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

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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

Human health effects of benzene, arsenic, cadmium, nickel, lead and mercury: Report of an expert consultation

Ana Isabel Cañas Portilla y Argelia Castaño Calvo del Centro Nacional de Sanidad Ambiental (ISCIII) han participado en este informe como expertos proporcionando comentarios técnicos.Benzene, arsenic, cadmium, lead, mercury and nickel are ubiquitous pollutants in ambient air. The main sources are industrial processes, electricity generation and fuel combustion. The main routes of exposure are inhalation for benzene, and diet for arsenic, cadmium, lead, nickel and mercury. Inhalation of benzene, arsenic and cadmium is relevant for exposure in active tobacco smokers and people exposed to second-hand tobacco smoke. Epidemiological studies show that exposure to these pollutants is associated with adverse effects on the cardiovascular (cadmium, lead, mercury); haematological (benzene, lead); immunological, neurological and reproductive (benzene, lead, mercury); respiratory (cadmium, nickel); renal (cadmium, lead); and skeletal (cadmium) systems. Limited epidemiological evidence on ambient air pollution suggests adverse effects on the cardiovascular system (arsenic and nickel). Since benzene, arsenic, cadmium and nickel are classified as carcinogenic, the lowest possible exposure level is suggested to minimize the risk for cancer development in view of the no-effect threshold paradigm. Lead and methylmercury compounds are classified as possibly carcinogenic to humans. However, the available evidence is insufficient to warrant updating the air quality guidelines for these air pollutants. Evidence gaps are identified and these should guide future research efforts.S

Serum PCB levels in a representative sample of the Spanish adult population: the BIOAMBIENT.ES project

This manuscript presents the levels of six indicator polychlorinated biphenyl (PCB) congeners (IUPAC nos. 28, 52, 101, 138, 153 and 180) in the serum of 1880 individuals from a representative sample of the Spanish working population recruited between March 2009 and July 2010. Three out of the six PCBs studied (180, 153 and 138) were quantified in more than 99% of participants. PCB 180 was the highest contributor, followed by PCBs 153 and 138, with relative abundances of 42.6%, 33.2% and 24.2%, respectively. In contrast, PCBs 28 and 52 were detected in only 1% of samples, whereas PCB 101 was detectable in 6% of samples. The geometric mean (GM) for ΣPCBs138/153/180 was 135.4 ng/g lipid (95% CI: 121.3-151.2 ng/g lipid) and the 95th percentile was 482.2 ng/g lipid. Men had higher PCB blood concentrations than women (GMs 138.9 and 129.9 ng/g lipid respectively). As expected, serum PCB levels increased with age and frequency of fish consumption, particularly in those participants younger than 30 years of age. The highest levels we found were for participants from the Basque Country, whereas the lowest concentrations were found for those from the Canary Islands. The Spanish population studied herein had similar levels to those found previously in Greece and southern Italy, lower levels than those in France and central Europe, and higher PCB levels than those in the USA, Canada and New Zealand. This paper provides the first baseline information regarding PCB exposure in the Spanish adult population on a national scale. The results will allow us to establish reference levels, follow temporal trends and identify high-exposure groups, as well as monitor implementation of the Stockholm Convention in Spain.This work was funded as part of a research agreement between the Spanish Ministry of Agriculture, Food and the Environment n° EG042007 and the Institute of Health Carlos III (project nos. SEG 1251/07 and 1210/10). The authors would like to thank S. González for the technical assistance, F. Cutanda for the helpful advice, and Silvia Gómez; the volunteers of BIOAMBIENT.ES and healthcare staff from the Societies for Prevention of IBERMUTUAMUR, MUTUALIA, MCPREVENCIÓN, MUGATRA, UNIMAT PREVENCIÓN, and PREVIMAC

Critical review of analytical methods for the determination of flame retardants in human matrices

Human biomonitoring is a powerful approach in assessing exposure to environmental pollutants. Flame retardants (FRs) are of particular concern due to their wide distribution in the environment and adverse health effects. This article reviews studies published in 2009-2020 on the chemical analysis of FRs in a variety of human samples and discusses the characteristics of the analytical methods applied to different FR biomarkers of exposure, including polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), novel halogenated flame retardants (NHFRs), bromophenols, incl. tetrabromobisphenol A (TBBPA), and organophosphorous flame retardants (PFRs). Among the extraction techniques, liquid-liquid extraction (LLE) and solid phase extraction (SPE) were used most frequently due to the good efficiencies in the isolation of the majority of the FR biomarkers, but with challenges for highly lipophilic FRs. Gas chromatography-mass spectrometry (GC-MS) is mainly applied in the instrumental analysis of PBDEs and most NHFRs, with recent inclusions of GC-MS/MS and high resolution MS techniques. Liquid chromatography-MS/MS is mainly applied to HBCD, bromophenols, incl. TBBPA, and PFRs (including metabolites), however, GC-based analysis following derivatization has also been used for phenolic compounds and PFR metabolites. Developments are noticed towards more universal analytical methods, which enable widening method scopes in the human biomonitoring of FRs. Challenges exist with regard to sensitivity required for the low concentrations of FRs in the general population and limited sample material for some human matrices. A strong focus on quality assurance/quality control (QA/QC) measures is required in the analysis of FR biomarkers in human samples, related to their variety of physical-chemical properties, low levels in most human samples and the risk of contamination.This study was part of the HBM4EU project receiving funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 733032. The authors acknowledge Berith E. Knudsen for her help with the literature search.S

