Human biomonitoring: Science and policy for a healthy future, April 17–19, 2016, Berlin, Germany

Accepted Manuscript Title: Human biomonitoring: Science and policy for a healthy future, April 17–19, 2016, Berlin, Germany Author: Anke Joas PII: DOI: Reference:

S1438-4639(17)30058-5 http://dx.doi.org/doi:10.1016/j.ijheh.2017.01.013 IJHEH 13044

To appear in: Author: Gerda Schwedler PII: DOI: Reference:

S1438-4639(17)30058-5 http://dx.doi.org/doi:10.1016/j.ijheh.2017.01.013 IJHEH 13044

To appear in: Author: Judy Choi PII: DOI: Reference:

S1438-4639(17)30058-5 http://dx.doi.org/doi:10.1016/j.ijheh.2017.01.013 IJHEH 13044

To appear in: Author: Marike Kolossa-Gehring PII: DOI: Reference:

S1438-4639(17)30058-5 http://dx.doi.org/doi:10.1016/j.ijheh.2017.01.013 IJHEH 13044

To appear in: Please cite this article as: Kolossa-Gehring, Marike, Human biomonitoring: Science and policy for a healthy future, April 17–19, 2016, Berlin, Germany.International Journal of Hygiene and Environmental Health http://dx.doi.org/10.1016/j.ijheh.2017.01.013

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Meeting Report Human biomonitoring: Science and policy for a healthy future. April 17 – 19, 2016, Berlin, Germany Authors: Anke Joas (corresponding author) Consultancy for Integrated Solutions/BiPRO, Munich, Germany Gerda Schwedler, German Environment Agency/UBA, Dessau-Roßlau/Berlin, Germany Judy Choi Consultancy for Integrated Solutions/BiPRO, Munich, Germany Marike Kolossa-Gehring German Environment Agency/UBA, Dessau-Roßlau/Berlin, Germany

Summary Following the success of the 1st International Conference on Human Biomonitoring (HBM) in Berlin in 2010, the 2nd International Conference on Human Biomonitoring took place in Berlin from April 17-19, 2016 for an exchange and updates among participants on all aspects relating to HBM. Entitled “Science and Policy for a Healthy Future”, the conference brought together international experts from the scientific sector, politics, authorities, industry, non-governmental organizations (NGOs), and other involved associations. The conference took a critical look at today’s chemicals that have a potential impact on human health and should be investigated as a matter of priority. It also discussed current activities and research efforts on HBM occurring worldwide, presented HBM success stories, and emphasized areas, where further research and focus are needed to improve the use of HBM for policy making. In many countries, HBM has been proven to be a useful tool and warning system to indicate problematic human exposure to pollutants and to evaluate the effectiveness of existing chemicals policy and regulations. However, important challenges remain such as exposure assessment of mixtures of chemicals, the development of analytical methods to detect new chemicals of concern (e.g., substitutes for phthalates), the identification of exposure sources, and the assessment of the impact of exposure on health. This brief report summarizes the discussions and contributions from this conference, which was jointly organized by the German Federal Environment Agency (UBA) and the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMUB). Background The environment has a significant impact on human health. According to new estimates of the WHO, 12.6 million people died as a result of living or working in an unhealthy environment in 2012 – nearly 1 in 4 of global deaths (Prüss-Ustün et al., 2016). Strategies and policy actions for improving the environment can therefore help reduce the adverse health effects. For example, the 1

