Albumin adducts and urinary metabolites resulting from occupational exposure to 1,5-naphthalene diisocyanate

Objectives: 1,5-Naphthalene diisocyanate (NDI) is used in the plastic industry as a curing agent. 1,5-Naphthalene diisocyanate is classified as a sensitizing agent. The objective of this study has been to develop biomonitoring methods for the evaluation of exposure to NDI. Material and Methods: We obtained blood and urine samples from a group of 20 male workers exposed to NDI. The workers answered a questionnaire about their exposure history, job description, the number of years with the company and the time spent working with NDI over the 10 days of the study. Total plasma, albumin, and urine were analyzed for the presence of 1,5-naphthalenediamine (NDA) after acid hydrolysis using gas chromatography-mass spectrometry (GC-MS). Results: 1,5-Naphthalenediamine was found in about 60% of the samples obtained from the workers. 1,5-Naphthalenediamine was obtained after acid hydrolysis of plasma, albumin, and urine at levels up to 1.5 pmol NDA/mg of plasma proteins, 1.15 pmol NDA/mg of albumin, and 55.3 pmol NDA/ml of urine, respectively. Conclusions: 1,5-Naphthalenediamine found in urine correlates best with the plasma levels (r = 0.91, p < 0.01). The albumin-adduct levels did not correlate with the NDI-specific immunoglobulin E (IgE) or total IgE present in the workers. The adduct and metabolite levels correlate with the air levels of NDI

Comparison of Hemoglobin Binding, Mutagenicity, and Carcinogenicity of Arylamines and Nitroarenes

N-Oxidation and nitro-reduction which yield N-hydroxyarylamines are metabolic steps that are crucial for the genotoxic and toxic properties of aromatic amines and nitroarenes, respectively. N-Hydroxyarylamines form adducts with DNA, tissue proteins, and blood proteins. Except for nine compounds, it has been shown that after treatment of rats with nitroarenes (n = 31) or arylamines (n = 36) hydrolyzable hemoglobin adducts are formed as a result of the formation of the potentially genotoxic intermediate, N-hydroxyarylamine. Therefore, hemoglobin adducts are a good dosimeter of human exposure to a large array of arylamines and nitroarenes. The amount of hemoglobin binding decreases with the oxidizability of the arylamines, except for compounds which are substituted with halogens in the ortho- and/or meta-position. For halogen-substituted arylamines, the amount of hemoglobin binding is directly proportional to the pKa. The level of hemoglobin binding and mutagenicity is directly proportional to the reducibility of the nitroarenes, but hemoglobin binding and mutagenicity do not correlate. In general the mutagenicity or carcinogenicity of arylamines increases with their oxidizability. This first set of data suggests that the levels of hemoglobin binding, mutagenicity, and carcinogenicity of arylamines are not determined by the same electronic properties of the compounds, or not by these properties alone. These results indicate that hemoglobin binding may prove not to be a useful index of the genotoxic potency of arylamines and nitroarenes. Further work is needed to investigate the relationship between hemoglobin binding and cytotoxicity of these compounds. However, the prospect that other blood proteins might be more suitable as biomarkers for biological effects of nitroarenes and arylamines needs to be investigated

Human biomonitoring data interpretation and ethics; obstacles or surmountable challenges?

The use of human samples to assess environmental exposure and uptake of chemicals is more than an analytical exercise and requires consideration of the utility and interpretation of data as well as due consideration of ethical issues. These aspects are inextricably linked

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

Consultation on a sustainable HBM initiative in Europe - Deliverable Report D6.3 WP6 Sustainability and Capacity building.