Human biomonitoring. Basics: educational course

Ana Isabel Cañas Portilla, Argelia Castaño, Susana Pedraza Diaz y Marta Esteban López del Centro Nacional de Sanidad Ambiental (ISCIII) han contribuido en el desarrollo de este curso.Human biomonitoring (HBM) is an instrument for measuring the internal dose of exogenous substances/chemicals that enter a body during a certain period of exposure from a range of sources. It contributes to reducing uncertainties in the assessment of health risks from chemicals and provides information for decision-making on the prevention of negative impacts of chemicals on human health and the environment. Promoting the use of HBM is a recognized priority of chemical safety globally and in the WHO European Region. Given the complexity of HBM, relevant capacities should be built at the national level to explore its benefits. This educational course on HBM, presented in the form of slides with accompanying notes and references, compiles scientific information on HBM as well as practical examples. It was developed to support the training of public-health and health-care professionals; students of medical, biological and other allied sciences; and professionals and decision-makers in the health, environment and other relevant sectorsThis course was developed with financial support from the German Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection and the German Federal Ministry of Health.S

Personal care product use and lifestyle affect phthalate and DINCH metabolite levels in teenagers and young adults

Humans are widely exposed to phthalates and their novel substitutes, and considering the negative health effects associated with some phthalates, it is crucial to understand population levels and exposure determinants. This study is focused on 300 urine samples from teenagers (aged 12-17) and 300 from young adults (aged 18-37) living in Czechia collected in 2019 and 2020 to assess 17 plasticizer metabolites as biomarkers of exposure. We identified widespread phthalate exposure in the study population. The diethyl phthalate metabolite monoethyl phthalate (MEP) and three di (2-ethylhexyl) phthalate metabolites were detected in the urine of >99% of study participants. The highest median concentrations were found for metabolites of low-molecular-weight (LMW) phthalates: mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP) and MEP (60.7; 52.6 and 17.6 μg/L in young adults). 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) metabolites were present in 68.2% of the samples with a median of 1.24 μg/L for both cohorts. Concentrations of MnBP and MiBP were similar to other European populations, but 5-6 times higher than in populations in North America. We also observed large variability in phthalate exposures within the study population, with 2-3 orders of magnitude differences in urinary metabolites between high and low exposed individuals. The concentrations varied with season, gender, age, and lifestyle factors. A relationship was found between high levels of MEP and high overall use of personal care products (PCPs). Cluster analysis suggested that phthalate exposures depend on season and multiple lifestyle factors, like time spent indoors and use of PCPs, which combine to lead to the observed widespread presence of phthalate metabolites in both study populations. Participants who spent more time indoors, particularly noticeably during colder months, had higher levels of high-molecular weight phthalate metabolites, whereas participants with higher PCP use, particularly women, tended to have higher concentration of LMW phthalate metabolites.Authors thank the Research Infrastructure RECETOX RI (No. LM2018121) and CETOCOEN EXCELLENCE (CZ.02.1.01/0.0/0.0/17_043/0009632) for a supportive background. The work was supported by the Operational Programme Research, Development and Innovation – project Cetocoen Plus (CZ.02.1.01/0.0/0.0/15_003/0000469) and the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 857560. This study has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 733032. We thank all collaborating field workers, laboratory and administrative personnel, and especially the cohort participants who invested their time and provided samples and information for this study. This study reflects only the authors’ view and the European Commission is not responsible for any use that may be made of the information it contains.S

Coordination of chemical analyses under the European Human Biomonitoring Initiative (HBM4EU): Concepts, procedures and lessons learnt

The European Human Biomonitoring Initiative (HBM4EU) ran from 2017 to 2022 with the aim of advancing and harmonizing human biomonitoring in Europe. More than 40,000 analyses were performed on human samples in different human biomonitoring studies in HBM4EU, addressing the chemical exposure of the general population, temporal developments, occupational exposure and a public health intervention on mercury in populations with high fish consumption. The analyses covered 15 priority groups of organic chemicals and metals and were carried out by a network of laboratories meeting the requirements of a comprehensive quality assurance and control system. The coordination of the chemical analyses included establishing contacts between sample owners and qualified laboratories and monitoring the progress of the chemical analyses during the analytical phase, also addressing status and consequences of Covid-19 measures. Other challenges were related to the novelty and complexity of HBM4EU, including administrative and financial matters and implementation of standardized procedures. Many individual contacts were necessary in the initial phase of HBM4EU. However, there is a potential to develop more streamlined and standardized communication and coordination in the analytical phase of a consolidated European HBM programme.This study was part of the HBM4EU project receiving funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032. The co-funding of the HBM4EU partner countries is gratefully acknowledged. The authors thank all sample owners and qualified laboratories for the excellent collaboration. The authors also acknowledge the HBM4EU partners in charge of upstream (WP7, WP8) and downstream (WP10) processes for the smooth connections with the analytical phase.S