implementation of smoking bans in public environments leading to reduced exposure to secondhand smoke improves health outcomes of workers and the general population (CDC, 2014). Environmental chemicals and contaminants are ubiquitous and can be found in water, air, soil as well as in industrial products, consumer goods, and food products. As humans are substantially exposed to these chemicals in their everyday lives, it is important to monitor their exposure to such chemicals, to identify contamination sources, and to assess the chemicals’ impacts on health. An important tool for detecting environmental chemicals in the human body is HBM. HBM measures chemicals in body tissues and fluids using biological specimens such as blood, urine, and hair. HBM considers all routes of uptake and all relevant sources, and by linking biomonitoring results with environmental and health data, HBM can also connect exposure to pollutants to health effects. HBM is thus an ideal instrument for risk assessment and risk management for both scientists and policy makers by detecting human exposure to chemicals, recognizing deficits in protection of the public against critical substances, and measuring the success of chemicals regulation (Angerer et al., 2006). Reduced exposures to chemicals of concern are observed after bans of chemicals and risk reduction measures (Becker et al., 2013; Kolossa et al., 2012). However, restricted chemicals can be substituted by substances, for which no assessment of their health relevance is available. With appropriate analytical methods, HBM can also support scientists and policy makers to assess currently-used as well as emerging chemicals that have the potential to harm human health and thus should be investigated and regulated as a matter of priority. HBM in policy making: Still a work in progress The conference began with a discussion featuring panelists coming from academia, government, industry, NGOs and international organizations (e.g., the WHO) discussing the applicability of HBM in policy making. It was generally agreed among all the panelists that HBM can be a very useful tool in determining internal exposure in humans and, combined with toxicological assessments, provide a strong basis for sound risk assessment and regulatory measures. However, there remain challenges that need to be overcome before HBM can be more effectively used in policy making. The panelists agreed that time is a major driving force when it comes to policy actions. Policy makers are often required to produce quick responses when problems arise and therefore need timely access to reliable HBM data in order to come up with sound policy actions. The general population, especially vulnerable groups such as pregnant women or children, deserves to know what chemicals they are exposed to in the environment. Therefore, policy makers need to ensure that the right message is delivered at the right time while concurrently preventing unnecessary fear in the public. The panelists also agreed that, ideally, information on exposure levels should be accompanied by information on the health relevance of such exposures. As it was conveyed that “HBM makes pollution personal”, communication of HBM results to the public might enable the public to take their own personal actions in order to reduce their exposure to potentially harmful chemicals. Simply measuring the levels of chemicals in humans is not sufficient to regulate chemicals as not all chemicals cause adverse health effects. Toxicological assessments are also required to identify the potential hazards of chemicals and to justify regulatory actions. The speakers highlighted that 2

this is a challenging task to accomplish as it often requires different approaches and a long time to collect sufficient hazard data of a chemical. There are currently 15 bodies of EU legislation (e.g. REACH), where HBM can have an impact. At the same time, one-third of the countries in the geographical Europe do not have regulations regarding chemical exposure. The panelists agreed that more cooperation, networking, and joint programs can assist these countries to promote HBM as a tool of chemicals regulation. The conclusion of the first panel discussion was followed by the scientific program. The content of the different sessions is outlined below. New developments in national HBM programs Since their inception, a number of well-established large-scale national HBM programs such as United States’ (US) National Health and Nutrition Examination Survey (NHANES), Canadian Health Measures Study (CHMS) and German Environmental Survey (GerES) have continued their efforts to conduct HBM to monitor the chemical exposure of their respective populations. Emerging chemicals such as alternative chemicals to phthalates (e.g., DINCH) have been included into the chemical analysis of these national HBM programs, and some of these programs have also shifted their focus towards vulnerable populations such as children and pregnant women. The NHANES program has been conducted annually by the US Centers for Disease Control and Prevention since 1999 (Calafat, 2012). Not only does NHANES collect data on the health and nutritional status of the general American population, but it also collects biological specimens in order to observe exposure to a number of selected environmental chemicals within the population. Recent advances in the NHANES program have been the inclusion and analysis of chemicals found in consumer products (namely a phthalate substitute DINCH and insect repellent DEET), the introduction of pooling biological samples to improve detection and decrease analytical cost, and the expansion of participants to specifically collect urine samples from pre-school aged children. NHANES data has been proven useful in providing exposure information for risk assessment, particularly in the evaluation of effectiveness of public health measures. Case in point, the exposure trends of various phthalates in the general American population are changing due to legislative actions taken on some phthalates (e.g., DEHP) as well as the increased use of phthalate substitutes such as DiNP and DINCH (Calafat, 2016). As a component of the Chemicals Management Plan, the CHMS is an ongoing cross-sectional direct measures survey implemented in 2-year cycle in Canada. The objectives of CHMS regarding HBM is to determine nationally-representative concentrations of environmental chemicals in biological specimens (blood, urine, and hair) and provide biomonitoring data to elucidate temporal trends of chemical exposure, to facilitate data comparison among sub-populations in Canada and other countries, and to identify any potential exposure sources (e.g., smoking leading to increased blood levels of benzene, toluene, ethylbenzene, and xylenes, collectively known as BTEX) (Haines and Murray, 2012). Currently, CHMS biomonitoring data have been used to achieve the following: (1) establish baseline concentrations of chemicals in the general Canadian population, (2) inform chemical risk assessment and risk assessment activities, (3) assess effectiveness of regulatory and risk management actions, and (4) fulfill national and international reporting requirements. HBM data for CHMS cycles 1 to 3 (i.e. from 2007-2013) are published and available online, and HBM data for cycle 4 is expected to be available in July 2017 (Haines, 2016). 3

