle of HBM-results (2019-2020), including relevant evaluation criteria, based on the evaluation framework developed during the previous cycle of the Center (M44); Implementation and intermediary reporting of phase I and II (in cooperation between the research team and the contracting government) (M60); Paper on perspectives for evaluation of the phased action plan (M48).

2.3 Risk communication and social inclusion

‘Spelregels’ (Guiding rules) (M12); Communication plan(s) (M48); Peer-reviewed paper on risk communication strategy (M48); Adapted recruitment strategy and actions for social and ethnic diversity (M18); Peer-reviewed paper on socio-stratified HBM results (M60)

WP

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Hu

man

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pla

tfo

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3.1 Study design

Selection of biomarkers, sampling matrix for analysis (M6, M18); Study protocol for time trends (M12), for emerging chemicals reference values (M 18), for study on exposure to eco-behaviour related life style factors (M18), and for study of exposure and health in relation to proximity and accessibility to blue/grey/green/agricultural spaces (M18); Approval from ethical committees (M 18); Authorisation from the Flemish Supervisory Committee for Electronic Administrative Data Flows (M18)

3.2 Questionnaires

Digital platform to interview the participants (M18); Paper questionnaires (M18); Database with archived questions (M36); Database containing information on exposure routes, influential factors and specific health effects of each participant (M48)

3.3 Recruitment and sampling

Recruitment brochure (M17); Contact schools (M17); Recruitment of 600 adolescents (M20-M36); Informed consent from the parents (M20-M36); Samples of blood, urine and hair on 600 adolescents (M20-M36); Database with the names, addresses, school type and data from the questionnaires (M20-M36)

3.4 Toxicological analysis

Validation dossiers on toxicological analyses (M24); Measurement data on the different toxicological analytes (M42)

3.5 Construction of database and data analysis

Approved statistical analysis plan (M 18); Database with questionnaire and toxicological analysis results (made available for the Flemish Government and the promotors of the Flemish Center of Expertise on Environment and Health and transferable to IPCheM) (M60); Codebook describing the variables in the database (M50); Sql-database linking the different data sources (M60); Table with reference values and time trends (M48)

3.6 Biobanking

QC compliant registration and storage database of remaining biospecimens collected in FLEHSIV (M48)

3.7 Reporting

Brochure for the participants containing their individual results at different stages in the project (M48); Summary report (in Flemish) with for each biomarker the distribution in the population and the reference values for the selected age group in the Flemish population (M48); Summary report in Flemish with the time trends (M48); Manuscript with the main results (English) (M60).

WP

4 -

Ext

ern

al e

xpo

sure

an

d h

eal

th

4.1 Space and health

Selection of cognitive tests and questionaires (M4); GIS greens space calculations for new and previous FLEHS cohorts (M12-48); Construction of the database (M49); Integration with biomonitoring results (M50); Statistical analysis and data interpretation (M50-60)

4.2 Eco-behaviour and exposure

Summary report describing different social profiles on eco-behaviour in Flanders (M30); Manuscript on the association between eco-behaviour and internal chemical exposure and/or on the association between eco-behaviour and health effects (M60)

4.3 Follow up studies

Association between development of puberty in FLEHSI newborns and prenatal exposure to POP’s and heavy metals (M 36)

4.4 Emerging chemicals

Final selection of the biomarkers (M12); Validation documents with characteristics and performance of the emerging chemicals biomarker analysis (M24); Distribution of the biomarker levels in the study population (M54); Manuscript on methodology and environmental, personal and life style characteristics that influence the exposure levels in the study population(M60)

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5. UNLOCKING KNOWLEDGE

EXTERNAL INFORMATION AND COMMUNICATION

External communication of results of the study to the public is strictly regulated by a mutual agreement between the Center of Expertise for Environment and Health and the responsible ministers and their administrations. External communication will be first agreed by the executive committee. Scientific valorization just needs to be announced timely in advance to the Steering group. The guideline governing external communication is the document “Spelregels”, that will be developed in the first months of 2016 and will be discussed with the Flemish government. The following instruments will be used for external messages and communications:

a) An informative website (in cooperation with the Flemish administrative authority) will inform about the aims, activities, reports and publications of the center.

b) A brochure of the results of the different biomonitoring studies for extended distribution. c) An e-letter similar to “Environment and Health” (Gezond Milieu), for which input will be

delivered by the center but cooperation is requested with the Flemish LNE Department for final editing and dispatching.

