Concept FLESH IV

Concept of the research program (FLEHS IV, 2016-2020)

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.

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. 

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 [1] and evidence is growing that puberty is a vulnerable period for health later in life [2]. Alternatively the research consortium has access to birth cohort and samples that have been recently collected (3xG [3], ENVIRONAGE [4], IPANEMA [5,6]). 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 [7]. 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 [8], poorer cognitive or motoric capacities [9] and inflammatory changes [10,11] 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 

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. 

References on this page

1. 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.

2. 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.

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

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

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

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

7. 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.

8. Govarts, E.; Nieuwenhuijsen, M.; Schoeters, G.; Ballester, F.; Bloemen, K.; de Boer, M.; Chevrier, C.; Eggesbø, M.; Guxens, M.; Krämer, U.; Legler, J.; Martínez, D.; Palkovicova, L.; Patelarou, E.; Ranft, U.; Rautio, A.; Petersen, M. S.; Slama, R.; Stigum, H.; Toft, G.; Trnovec, T.; Vandentorren, S.; Weihe, P.; Kuperus, N. W.; Wilhelm, M.; Wittsiepe, J.; Bonde, J. P. Birth weight and prenatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE): a meta-analysis within 12 European Birth Cohorts. Environ. Health Perspect. 2012, 120, 162–70.

9. Kicinski, M.; Vrijens, J.; Vermier, G.; Hond, E. Den; Schoeters, G.; Nelen, V.; Bruckers, L.; Sioen, I.; Baeyens, W.; Van Larebeke, N.; Viaene, M. K.; Nawrot, T. S. Neurobehavioral function and low-level metal exposure in adolescents. Int. J. Hyg. Environ. Health 2015, 218, 139–46.

10. Van Den Heuvel, R. L.; Koppen, G.; Staessen, J. A.; Hond, E. Den; Verheyen, G.; Nawrot, T. S.; Roels, H. A.; Vlietinck, R.; Schoeters, G. E. R. Immunologic biomarkers in relation to exposure markers of PCBs and dioxins in Flemish adolescents (Belgium). Environ. Health Perspect. 2002, 110, 595–600.

11. Gascon, M.; Sunyer, J.; Casas, M.; Martínez, D.; Ballester, F.; Basterrechea, M.; Bonde, J. P.; Chatzi, L.; Chevrier, C.; Eggesbø, M.; Esplugues, A.; Govarts, E.; Hannu, K.; Ibarluzea, J.; Kasper-Sonnenberg, M.; Klümper, C.; Koppen, G.; Nieuwenhuijsen, M. J.; Palkovicova, L.; Pelé, F.; Polder, A.; Schoeters, G.; Torrent, M.; Trnovec, T.; Vassilaki, M.; Vrijheid, M. Prenatal exposure to DDE and PCB 153 and respiratory health in early childhood: a meta-analysis. Epidemiology 2014, 25, 544–53.

For more detailed information you can download the full research progamme.