The German Environment Agency (UBA) employs two major HBM studies: (1) the German Environmental Survey (GerES), a cross-sectional and population-representative study, and (2) the Environmental Specimen Bank (ESB), a monitoring tool for time trends analyses of pollutants in humans and in the environment (Kolossa-Gehring et al., 2012). HBM data generated from these programs can be used to evaluate potential health risks, e.g., by comparing the data with HBM-based guidance values such as HBM-I and HBM-II values as derived by the German HBM Commission (Apel et al., 2016). Similar to the observations made from the NHANES program, the levels of certain phthalates such as DEHP and DnBP have also decreased over time due to enforced regulations to restrict the use of certain phthalates, whereas levels of alternative phthalate substitutes such as DiNP have steadily risen over time due to its increased production and use. Continued HBM efforts from UBA include leading the Europe-wide consortium (HBM4EU) in the establishment of a harmonized and sustainable HBM program in Europe as well as collaborating with the BMUB and the German Chemical Association (VCI) in the development of new analytical HBM measures for substances that might be relevant when it comes to exposure for the general public or health effects (KolossaGehring, 2016). In France, a national biomonitoring program has been established in order to estimate the exposure of the general French population to various chemicals and to better understand the determinants of chemical exposures (Fréry et al., 2012). There are two main studies within this national biomonitoring program: (1) the ESTEBAN cross-sectional survey, featuring the French continental population aged 6-74, and (2) the ELFE longitudinal cohort survey, featuring pregnant women and their newborns. In order to determine the key chemicals and biomarkers to be analyzed in both studies, a working group consisting of members of the various French ministries (e.g., health, ecology, and labor) and public health agencies was established. The working group employed the Delphi method to obtain a consensus prioritization list of over 100 biomarkers to be included in the French national biomonitoring program. Outcomes of the analyses of these substances from the ELFE and ESTEBAN studies are expected in 2017 (Fillol, 2016). In addition from the well-established national HBM programs, there are other efforts worldwide to initiate cross-sectional HBM surveys in smaller countries. For example, there has been significant progress in the use of HBM as a tool for environmental health policy and research in Israel (Berman et al., 2012). Results from the 2011 Ministry of Health biomonitoring study showed widespread exposure to environmental tobacco smoke and high levels of organophosphate pesticide metabolites in the Israeli general adult population, and such findings were used to support policies to expand smoking ban in public places and to phase out or reduce the use of several agricultural pesticides, respectively. Current developments include (1) the establishment of the National Health and Nutrition Survey (MABAT) with the goal of combining HBM data on exposure to pesticides and environmental tobacco smoke with data on diet, health behavior, and health outcomes and (2) emerging HBM birth cohort and research studies, e.g., to study adverse health effects of phthalates, brominated frame retardants, and organophosphate pesticides or to investigate human exposure to pharmaceuticals from treated wastewater. Future goals for Israel are to develop a national HBM laboratory, to consolidate a long term national HBM plan, and to participate in the regional HBM program in order to improve data harmonization (Berman, 2016). Since the implementation of the South Korean Environmental Health Act in 2009, there is a legal obligation to conduct HBM studies in South Korea in order to determine the levels of exposure to harmful environmental chemicals and exposure pathways in the general Korean population. This 4