The executive committee will develop a systematic interaction with relevant other centers of policy relevant research. Priorities will also be set with the agreements, made in Pilar 2 – Science-Policy interface, on the ex ante consultation of the relevant policy field actors.

PUBLIC COMMUNICATION

Public communication as a result of the research activities of the center can only occur after approval by the responsible ministers, who are assisted by the steering committee. All documents concerning public communication of the center must be delivered at least 5 weeks before the scheduled communication to the responsible ministers via the steering committee. If the ministers do not respond within two weeks, the steering committee has one week to announce its decision on the approval of the communication to the center. (Based on the Management Agreement) The message must be checked (“getoetst”), be clear and reflect the knowledge of the target group for whom the message is intended to. Also, the message is well structured, engaging and interactively adapted to the language of the target group. During the public presentation of the research results they are interpreted according to their (public) health significance. Risk Equations (relative height / low of the risk) are then used, in function of a careful clarification of the meaning. In this way, special attention will be given to various health perspectives and differences of perception in different types of risks.

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If the steering committee indicates that the above agreements are not or insufficiently fulfilled, the steering group can instruct the center to adapt the communication plan and / or protocol and decide to postpone the communication until it meets the made agreements adequately. The center will also present its research results firstly to the medical environmental experts at the Logos (MMK’s) before they will be communicated externally.

PUBLICATIONS AND ACTIVE DISTRIBUTION OF INFORMATION TO A BROAD PUBLIC

The researchers of the center have the right to publish their results and concepts resulting from the research financed by the Flemish Government as part of the Flemish Center for Environment and Health. Where for manuscripts and scientific valorization the default language is English, overviews of the study results and executive summaries will be provided in Dutch. These publications, however, have first to be presented to the responsible Minister(s) who can delay the submission of the publication by three months, starting from the day the Cabinet received the publication. Press conferences, press releases and other active communication to a broad public will always be organized by the center in co-operation with the responsible Minister(s) via the steering group. Prior to public dissemination, results will be presented to the steering group and the responsible ministers. - Individual researchers have the right – within the context of the academic freedom - to give their

own opinion about the research results or insights to the public, but need to inform the steering group and responsible Minister(s) about the content of their communications. The Minister can enforce a moratorium of three months.

- In collaboration with the steering Group and the responsible Minister(s), the center enhances public awareness by announcing and publishing research activities in an accessible way on the website of the center.

AUTHORSHIP OF PUBLICATIONS

Concerning the authorship of publications two items are of special importance. First, the publishing of scientific articles needs to be encouraged and made easier. Second, the legitimate interests of the concerned scientist must be safeguarded. The following procedure needs to be followed: 1. When a researcher of the center wishes to write an article that contains data which were generated

within the framework of the center, he/she needs to present a short description and a list of authors (from within or outside the center) to the executive committee. With regard to the biomonitoring especially a small group of researchers will be composed within the framework of the field coordinators committee, who will write an article together. As first author acts the researcher who writes the larger part of the article. Coauthors can also be scientists who do not belong to the Flemish Center of Expertise on Environment and Health. The coordinator of the FCC needs to present to the executive committee a short description of the article and a list of authors.

2. The application will be formally presented at the meeting of the executive committee. The executive committee takes the final decision concerning the authorship and co-authorship and motivates this decision to the applicant of the field coordinators committee.

3. The authors are responsible for the content of the article. 4. Each publication will be presented to the executive committee and will be announced to the

steering group.