This deliverable was produced under Task 6.3 of Work Package 6 on “Longer-term needs and expectations of stakeholders (2021-2030)”. The aim of this task was to gather information on the needs and expectations of both the National Hubs (NH) and a broad range of stakeholders regarding a long-term Human Biomonitoring (HBM) programme for Europe, to be establish in follow up to the current project, HBM4EU. Firstly and with a focus on options for financing a future initiative, information was collected on a range of available funding mechanisms at national, regional and international level. In terms of national funding, the results presented rely on responses to a survey with the NH. Unfortunately, the response from NHs was very limited, and as such the report only captures funding mechanisms from a limited number of countries, including Portugal, Spain, France, Germany and Cyprus. In order to gain insight into the status of the National Hubs and their capacities for HBM, a survey was conducted. The results provide an overview of the current situation across the NHs with regards to a range of aspects, including the level of activity of the NH, status of political support, availability of funding, ongoing HBM studies and willingness to align studies with HBM4EU. The results suggest that HBM4EU has raised the political profile of HBM in partner countries. Regarding ongoing HBM studies, only six countries have national HBM programmes, with most countries having only hot spot studies. Despite this, there was support for the alignment of studies to achieve European geographical coverage. Regarding funding, access to European funding is seen as important to leverage funds at national level. A second survey was targeted at a wide range of stakeholders, aiming to better understand their expectations for a long-term sustainable HBM initiative. The survey was followed by a workshop, where a more limited number of stakeholders had the opportunity to discuss the survey results and address such aspects as the scope of a future initiative, how to achieve financial sustainability, how to involve and how a future initiative might contribute to chemical policies. Concerning the needs and expectations of stakeholders, there is a strong interest in and support for a future HBM initiative at European level. The involvement of a European Union (EU) institution as part of a future steering committee was seen as crucial. According to this stakeholders’ consultation, the initiative should focus on protecting human health and the environment in Europe from hazardous chemical exposures by producing harmonised, high quality, transparent and inclusive data for effective risk assessment and management.HBM4EU - Grant agreement 733032 HORIZON 2020 Programmeinfo:eu-repo/semantics/publishedVersio

Chemical exposure : european citizens’ perspectives, trust, and concerns on human biomonitoring initiatives, information needs, and scientific results

Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Over the last few decades, citizen awareness and perception of chemical products has been a topic of interest, particularly concerning national and international policy decision makers, expert/scientific platforms, and the European Union itself. To date, few qualitative studies on human biomonitoring have analysed communication materials, made recommendations in terms of biomonitoring surveillance, or asked for feedback in terms of specific biomonitoring methods. This paper provides in-depth insight on citizens’ perceptions of knowledge of biomonitoring, impact of chemical exposure on daily life, and claims on how results of research should be used. Four semi-structured focus groups were held in Austria, Portugal, Ireland, and the United Kingdom (UK). The cross-sectional observational qualitative design of this study allows for better understanding of public concern regarding chemicals, application, and use of human biomonitoring. The main findings of this study include citizens’ clear articulation on pathways of exposure, the demand on stakeholders for transparent decision-making, and sensitivity in communication of results to the public. Validated and trustful communication is perceived as key to empowering citizens to take action. The results can be used to facilitate decision-making and policy development, and feeds into the awareness needs of similar and future projects in human biomonitoring. Furthermore, it also brings to light ideas and concepts of citizens’ in shaping collaborative knowledge between citizens’, experts, scientists, and policy makers on equal terms.The HBM4EU project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 73303info:eu-repo/semantics/publishedVersio

WP6 - Sustainability and Capacity building

This report aims to provide a revision on the national needs (T6.1), the funding mechanisms (T6.2) and the long-term sustainability of HBM4EU (T6.3). Therefore, this report is divided in the three above-mentioned sections, for which the different tasks within work package 6 (WP 6) provided input. Concerning national needs, a survey is conducted annually by the national hub (NH) coordinator to monitor and evaluate the progress and development of all National Hubs involved in HBM4EU. With 2020 being the fourth year of the HBM4EU project, the survey followed many of the questions of previous years. Most NHs are satisfied with their current HBM4EU involvement, but have expressed their concerns regarding the communication, funding and lack of direct involvement. The follow-up to HBM4EU, PARC, was mentioned and the necessary involvement of all countries as well as the importance of communication between NHs and National Hub Contact Points (NHCPs) was highlighted. Inclusivity of smaller countries seems to be a problem through both lack of funding and adequate tasks. Regarding funding mechanisms, the initial list of financing mechanisms in the HBM and environmental health area at national and international level was updated and is available on the HBM4EU website under the “Funding Opportunities” tab. This intends to be an inventory that can be used not only by the HBM4EU consortium but by the entire scientific community to provide an overview of existing funding sources. It comprises of a set of targeted strategies for identification and dissemination of funding which are explained in further detail in section 6 Funding mechanisms. A systematic literature review was also undertaken to understand what the primary funding source of projects in HBM was. The results are not available yet. As part of T6.3 on the long-term sustainability, a citizen survey was developed together with T4.1 – mapping of needs. This survey was initially used for focus groups to better understand their awareness and concerns of chemical exposure and Human Biomonitoring. It was updated to harvest more EU-wide results including chemical exposure during the COVID-19 pandemic. The survey took place between September 2020 and February 2021 and the results were organised to cover the same regions as the aligned studies to allow for the organisation of results in a similar way for coherence. In order to produce a short report summarising the outcome of the survey, the questions were grouped for quicker analysis. The majority of the respondents considers HBM a tool that produces important results on human exposure to chemicals and that it should be performed more often and in a more coordinated way. This was a non-representative survey and future work should focus on wider dissemination in other population groups and on understanding how perceptions change over time. The survey’s answers were also distributed to the NHs, so they can produce internal communication briefs on their own data for further dissemination.HORIZON2020 Programme Contract No. 733032 HBM4EU.info:eu-repo/semantics/publishedVersio