consequently led to the establishment of the Korean National Environmental Health Survey (KoNEHS), a nationwide population study carried out in 3-year cycles and currently running its 3rd cycle. For the 3rd cycle, KoNEHS expanded the target population to include children and adolescents and included analyses of chemicals of recent public interest or concern such as substitutes of bisphenol A and parabens due to increased use of hand disinfectants. The results of the KoNEHS are announced as National Statistics, and the raw data are available to the researchers and public (Kim, 2016). Although the size, study design and selection of chemicals of these national HBM programs might vary, they all have a similar goal: to provide scientifically-sound evidence for policy making. HBM in large scale birth cohorts The recognition of the special vulnerability of the child to environmental hazards has resulted in the establishment of longitudinal birth cohorts in a number of countries such as Canada, Japan, China (primarily in Shanghai), France, Denmark, and Norway in order to determine the relationships between environmental exposures and child health outcomes. The ultimate goal of these HBM cohort studies is to achieve primordial prevention of disease such that conditions can be established and maintained to minimize hazards to health (Etzel, 2016). The Canadian MIREC study is a national-level pregnancy cohort study with the objectives to obtain on maternal and newborn exposure to priority environmental chemicals in Canada and to investigate potential associations between early life exposure to environmental chemicals and adverse health effects of pregnant women and their newborns. Over 2,000 pregnant women were recruited all across Canada for the MIREC study and provided biological samples (e.g. maternal blood, urine, DNA, milk, etc.) for the analyses of chemicals such as phthalates, bisphenol A, pesticides, metals, and POPs among others. In addition to pregnant women, MIREC intends to include the newborns and perform follow-up analyses potentially up to adolescence. Results from this study can be compared to the results from the cross-sectional population survey CHMS as well as from surveys or programs from other countries. A biobank has also been established from the MIREC study, enabling ancillary research studies (e.g., impact of prenatal exposure to chemicals on immune system development in newborns) to take place (Fraser, 2016). In 2011, the Japanese Ministry of the Environment initiated the Japan Environment and Children’s Study (JECS) with the objective to evaluate the effect of the environment on children’s health and development. Since its inception, JECS completed its three-year recruitment of 103,103 pregnant women and collected over 5 million aliquots of biological samples for analysis. JECS is currently developing high throughput analytical methods to automate and process the large number of samples at low cost and planning to analyze levels of heavy metals, per- and polyfluoroalkyl substances (PFASs), phthalate metabolites, parabens, nicotine metabolites, and oxidative stress biomarkers. JECS intends to do routine follow-ups of the participants until the children reach 13 years of age (Nakayama, 2016). The objective of the Shanghai Birth Cohort in China is to study the effects of genetic, environmental, and behavioral factors on reproductive health, pregnancy outcomes, child growth and development, and disease risks. A total of 1,183 couples who planned to conceive in Shanghai were recruited between 2013 and 2015 for the study, and biological samples were collected for analyses of chemicals. Follow-up visits are expected until the children reach 24 months of age. Within 5