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5. This procedure does not need to be followed in case of abstracts and publications in other than scientific or professional magazines or books. However the involved texts will be presented to the steering group.

6. The acknowledgement is the following: “The study was commissioned, financed and steered by the Flemish government (Department of Environment, Nature and Energy)”.

7. If data were produced and for concepts developed by financial support allocated by the Flemish Government to the center, the financial source must be clearly announced in the publication.

FOREGROUND KNOWLEDGE - OWNERSHIP AND USER RIGHTS

The Foreground Knowledge will be owned by the initiating institutions (Initiators) as defined in the “Samenwerkingsovereenkomst”. User rights will be granted to the Flemish Government in accordance with the conditions as defined in the “Samenwerkingsovereenkomst”. Notwithstanding the above-mentioned, the parties agree that the collected data, results and knowledge of the biomonitoring program will be co-owned by the participating institutions and their partners, represented by the promotors Prof. Willy Baeyens and Martine Leermakers, Prof. Benoit Nemery de Bellevaux, Prof. Ilse Loots, Prof. Nawrot, Prof. Greet Schoeters, Prof. Adrian Covaci, Prof. Vera Nelen and Prof. Stefaan De Henauw. These results are entirely and permanently at the disposal of the initiating institutions, their partners and the Flemish Government. Use of the data should be always in respect of the guidelines concerning privacy and ethics. During the research program and also after 2020, the Flemish government has permanent, free, complete and unlimited user rights of the data and the results of the human biomonitoring program. A copy of the datasets of the human biomonitoring will at the end of the agreement, end 2020, be transferred to the “opdrachtgever”, the administration(s) of the involved minister(s). Commercializing of data of the humane biomonitoring program by any participant, partner, promotor or third approved user is strictly forbidden.

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6. INTERACTION WITH THE FLEMISH AUTHORITIES

The interaction with the Flemish authorities is governed by the consortium agreement. Specific aspects will be included in the guiding rules that will be drafted in the first months of the consortium. Involvement and interaction of the authorities in knowledge disclosure and dissemination of results are treated in the section above. The program is participatory designed and aims to involve authorities in the different steps of the program from problem formulation, over study design to interpretation of results. The scientific interpretation will be performed by the consortium but various perspectives including the perspective of the authorities will be taken into account for creating knowledge. Use of the study results for policy support remains the role of the policy makers, but better understanding of the policy questions by the scientists and of the study outcomes by the policy makers and administrators will be stimulated throughout the program. Representatives of the administration will be invited to attend the monthly field committee meetings and reporting at the steering groups will provide a forum for interaction and exchange between scientists and policy makers. The center will provide access to the study results in line with ethical and privacy requirements, the management agreement and the guiding rules for communication.

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7. QUALITY ASSURANCE

The quality assurance method adopted for all activities of the Flemish Center of Expertise for Environment and Health is based in the first place on the research plan itself: it is important that the proposal is written and structured in a very clear way. The responsibilities and tasks of the participating research groups are well defined in the project. The following tasks will be executed:

Establishing the critical points of the projects and the subprojects in collaboration with the research leaders and scientists;

Verifying those critical points by using a control program;

Reporting possible aberrations to the research leaders and the management;

Approving the research report by means of a QA-statement. The promoters and partners are responsible for the elaboration of a clear research program including the “mile stones” and the intermediate evaluation of the research plan. In order to guarantee the quality of the research plan measures are taken to manage and to control the complete “primary process”. The primary process starts with preparation and ends with reporting of the results. At each step or level, a number of quality aspects have to be dealt with: Preparation

Sample size calculations

Recruitment plan

Inclusion and exclusion criteria Sampling, transport and storage samples

Sampling plan with instructions to collect samples in a representative and statistically correct way

Sample identification

Manner of packaging and measures preventing (cross-) contamination

Conservation conditions and periods, taking into account the stability of the sample

