New HBM values for emerging substances, inventory of reference and HBM values in force, and working principles of the German Human Biomonitoring Commission

AbstractThe German Human Biomonitoring Commission (HBM Commission) derives health-related guidance values (Human Biomonitoring assessment values, HBM values) according to the procedures described in the HBM Commission’s position papers. Since the last adaption of the methodology in 2014, the HBM Commission has established a series of new HBM values, mainly on the basis of internationally agreed TDI/RfD values, or of toxicologically well- founded points of departure observed in animal studies. The derivation of these new HBM values for HBCDD, triclosan, 2-MBT, PFOA and PFOS as well as for the metabolites of glycol ethers, of Hexamoll® DINCH®, DPHP, DEHTP, NMP, NEP, and 4-MBC is specified, and the HBM values are presented together with already established HBM values for other substances. Furthermore, the HBM Commission has defined provisional reference values for 2-methoxyacetic acid and for several parabens in the urine of the German population. It has also updated provisional reference values for PCB in the blood of the German population. An overview of all available reference values is given

Special issue editorial: Key results of the european human biomonitoring initiative - HBM4EU

S

A Phased Approach for preparation and organization of human biomonitoring studies.

Human biomonitoring (HBM) studies like other epidemiological studies are costly and time-consuming. They require the administration of questionnaires and collection of biological samples, putting substantial burden on the participants which may result in low participation rates. The growing importance of HBM studies in epidemiology, exposure assessment and risk assessment underline the importance of optimizing study planning, designing and implementation thus minimizing the above-mentioned difficulties. Based on frameworks from survey design and fieldwork preparation of the European Joint Program HBM4EU, the German Environment Surveys and the COPHES/DEMOCOPHES twin projects combined with elements of project management strategies, a Phased Approach has been developed, introducing a step-by-step guideline for the development of epidemiological studies. The Phased Approach splits the process of developing a study into six phases: Phase 0 (Scoping and Planning): All aspects that are necessary to conduct a study are compiled and put on the agenda for decision-making. Phase 1 (Preparation and Testing): Instruments (e.g. questionnaires), materials (e.g. guidelines, information), and ethics and data management issues, needing thorough preparation and testing before a study can start. Phase 2 (Initiation): Organization and acquisition of necessary equipment and engaging and training personnel. Phase 3 (Implementation): All procedures that require temporal proximity to the start date of fieldwork, such as obtaining contact information of invitees. Phase 4 (Fieldwork and Analysis): Involvement of participants and chemical analysis of the collected samples. Phase 5 (Results and Evaluation): Final procedures leading to closure of the project, such as providing and communicating results. The separation of the planning and conduct of human biomonitoring studies into different phases creates the basis for a structured procedure and facilitates a step-by-step approach reducing costs, warranting high participation rates and increasing quality of conduct. Emphasis is put on a comprehensive scoping phase ensuring high quality of the study design, which is indispensable for reliable results.This document has been created for the HBM4EU project. HBM4EU has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032.S

What is required to combine human biomonitoring and health surveys?

© 2022 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Obtaining holistic information about health and health determinants at the population level should also include data on environmental risk factors of health. So far, only a few countries have combined, at the national level, health and human biomonitoring (HBM) surveys to collect extensive information on health, lifestyles, biological health determinants and environmental exposures. This paper will provide guidelines on how to combine health and HBM surveys and what is the added value of doing so. Health and HBM surveys utilize similar infrastructure and data collection methods including questionnaires, collection and analysis of biological samples, and objective health measurements. There are many overlapping or comparable steps in these two survey types. At the European level, detailed protocols for conducting a health examination survey or HBM study exists separately but there is no protocol for a combined survey available by now. Our recommendations for combined health and HBM surveys focus on a cross-sectional survey on general population aged 6-79 years. To avoid unnecessary participant burden, for the selection of included measurements basic principle would be to ensure that results of the measurements have a public health relevance and clear interpretation. Combining health and HBM surveys into one survey would produce an extensive database for research to support policy decisions in many fields such as public health and chemical regulations. Combined surveys are cost-effective as only one infrastructure is needed to collect information and recruit participants.This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 733032.info:eu-repo/semantics/publishedVersio