this cohort, a smaller nested case-control study consisting of infertile women as cases and fertile women as controls demonstrated that infertile women had higher levels of triclosan and certain pesticides in their body than control fertile women. Additional studies are currently underway to further investigate the association between exposure to triclosan and adverse reproductive health effects (Zhang, 2016). The ELFE birth cohort is a part of the French national biomonitoring program with the objectives to determine the extent of chemical exposure in French pregnant women and to identify the determinants of exposure when possible. A total of 4,145 pregnant women were randomly selected in 2011 as participants to provide a representative population of mothers having given birth in continental France, and biomarkers of exposure for metals, bisphenol A, phthalates, and some pesticides were measured in biological samples collected from these participants. The outcome of this study provided the first overview of the extent of chemical exposure in French mothers giving birth. Future plans of the ELFE cohort include the development of reference values for this vulnerable French population and further studies to possibly link maternal exposure to chemicals and adverse health effects or development in children (Denys, 2016). Even the largest of the birth cohorts, however, are not big enough to study rare childhood diseases and outcomes. To increase the sample size, efforts are made to pool data. A major challenge of birth cohort studies, however, is the difficulty of comparing results among studies. Therefore, since 2011, the Environmental and Child Health International Birth Cohort Group, composed of study teams from Japan, France, China, and Germany, has been convening to exchange information and to work towards harmonization of processes that would provide the opportunity to compare methods and develop procedures to conduct combined analyses of results and data pooling procedures. Such efforts can relieve huge burden with planning and execution of study design, potentially enable investigation of rare childhood outcomes, and enhance the attention of policymakers to understanding children’s exposures (Etzel, 2016). Broadening the HBM toolbox The identification of chemicals with potential consumer exposure and health relevance for the population and the development of sensitive analytical methods to measure the exposure are continuous tasks in HBM. Therefore, the fundamental objective of the collaboration between BMUB and VCI and UBA as key partner is the development of biomonitoring methods for selected substances, for which no suitable analytical method exists. Novel specific and sensitive biomonitoring methods for emerging chemicals, such as di(2-propylheptyl)phthalate (DPHP), 2mercaptobenzothiazole (MBT), 4-nonylphenol, and hexabromocyclododecane (HBCDD), have been developed. Some of these methods have been already employed in the GerES and ESB, e.g., for DPHP and MBT. HBM-values for these substances have also been derived by the German HBM Commission to evaluate the population exposure (Leng, 2016). The quality of HBM studies heavily relies on the well-considered choice of the biomarker as well as the matrix. For non-persistent chemicals, which are excreted quickly, urine is the compartment with the highest concentrations of the biomarker or its metabolites. The nonpersistent nature of many novel chemicals also creates new challenges in interpreting the extent and duration of exposures. Special sample collection strategies in conjunction with an appropriate set of biomarkers can strengthen the significance of HBM data (Koch, 2016). 6

It was emphasized throughout the conference that to measure a single chemical in human biological samples is not optimal in HBM studies as there is limited amount of sample, time, and finance to only evaluate single substances. Therefore, there is a need for high-throughput technology such as the use of –omics techniques and exposomes in HBM. The concept of the “exposome” was first proposed in 2005 (Wild, 2005), which refers to the totality of environmental exposures from conception onwards and over a complete lifetime. The exposome is based on measurements using high-throughput –omics techniques in biological samples of complete sets of biomarkers of exposure ranging from xenobiotics and their metabolites in blood (metabolomics) to covalent complexes with DNA and proteins (adductomics). Examples of study and interpretation approaches were presented and discussed (Vineis, 2016). HBM in health risk assessment HBM data alone cannot provide information on health risks of exposure to chemicals. In order to understand the potential relationships between body burden of chemicals and adverse health effects, toxicological assessments are needed. Taking this in consideration, the German HBM Commission and experts from North America have continued to develop health related guidance values, namely HBM-values and biomonitoring equivalents (BEs), respectively, that allows interpretation of HBM outcomes in a public health context. Significant progress has been made in the recent years in the development of these guidance values, which consequently has led to increased application and interpretation of HBM data for risk assessment. The German HBM Commission is an interdisciplinary task force affiliated to the German Environment Agency, comprising experts of various scientific fields. The objective of the HBM Commission is to harmonize the activities and assessments in the field of HBM within Germany, mainly to evaluate the HBM concepts and to derive HBM values (Schulz et al., 2007). To do this, the group meets twice a year to discuss current chemicals/issues of concern, evaluate scientific data and derive HBM values based on available toxicological and/or epidemiological data. As mentioned earlier, two types of HBM values have been derived by the German HBM Commission: HBM-I and HBM-II values. HBM-I value represents the concentration of a substance, below which there is no risk for adverse health effects, whereas HBM-II value represents the concentration, above which there is an increased risk for adverse health effects, and should be considered as an action or prevention level that measures to reduce exposure are needed. HBM-values that have been derived for different contaminants such as metals, phthalates and polychlorinated biphenyls (PCBs) can be found online on the UBA’s homepage: https://www.umweltbundesamt.de/en/image/current-humanbiomonitoring-hbm-values-for-blood (Kraft, 2016). Since 2008, experts from Health Canada have been developing BE values to screen and evaluate biomonitoring measures from the general Canadian population by different strategies of pharmacokinetic modeling and data. Efforts were made to expand into guidance values which led to the increased application of scientific biological data with BEs as a valuable exposure and biomonitoring screening tool for health risk assessment of environmental contaminants in Canada (Nong, 2016). The Canadian government also currently uses HBM data as part of the regulatory risk assessment under their Chemicals Management Program (CMP). Since its launch in 2006, the CMP identified approximately 4,300 substances with potential health and ecological risks that require further attention and assessments. Ten years later, about 3,000 substances have assessed by the Canadian government, and some of these assessments (e.g., for bisphenol A, lead, triclosan, 7