Measures preventing loss, contamination Analyses

Method validation (accuracy, reproducibility, matrix effects, linearity, LOD, LOQ, robustness)

Quality control: first line control and the use of control charts

Use of certified reference materials

Ring tests Data Treatment

Statistical method design

Verification of raw data and calculations, preferentially by an independent person

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Reporting

Defining the internal and external communication lines and the way to elaborate, to verify and to approve intermediate reports

Verification of the content of a report

Approval by two senior experts of the consortium before final submission

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8. BUDGET

UA Universiteit Antwerpen KUL Katholieke Universiteit Leuven UH Universiteit Hasselt UG Universiteit Gent VUB Vrije Universiteit Brussel VITO Vlaamse Instelling voor Technologisch Onderzoek PIH Provinciaal Instituut voor Hygiëne

GLOBAL BUDGET PER PARTNER

Promotor 2016 2017 2018 2019 2020 TOTAAL

Ilse Loots, Greet Schoeters, Adrian Covaci (UA) 216.100,00€ 135.800,00€ 135.800,00€ 135.800,00€ 142.125,00€ 765.625,00€

Benoit Nemery de Bellevaux (KUL) -€ 25.987,50€ 25.987,50€ 25.987,50€ 25.987,50€ 103.950,00€

Tim Nawrot (UH) 23.100,00€ 49.087,50€ 49.087,50€ 49.087,50€ 49.087,50€ 219.450,00€

Stefaan Dehenauw (UG) 11.550,00€ 28.875,00€ 28.875,00€ 28.875,00€ 11.550,00€ 109.725,00€

Willy Baeyens, Martine Leermakers (VUB) 33.000,00€ 44.000,00€ 44.000,00€ 44.000,00€ 55.000,00€ 220.000,00€

Greet Schoeters (VITO) 132.000,00€ 132.000,00€ 132.000,00€ 132.000,00€ 132.000,00€ 660.000,00€

Vera Nelen (PIH) 89.250,00€ 89.250,00€ 89.250,00€ 89.250,00€ 89.250,00€ 446.250,00€

TOTAAL 505.000,00€ 505.000,00€ 505.000,00€ 505.000,00€ 505.000,00€ 2.525.000,00€

Promotor 2016 2017 2018 2019 2020 TOTAAL

Ilse Loots, Greet Schoeters, Adrian Covaci (UA) Ilse Loots 98.175,00€ 98.175,00€ 98.175,00€ 98.175,00€ 98.175,00€ 490.875,00€

Greet Schoeters 88.935,00€ -€ -€ -€ -€ 88.935,00€

Adrian Covaci 28.990,00€ 37.625,00€ 37.625,00€ 37.625,00€ 43.950,00€ 185.815,00€

Benoit Nemery de Bellevaux (KUL) 25.987,50€ 25.987,50€ 25.987,50€ 25.987,50€ 103.950,00€

Tim Nawrot (UH) Tim Nawrot 25.987,50€ 25.987,50€ 25.987,50€ 25.987,50€ 103.950,00€

Liesbeth Bruckers 23.100,00€ 23.100,00€ 23.100,00€ 23.100,00€ 23.100,00€ 115.500,00€

Stefaan Dehenauw (UG) 11.550,00€ 28.875,00€ 28.875,00€ 28.875,00€ 11.550,00€ 109.725,00€

Willy Baeyens, Martine Leermakers (VUB) 33.000,00€ 44.000,00€ 44.000,00€ 44.000,00€ 55.000,00€ 220.000,00€

Greet Schoeters (VITO) 132.000,00€ 132.000,00€ 132.000,00€ 132.000,00€ 132.000,00€ 660.000,00€

Vera Nelen (PIH) 89.250,00€ 89.250,00€ 89.250,00€ 89.250,00€ 89.250,00€ 446.250,00€

TOTAAL 505.000,00€ 505.000,00€ 505.000,00€ 505.000,00€ 505.000,00€ 2.525.000,00€

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GLOBAL BUDGET PER COST CATEGORY