Hexamoll(R) DINCH and DPHP metabolites in urine of children and adolescents in Germany: Human biomonitoring results of the German Environmental Survey GerES V, 2014-2017

The production and use of the plasticisers Hexamoll(R) DINCH (di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate) and DPHP (di-(2-propylheptyl) phthalate) have increased after both chemicals were introduced into the market in the early 2000s as substitutes for restricted high molecular weight phthalates. During the population representative German Environmental Survey (GerES) of Children and Adolescents (GerES V, 2014–2017), we collected urine samples and measured the concentrations of DINCH and DPHP metabolites in 2228 and in a subsample of 516 participants, respectively. We detected DINCH and DPHP metabolites in 100% and 62% of the 3-17 years old children and adolescents, respectively. Geometric means of DINCH metabolites were 2.27 μg/L for OH-MINCH, 0.93 μg/L for oxo-MINCH, 1.14 μg/L for cx-MINCH and 3.47 μg/L for DINCH (Σ of OH-MINCH + cx-MINCH). Geometric means of DPHP metabolites were 0.30 μg/L for OH-MPHP, 0.32 µg/L for oxo-MPHP and 0.64 μg/L for DPHP (Σ of OH-MPHP + oxo-MPHP). The 3-5 years old children had almost 3-fold higher DINCH biomarkers levels than adolescents (14-17 years). Higher concentrations of DPHP biomarkers among young children only became apparent after creatinine adjustment. Urinary levels of DINCH but not of DPHP biomarkers were associated with the levels of the respective plasticisers in house dust. When compared to HBM health-based guidance values, we observed no exceedance of the HBM-I value of 1 mg/L for DPHP (Σ of OH-MPHP + oxo-MPHP). However, 0.04% of the children exceeded the health based guidance value HBM-I of 3 mg/L for DINCH (Σ of OH-MINCH + cx-MINCH). This finding shows that even a less toxic replacement of restricted chemicals can reach exposures in some individuals, at which, according to current knowledge, health impacts cannot be excluded with sufficient certainty. In conclusion, we provide representative data on DINCH and DPHP exposure of children and adolescents in Germany. Further surveillance is warranted to assess the substitution process of plasticisers, and to advise exposure reduction measures, especially for highly exposed children and adolescents. Providing the results to the European HBM Initiative HBM4EU will support risk assessment and risk management not only in Germany but also in Europe

Learning from previous work and finding synergies in the domains of public and environmental health: EU-funded projects BRIDGE Health and HBM4EU.

During the last decade, the European Union initiated several projects in the domains of public and environmental health. Within this framework, BRIDGE Health (Bridging Information and Data Generation for Evidence-based Health policy and Research) and HBM4EU (European human biomonitoring initiative) have been implemented. Whereas, the focus of BRIDGE Health was towards a sustainable and integrated health information system (HIS), the aim of HBM4EU is to improve evidence of the internal exposure of European citizens to environmental chemicals by human biomonitoring (HBM) and the impact of internal exposure on health. As both, environmental and public health determinants are important for health promotion, disease prevention and policy, BRIDGE Health and HBM4EU have overlapping aims and outcomes. In order to improve health information regarding public health and environmental health issues, best use and exchange of respective networks and project results is necessary. Both projects have implemented health information (HI) and HBM tasks in order to provide adequate environmental and public health information of the European population. Synergies of the projects were identified in the working progress and because of overlapping networks and experts a focused analysis of both projects was envisaged. This paper elaborates on the aims and outcomes of both projects and the benefit of merging and channelling research results for the use of better health information and policy making that may be of relevance for any other project in these research fields. The need for focused exchanges and collaborations between the projects were identified and benefits of exchanges were highlighted for the specific areas of indicator development, linkage of data repositories and the combination of HBM studies and health examination surveys (HES). Further recommendations for a European wide harmonisation among different tasks in the fields of public health and environmental health are being developed. Lessons learned from HBM4EU and BRIDGE Health show that continuous efforts must be undertaken, also by succeeding projects, to guarantee the exchange between public health and environmental health issues. Networks covering both are essential to provide better evidence of knowledge. The experiences from BRIDGE Health and HBM4EU give a valuable input for any future activity in these domains. Avoiding overlaps and streamlining further exchange of public health and environmental health contributes to best use of research results and allows to develop new strategies and tools for improvement of health information and thus enhances people's health and well-being.This publication is funded from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032 (HBM4EU) and from the Federal Ministry for the Environment, Nature Conservation and Nuclear Safety of Germany (BMU) under FKZ 3716622000. Open Access funding provided by Projekt DEAL.S

Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept

Chemical mixture risk assessment has, in the past, primarily focused on exposures quantified in the external environment. Assessing health risks using human biomonitoring (HBM) data provides information on the internal concentration, from which a dose can be derived, of chemicals to which human populations are exposed. This study describes a proof of concept for conducting mixture risk assessment with HBM data, using the population-representative German Environmental Survey (GerES) V as a case study. We first attempted to identify groups of correlated biomarkers (also known as 'communities', reflecting co-occurrence patterns of chemicals) using a network analysis approach ( n = 515 individuals) on 51 chemical substances in urine. The underlying question is whether the combined body burden of multiple chemicals is of potential health concern. If so, subsequent questions are which chemicals and which co-occurrence patterns are driving the potential health risks. To address this, a biomonitoring hazard index was developed by summing over hazard quotients, where each biomarker concentration was weighted (divided) by the associated HBM health-based guidance value (HBM-HBGV, HBM value or equivalent). Altogether, for 17 out of the 51 substances, health-based guidance values were available. If the hazard index was higher than 1, then the community was considered of potential health concern and should be evaluated further. Overall, seven communities were identified in the GerES V data. Of the five mixture communities where a hazard index was calculated, the highest hazard community contained N-Acetyl-S-(2-carbamoyl-ethyl)cysteine (AAMA), but this was the only biomarker for which a guidance value was available. Of the other four communities, one included the phthalate metabolites mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) with high hazard quotients, which led to hazard indices that exceed the value of one in 5.8% of the participants included in the GerES V study. This biological index method can put forward communities of co-occurrence patterns of chemicals on a population level that need further assessment in toxicology or health effects studies. Future mixture risk assessment using HBM data will benefit from additional HBM health-based guidance values based on population studies. Additionally, accounting for different biomonitoring matrices would provide a wider range of exposures. Future hazard index analyses could also take a common mode of action approach, rather than the more agnostic and non-specific approach we have taken in this proof of concept

Phthalate metabolites in urine of children and adolescents in Germany: human biomonitoring results of the German Environmental Survey GerES V, 2014-2017

During the population representative German Environmental Survey of Children and Adolescents (GerES V, 2014-2017) 2256 first-morning void urine samples from 3 to 17 years old children and adolescents were analysed for 21 metabolites of 11 different phthalates (di-methyl phthalate (DMP), di-ethyl phthalate (DEP), butylbenzyl phthalate (BBzP), di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), di-cyclohexyl phthalate (DCHP), di-n-pentyl phthalate (DnPeP), di-(2-ethylhexyl) phthalate (DEHP), di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP) and di-n-octyl phthalate (DnOP)). Metabolites of DMP, DEP, BBzP, DiBP, DnBP, DEHP, DiNP and DiDP were found in 97%-100% of the participants, DCHP and DnPeP in 6%, and DnOP in none of the urine samples. Geometric means (GM) were highest for metabolites of DiBP (MiBP: 26.1 μg/L), DEP (MEP: 25.8 μg/L), DnBP (MnBP: 20.9 μg/L), and DEHP (cx-MEPP: 11.9 μg/L). For all phthalates but DEP, GMs were consistently higher in the 3–5 years old children than in the 14-17 years old adolescents. For DEHP, the age differences were most pronounced. All detectable phthalate biomarker concentrations were positively associated with the levels of the respective phthalate in house dust. In GerES V we found considerably lower phthalate biomarker levels than in the preceding GerES IV (2003–2006). GMs of biomarker levels in GerES V were only 18% (BBzP), 23% (MnBP), 23% (DEHP), 29% (MiBP) and 57% (DiNP) of those measured a decade earlier in GerES IV. However, some children and adolescents still exceeded health-based guidance values in the current GerES V. 0.38% of the participants had levels of DnBP, 0.08% levels of DEHP and 0.007% levels of DiNP which were higher than the respective health-based guidance values. Accordingly, for these persons an impact on health cannot be excluded with sufficient certainty. The ongoing and substantial exposure of vulnerable children and adolescents to many phthalates confirms the need of a continued monitoring of established phthalates, whether regulated or not, as well as of potential substitutes. With this biomonitoring approach we provide a picture of current individual and cumulative exposure developments and body burdens to phthalates, thus providing support for timely and effective chemicals policies and legislation