phthalates, etc.) have used quantitative HBM data to draw conclusions about potential risk to human health. These examples highlight the impact and overall role HBM has had in regulatory decision making as well as criteria used in the application of HBM data in human health risk assessment (Zidek, 2016). As humans are exposed not just to a single but rather a plethora of substances, the challenge of how to assess levels of chemical mixtures was brought into discussion. At the National Institute of Environmental Health Sciences in the United States, research efforts on mixtures have been made. One example brought into discussion was the effects of anti-androgenic chemical mixtures (mainly phthalates as reproductive toxicants) on reproductive tract development in rats. Observed mixture data were compared to mathematical mixture model predictions to determine how the individual chemicals in a mixture interact, and for a mixture of phthalates, there is an observed dose-additive effect based on the relative potency of the individual phthalates to suppress fetal testosterone production (Howdeshell, 2016). Such results underline that efforts must be taken to further investigate the joint action of chemical mixtures and urgently work on the development of cumulative risk assessment. Harmonizing HBM approaches and data – progress in the international and European landscape In this scientific session, experiences and lessons learned from already realized harmonization projects were presented and discussed; an outlook was also given on emerging European and international initiatives. There is increasing scientific evidence that endocrine disrupting chemicals (EDCs) contribute substantially to disease and disability. In order to estimate health costs due to EDCs, the consensus strategy was presented to a steering committee of endocrine disruptor experts to achieve consensus for probable EDC causation for intellectual disability, autism, obesity, diabetes, and male infertility among others. Further topics of current environmental burden of disease harmonization approaches should comprise embracing probability of causation, accepting subclinical effects and coordinated biomonitoring programs (Trasande, 2016). Although NHANES has generated extensive amount of biomonitoring data of the exposure to environmental chemicals of the general American population, there is a need of biomonitoring data on US state level, especially where exposure to environmental contaminants is a concern and public health responses to chemical exposure emergencies are needed. Therefore, the Association of Public Health Laboratories (APHL), with support from the broader environmental health community, established a National Biomonitoring Network (NBN) for consistent and high-quality biomonitoring measurements on regional level. Through this network, guidance documents and online tools assist state laboratories and scientists with starting a biomonitoring program. The NBN will strive to incorporate biomonitoring measurements into routine public health surveillance. This will facilitate data comparison across multiple levels and public health practitioners to better address communityspecific exposure and needs (Latshaw, 2016). In order to establish a European-wide HBM-network, scientists and stakeholders from 35 institutions in 27 European countries came together to form the Consortium to Perform Human Biomonitoring on a European Scale (COPHES). Funded by the EU under the Seventh Framework Program, COPHES’ aim was to develop a coherent and harmonized approach to HBM in Europe by means of commonly developed protocols, strategies, and scientific tools to ensure reliable and comparable data. To test the feasibility of such approach in Europe, a twin project, titled 8