2016 2017 2018 2019 2020

Inkomst: Financiering Vlaamse

overheid € 505.000,00 € 505.000,00 € 505.000,00 € 505.000,00 € 505.000,00

Inkomst andere financiering of

eigen inkomsten

Inkomst: Reserveoverdracht van

een jaar ervoor

Totaal beschikbaar budget € 505.000,00 € 505.000,00 € 505.000,00 € 505.000,00 € 505.000,00

Kost: Personeel, direct € 407.250,00 € 390.706,75 € 391.243,75 € 391.523,25 € 376.753,72

Kost: Personeel, indirect € - € - € - € - € -

Kost: Werking direct

Informatica en documentatie € 5.550,00 € 5.600,00 € 5.600,00 € 5.600,00 € 5.400,00

ICT € 4.000,00 € - € - € - € -

Uitrusting € 2.650,00 € 3.200,00 € 3.200,00 € 3.200,00 € 3.100,00

Reiskosten € 7.650,00 € 10.200,00 € 10.200,00 € 10.200,00 € 7.750,00

Analysekosten € 52.104,55 € 69.497,80 € 68.960,80 € 68.681,30 € 84.200,83

Valorisatie € - € - € - € - € 2.000,00

Totale kost € 71.954,55 € 88.497,80 € 87.960,80 € 87.681,30 € 102.450,83

Kost: Werking, indirect

Informatica en documentatie

ICT

Uitrusting

Reiskosten

Analysekosten

Valorisatie

Totale kost € - € - € - € - € -

Centrale beheerskosten en

algemene exploitatiekosten € 25.795,45 € 25.795,45 € 25.795,45 € 25.795,45 € 25.795,45

Kost: onderaanneming € - € - € - € - € -

Totale gemaakte kosten € 505.000,00 € 505.000,00 € 505.000,00 € 505.000,00 € 505.000,00

Saldo (over te dragen naar volgend

jaar ) € 0,00 € 0,00 € 0,00 € 0,00 € 0,00

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1. Hänninen, O.; Knol, A. B.; Jantunen, M.; Lim, T.-A.; Conrad, A.; Rappolder, M.; Carrer, P.; Fanetti, A.-C.; Kim, R.; Buekers, J.; Torfs, R.; Iavarone, I.; Classen, T.; Hornberg, C.; Mekel, O. C. L. Environmental burden of disease in Europe: assessing nine risk factors in six countries. Environ. Health Perspect. 2014, 122, 439–46.

2. Angerer, J.; Bird, M. G.; Burke, T. A.; Doerrer, N. G.; Needham, L.; Robison, S. H.; Sheldon, L.; Zenick, H. Strategic biomonitoring initiatives: moving the science forward. Toxicol. Sci. 2006, 93, 3–10.

3. Angerer, J.; Aylward, L. L.; Hays, S. M.; Heinzow, B.; Wilhelm, M. Human biomonitoring assessment values: approaches and data requirements. Int. J. Hyg. Environ. Health 2011, 214, 348–60.

4. Hays, S. M.; Becker, R. A.; Leung, H. W.; Aylward, L. L.; Pyatt, D. W. Biomonitoring equivalents: a screening approach for interpreting biomonitoring results from a public health risk perspective. Regul. Toxicol. Pharmacol. 2007, 47, 96–109.

5. Schoeters, G. E. R.; Den Hond, E.; Koppen, G.; Smolders, R.; Bloemen, K.; De Boever, P.; Govarts, E. Biomonitoring and biomarkers to unravel the risks from prenatal environmental exposures for later health outcomes. Am. J. Clin. Nutr. 2011, 94, 1964S–1969S.

6. Schoeters, G.; Den Hond, E.; Colles, A.; Loots, I.; Morrens, B.; Keune, H.; Bruckers, L.; Nawrot, T.; Sioen, I.; De Coster, S.; Van Larebeke, N.; Nelen, V.; Van de Mieroop, E.; Vrijens, J.; Croes, K.; Goeyens, K.; Baeyens, W. Concept of the Flemish human biomonitoring programme. Int. J. Hyg. Environ. Health 2012, 215, 102–8.