HBM4EU combines and harmonises human biomonitoring data across the EU, building on existing capacity - The HBM4EU survey

As part of the Human Biomonitoring for Europe (HBM4EU) initiative a human biomonitoring (HBM) survey is conducted in 21 countries. This survey builds on existing HBM capacity in Europe by aligning national or regional HBM studies. The survey targets 3 age groups (i) children aged 6-11 years, (ii) teenagers aged 12-19 years and (iii) young adults aged 20-39 years and includes a total of 9493 participants (3151 children, 2953 teenagers and 3389 young adults). Depending on the age group, internal exposure to phthalates and substitute Hexamoll® DINCH, brominated and organophosphorus flame retardants, per-/poly-fluorinated compounds, cadmium, bisphenols and/or polycyclic aromatic hydrocarbons are assessed. The main goal of the programme is to obtain quality controlled and comparable HBM data of exposure to chemicals, prioritized under HBM4EU, with European wide coverage to inform the development of environment and health policies. This paper describes the framework of the HBM4EU survey and the approach that has been applied to align European HBM initiatives across Europe.HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). The authors thank all principle investigators of the contributing studies for their participation and contribution to the joint HBM4EU survey and the national programme owners for their financial support. In addition we want to thank Dr. Liesbeth Bruckers and Dr. Michael Schümann.S

Challenges to evidence synthesis and identification of data gaps in human biomonitoring

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).The increasing number of human biomonitoring (HBM) studies undertaken in recent decades has brought to light the need to harmonise procedures along all phases of the study, including sampling, data collection and analytical methods to allow data comparability. The first steps towards harmonisation are the identification and collation of HBM methodological information of existing studies and data gaps. Systematic literature reviews and meta-analyses have been traditionally put at the top of the hierarchy of evidence, being increasingly applied to map available evidence on health risks linked to exposure to chemicals. However, these methods mainly capture peer-reviewed articles, failing to comprehensively identify other important, unpublished sources of information that are pivotal to gather a complete map of the produced evidence in the area of HBM. Within the framework of the European Human Biomonitoring Initiative (HBM4EU) initiative-a project that joins 30 countries, 29 from Europe plus Israel, the European Environment Agency and the European Commission-a comprehensive work of data triangulation has been made to identify existing HBM studies and data gaps across countries within the consortium. The use of documentary analysis together with an up-to-date platform to fulfil this need and its implications for research and practice are discussed.HBM4EU has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032.info:eu-repo/semantics/publishedVersio

reflection and lessons learnt from designing and undertaking a collaborative European biomonitoring study on occupational exposure to hexavalent chromium

The EU human biomonitoring initiative, HBM4EU, aims to co-ordinate and advance human biomonitoring (HBM) across Europe. As part of HBM4EU, we presented a protocol for a multicentre study to characterize occupational exposure to hexavalent chromium (Cr(VI)) in nine European countries (HBM4EU chromates study). This study intended to collect data on current occupational exposure and to test new indicators for chromium (Cr) biomonitoring (Cr(VI) in exhaled breath condensate and Cr in red blood cells), in addition to traditional urinary total Cr analyses. Also, data from occupational hygiene samples and biomarkers of early biological effects, including genetic and epigenetic effects, was obtained, complementing the biomonitoring information. Data collection and analysis was completed, with the project findings being made separately available. As HBM4EU prepares to embark on further European wide biomonitoring studies, we considered it important to reflect on the experiences gained through our harmonised approach. Several practical aspects are highlighted for improvement in future studies, e.g., more thorough/earlier training on the implementation of standard operating procedures for field researchers, training on the use of the data entry template, as well as improved company communications. The HBM4EU chromates study team considered that the study had successfully demonstrated the feasibility of conducting a harmonised multicentre investigation able to achieve the research aims and objectives. This was largely attributable to the engaged multidisciplinary network, committed to deliver clearly understood goals. Such networks take time and investment to develop, but are priceless in terms of their ability to deliver and facilitate knowledge sharing and collaboration.publishersversionpublishe