Demonstration of a Study to Coordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES), ran from September 2010 to November 2012. The outcomes of the COPHES/DEMOCOPHES are published in various scientific journals and also posted in the project website (http://www.eu-hbm.info). With COPHES/DEMOCOPHES, the first steps to assess personal chemical exposures in Europe as a whole was taken. Key success factors were the harmonized protocol development, intensive training and capacity building for field work, chemical analysis, results communication, and stringent quality control programs for chemicals and data analysis (Den Hond et al., 2015) Experiences were gained as well to improve data management and to address legal and financial needs of a sustainable EU-wide HBM program. In summary, the feasibility of a Europe-wide human biomonitoring framework was demonstrated (Joas, 2016; Schoeters, 2016). These experiences gained from COPHES/DEMOCOPHES served as the basis for a number of EU-funded health-related projects such as BRIDGE Health (http://www.bridge-health.eu/) as well as the basis for the European Joint Program on HBM, entitled HBM4EU. Led by the German Environment Agency and bringing together experts from 26 participating countries as well as from the European Environment Agency, HBM4EU is a response to a call launched by the European Commission under the Horizon 2020 Framework Program. The long-term objective of HBM4EU is the establishment of a sustainable HBM program within Europe, including continued harmonization in HBM procedures across Europe, data collection and collation via a centralized data portal (Information Platform for Chemical Monitoring , IPChem), and generating scientific evidence on causal links among chemical exposure, external exposure, and adverse health effects. Knowledge gained from this program will be directly provided to policy makers in the EU, enabling them to evaluate if current policy needs can be addressed with existing data and to potentially set new priorities to protect citizens Europe-wide. More information about HBM4EU can be found in this website: https://ec.europa.eu/research/conferences/2016/hbm4eu/index.cfm. The tasks ahead for HBM Upon completion of the scientific program, a second and final panel discussion was set to identify and discuss further need for action in HBM. The panel discussion consisted of representatives from WHO, the European Environment Agency, the BMUB, the VCI, and the Public Health Services Gelderland-Midden. The question raised in this panel discussion was “What do we want to see HBM in 5-6 years?” From the side of the international and European agencies, it was conveyed that, although HBM is an important tool, it is also currently lacking in environmental health policies. For example, HBM has contributed to the success of reducing exposure of some key chemicals such as lead. HBM data indicated that blood lead levels were reduced in the general population as a result of the ban of using lead in fuel. However, HBM appears to be insufficient to facilitate the phase-out of lead in paint. Even though there are plans to phase out lead in paint by 2020, only 53 countries worldwide, which 50% among them are European countries, have been complying with the plans. Therefore, the panelists agreed that global alliance and continuous support by HBM measurements are needed, e.g., for enforcing lead legislations worldwide. As promising and future steps to facilitate the use of HBM in international environmental health policies, further projects were presented in the discussion. First, the WHO has initiated and supported the establishment of the Chemical Risk Assessment Network, which collects and provides 9

chemical data in a single data portal for easy-to-access use. The panelists agreed tools and methods like the Chemical Risk Assessment Network to provide quick and easy access to HBM data would facilitate sound policy decision making. Second, in the European Union Framework Program for Research and Innovation (Horizon 2020), the European Human Biomonitoring Initiative HBM4EU was established and is working towards implementing a Europe-wide sustainable HBM program. Moreover, HBM4EU intends to establish a dialogue among all involved stakeholders and to bridge science, risk assessment, and risk management in environmental health policy. The panelist from VCI stated that due to the potential occupational hazards of the workers and general public concerns about the chemicals used in the market, the chemical industry sector has also gained experience (tools and knowledge) in HBM and strives to produce sustainable products with minimal risks to their consumers. Particularly in Germany, the collaboration between the government (BMUB) and the industry (VCI) to develop and validate analytical methods for the detection of chemicals has been successful so far. Analytical methods for 50 chemicals have been developed in this collaboration, which is continuing to run smoothly. It was discussed whether it is an option in the future to extend this collaboration beyond Germany, e.g., to encourage more collaborations outside Germany among producers, manufacturers, and the governments. The sentiment of having more and closer collaborations was also expressed by the Public Health Services Gelderland-Midden. Regardless of the level (i.e., global, European, national, or regional), all panelists highlighted that one of the future goals for HBM is to further expand collaborations and harmonize HBM. Collaborations should not only occur among countries, institutions, and researchers but also include other stakeholders such as NGOs, local community/citizens, and medical doctors. Conclusion Over time, significant progress and new developments in HBM have been made. Longstanding HBM programs are changing their focus to include analysis of emerging chemicals and susceptible populations, and more reference values have been developed. Also, new national programs are being established and are well underway. There are not only large-scale national population survey programs but also large-scale birth cohorts with intention to conduct follow-ups of newborns until they reach childhood. Focused research efforts have been made to investigate the detection and effects of chemicals in mixtures as well as novel chemicals used as alternatives to banned substances. HBM data alone cannot solely be used in policy making as health impacts and toxicological effects of chemicals are required for sound risk assessment. The German HBM Commission derives HBM values to help with the interpretation of HBM results in regards to potential health impacts. In Canada and the USA, new BE values have also been derived for the interpretation of HBM data. However, there remain gaps in the applicability of HBM in policy making, and there are still complex challenges ahead. To further strengthen the effective use of HBM, the following current concerns should be considered and reflected:   