7. Schroijen, C.; Baeyens, W.; Schoeters, G.; Den Hond, E.; Koppen, G.; Bruckers, L.; Nelen, V.; Van De Mieroop, E.; Bilau, M.; Covaci, A.; Keune, H.; Loots, I.; Kleinjans, J.; Dhooge, W.; Van Larebeke, N. Internal exposure to pollutants measured in blood and urine of Flemish adolescents in function of area of residence. Chemosphere 2008, 71, 1317–25.

8. Koppen, G.; Den Hond, E.; Nelen, V.; Van De Mieroop, E.; Bruckers, L.; Bilau, M.; Keune, H.; Van Larebeke, N.; Covaci, A.; Van De Weghe, H.; Schroijen, C.; Desager, K.; Stalpaert, M.; Baeyens, W.; Schoeters, G. Organochlorine and heavy metals in newborns: results from the Flemish Environment and Health Survey (FLEHS 2002-2006). Environ. Int. 2009, 35, 1015–22.

9. Keune, H.; Morrens, B.; Croes, K.; Colles, A.; Koppen, G.; Springael, J.; Loots, I.; Van Campenhout, K.; Chovanova, H.; Schoeters, G.; Nelen, V.; Baeyens, W.; Van Larebeke, N. Opening the research agenda for selection of hot spots for human biomonitoring research in Belgium: a participatory research project. Environ. Health 2010, 9, 33.

10. Knudsen, L.; Merlo, D. F. Biomarkers and Human Biomonitoring Volume 1 : Ongoing Programs and Exposures. In; Thomas Graham House, Science Park, Milton Road, 2012; pp. 135–165.

11. Sioen, I.; Den Hond, E.; Nelen, V.; Van de Mieroop, E.; Croes, K.; Van Larebeke, N.; Nawrot, T. S.; Schoeters, G. Prenatal exposure to environmental contaminants and behavioural problems at age 7-8years. Environ. Int. 2013, 59, 225–31.

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12. Van Larebeke, N.; Sioen, I.; Hond, E. Den; Nelen, V.; Van de Mieroop, E.; Nawrot, T.; Bruckers, L.; Schoeters, G.; Baeyens, W. Internal exposure to organochlorine pollutants and cadmium and self-reported health status: a prospective study. Int. J. Hyg. Environ. Health 2015, 218, 232–45.

13. Morrens, B.; Bruckers, L.; Hond, E. Den; Nelen, V.; Schoeters, G.; Baeyens, W.; Van Larebeke, N.; Keune, H.; Bilau, M.; Loots, I. Social distribution of internal exposure to environmental pollution in Flemish adolescents. Int. J. Hyg. Environ. Health 2012, 215, 474–81.

14. Croes, K.; Den Hond, E.; Bruckers, L.; Loots, I.; Morrens, B.; Nelen, V.; Colles, A.; Schoeters, G.; Sioen, I.; Covaci, A.; Vandermarken, T.; Van Larebeke, N.; Baeyens, W. Monitoring chlorinated persistent organic pollutants in adolescents in Flanders (Belgium): concentrations, trends and dose-effect relationships (FLEHS II). Environ. Int. 2014, 71, 20–8.

15. Parent, A.-S.; Franssen, D.; Fudvoye, J.; Gérard, A.; Bourguignon, J.-P. Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents. Front. Neuroendocrinol. 2015, 38, 12–36.

16. 3xG http://www.studie3xg.be/.

17. ENVIRONAGE https://erc.europa.eu/unravelling-environmental-exposures-core-axis-ageing.

18. IPANEMA https://clinicaltrials.gov/ct2/show/NCT02592005.

19. IPANEMA http://www.uza.be/luchtvervuiling.

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