The questionnaire design process in the European Human Biomonitoring Initiative (HBM4EU)

This document was created for the HBM4EU project. HBM4EU has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 733032. The Swiss participation in this European Program is funded by the Swiss State Secretary for Education Research and Innovation (SERI).Background: Designing questionnaires is a key point of epidemiological studies assessing human exposure to chemicals. The lack of validated questionnaires can lead to the use of previously developed and sub-optimally adapted questionnaires, which may result in information biases that affect the study’s validity. On this ground, a multidisciplinary group of researchers developed a series of tools to support data collection within the HBM4EU initiative. The objective of this paper is to share the process of developing HBM4EU questionnaires, as well as to provide researchers with harmonized procedures that could help them to design future questionnaires to assess environmental exposures. Methods: In the frame of the work package on survey design and fieldwork of the HBM4EU, researchers carried out procedures necessary for the development of quality questionnaires and related data collection tools. These procedures consisted of a systematic search to identify questionnaires used in previous human biomonitoring (HBM) studies, as well as the development of a checklist and evaluation sheet to assess the questionnaires identified. The results of these evaluations were taken into consideration for the development of the final questionnaires. Results: The main points covered by each of the sections included in HBM4EU questionnaires are described and discussed in detail. Additional tools developed for data collection in the HBM4EU (e.g. non-responder questionnaire, satisfaction questionnaire, matrix-specific questionnaire) are also addressed. Special attention is paid to the limitations faced and hurdles overcome during the process of questionnaire development. Conclusions: Designing questionnaires for use in HBM studies requires substantial effort by a multidisciplinary team to guarantee that the quality of the information collected meets the study’s objectives. The process of questionnaire development described herein will contribute to improve the harmonization of HBM studies within the social and environmental context of the EU countries.European Union's Horizon 2020 research and innovation programme 733032Swiss State Secretary for Education Research and Innovation (SERI

Scoping Review-The Association between Asthma and Environmental Chemicals

Asthma is one of the most common chronic diseases worldwide affecting all age groups from children to the elderly. In addition to other factors such as smoking, air pollution and atopy, some environmental chemicals are shown or suspected to increase the risk of asthma, exacerbate asthma symptoms and cause other respiratory symptoms. In this scoping review, we report environmental chemicals, prioritized for investigation in the European Human Biomonitoring Initiative (HBM4EU), which are associated or possibly associated with asthma. The substance groups considered to cause asthma through specific sensitization include: diisocyanates, hexavalent chromium Cr(VI) and possibly p-phenylenediamine (p-PDA). In epidemiological studies, polyaromatic hydrocarbons (PAHs) and organophosphate insecticides are associated with asthma, and phthalates, per- and polyfluoroalkyl substances (PFASs), pyrethroid insecticides, mercury, cadmium, arsenic and lead are only potentially associated with asthma. As a conclusion, exposure to PAHs and some pesticides are associated with increased risk of asthma. Diisocyanates and Cr(VI) cause asthma with specific sensitization. For many environmental chemicals, current studies have provided contradicting results in relation to increased risk of asthma. Therefore, more research about exposure to environmental chemicals and risk of asthma is needed.Peer reviewe