Better understanding between both the scientists and the policy makers HBM harmonization among countries, while improved, remains a constant topic HBM needs to go beyond analyzing single substances and proceed to mixture analysis. 10

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Constant identification of new chemicals and development of analytical methods (via non-target screening as well)

UBA and BMUB aim to organize more HBM conferences in the future to continue promoting and strengthening network and cooperation between all stakeholders in order to further promote the use of HBM to shape a healthy future.

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References Berman, T., 2016. Human Biomonitoring in Israel - recent results and development, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Calafat, A., 2016. Biomonitoring in NHANES - Recent advances and future directions, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. CDC, 2014. Smokefree Policies Improve Health. Available from: http://www.cdc.gov/tobacco/data_statistics/fact_sheets/secondhand_smoke/protection/improve_h ealth/. Denys, S., 2016. HBM in the ELFE birth cohort - results to date, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Etzel, R., 2016. Pediatric environmental health - the role of biomonitoring in birth cohorts, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Fillol, C., 2016. National human biomonitoring programme in France: selection of substances and prioritization of biomarkers, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Fraser, W., 2016. Maternal-Infant Research on Environmental Chemicals (MIREC) - a Canadian biomonitoring birth cohort research platform, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Haines, D., 2016. Human Biomonitoring in the Canadian Health Measures Survey - Progress and Uses, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Howdeshell, K., 2016. Mixed exposure evaluation of pesticides and toxic substances, cumulative risk assessment, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Joas, A., 2016. Lessons learned from the COPHES/DEMOCOPHES process, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Kim, S., 2016. Introduction of Korean National Environmental Health Survey (KoNEHS), 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Koch, K.M., 2016. The quest for biomarkers of exposure to non-persistent chemicals, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Kolossa-Gehring, M., 2016. The German Environmental Survey and the Environmental Specimen Bank - HBM for policy decisions, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Kraft, M., 2016. HBM-values derived by the German HBM Commission and their practical use, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Latshaw, M.W., 2016. USA's National Biomonitoring Network, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Leng, G., 2016. New specific and sensitive biomonitoring methods for chemicals of emerging health relevance, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Nakayama, S., 2016. Japan's Environment and Children Study - lessons learned from incorporating HBM in a large-scale birth cohort study, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Nong, A., 2016. Pharmacokinetic modeling of health and exposure measures to support health risk interpretations, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. 12

Prüss-Ustün, A., Wolf, J., Corvalán, C., Bos, R., Neira, M., 2016. Preventing disease through healthy environments: a global assessment of the burden of disease from environmental risks, in: WHO (Ed.). Schoeters, G., 2016. Results of the first Europe-wide HBM study, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Trasande, L., 2016. Harmonizing burden of disease estimation due to environmental chemicals, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Vineis, P., 2016. The role of the "omics-techniques" in HBM, current and future applications, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Zhang, J.J., 2016. The Shanghai Birth Cohort - current status and results, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany. Zidek, A., 2016. HBM data used in regulatory risk assessment under Canada's chemicals management program, 2nd International Conference on Human Biomonitoring: Science and policy for a healthy future, Berlin, Germany.

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