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Veröffentlichung Chemical prioritisation strategy in the European Human Biomonitoring Initiative (HBM4EU) - Development and results(2021) Ougier, Eva; David, Madlen; Ganzleben, Catherine; Lecoq, Pierre; Kolossa-Gehring, Marike; Lange, RosaThe European Human Biomonitoring Initiative (HBM4EU1) has established a European Union-wide human biomonitoring (HBM) programme to generate knowledge on human internal exposure to chemical pollutants and their potential health impacts in Europe, in order to support policy makers' efforts to ensure chemical safety and improve health in Europe. A prioritisation strategy was necessary to determine and meet the most important needs of both policy makers and risk assessors, as well as common national needs of participating countries and a broad range of stakeholders. This strategy consisted of three mains steps: 1) mapping of knowledge gaps identified by policy makers, 2) prioritisation of substances using a scoring system, and 3) generation of a list of priority substances reflective of the scoring, as well as of public policy priorities and available resources. For the first step, relevant ministries and agencies at EU and national levels, as well as members of the Stakeholder Forum each nominated up to 5 substances/substance groups of concern for policy-makers. These nominations were collated into a preliminary list of 48 substances/substance groups, which was subsequently shortened to a list of 23 after considering the total number of nominations each substance/substance group received and the nature of the nominating entities. For the second step, a panel of 11 experts in epidemiology, toxicology, exposure sciences, and occupational and environmental health scored each of the substances/substance groups using prioritisation criteria including hazardous properties, exposure characteristics, and societal concern. The scores were used to rank the 23 substances/substance groups. In addition, substances were categorised according to the level of current knowledge about their hazards, extent of human exposure (through the availability of HBM data), regulatory status and availability of analytical methods for biomarker measurement. Finally, in addition to the ranking and categorisation of the substances, the resources available for the project and the alignment with the policy priorities at European level were considered to produce a final priority list of 9 substances/substance groups for research activities and surveys within the framework of the HBM4EU project. Quelle: © 2021 The Authors. Published by Elsevier GmbHVeröffentlichung Human biomonitoring initiative (HBM4EU): Human biomonitoring guidance values (HBM-GVs) derived for bisphenol A(2021) Ougier, Eva; Zeman, Florence; Apel, Petra; Antignac, Jean-Philippe; Kolossa-Gehring, Marike; Lange, RosaThe "European Human Biomonitoring Initiative" (HBM4EU) derives human biomonitoring guidance values (HBM-GVs) for the general population (HBM-GVGenPop) and/or for occupationally exposed adults (HBM-GVWorker) for several priority substances and substance groups as identified by policy makers, scientists and stakeholders at EU and national level, including bisphenol A (BPA). Human exposure to BPA is widespread and of particular concern because of its known endocrine-disrupting properties. Unlike the conjugated forms of BPA circulating in the body, free BPA is known to interact with the nuclear estrogen receptors. Because free BPA is considered to be more toxicologically active than the conjugated forms (e.g. BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S)), its measurement in blood provides the superior surrogate of the biologically effective dose. However, considering the difficulty of implementing blood sampling in large HBM cohorts, as well as the current analytical capacities complying with the quality assurance (QA)/quality control (QC) schemes, total BPA in urine (i.e. the sum of free and conjugated forms of BPA measured after an hydrolysis of phase II metabolites) was retained as the relevant exposure biomarker for BPA. HBM-GVGenPop for total BPA in urine of 230 (my)g/L and 135 (my)g/L for adults and children, respectively, were developed on the basis of toxicological data. To derive these values, the concentrations of urinary total BPA consistent with a steady-state exposure to the temporary Tolerable Daily Intake (t-TDI) of 4 my/kg bw/day set in 2015 by the European Food Safety Authority (EFSA) were estimated. The BPA human physiologically-based pharmacokinetic (PBPK) model developed by Karrer et al. (2018) was used, assuming an oral exposure to BPA at the t-TDI level averaged over 24 h. Dermal uptake of BPA is suspected to contribute substantially to the total BPA body burden, which in comparison with the oral route, is generating a higher ratio of free BPA to total BPA in blood. Therefore, an alternative approach for calculating the HBM-GVGenPop according to the estimated relative contributions of both the oral and dermal routes to the global BPA exposure is also discussed. Regarding BPA exposure at the workplace, the steady-state concentration of urinary total BPA was estimated after a dermal uptake of BPA that would generate the same concentration of free BPA in plasma (considered as the bioactive form) as would a 24 h-averaged intake to the European Chemicals Agency (ECHA)'s oral DNEL of 8 (my)g BPA/kg bw/day set for workers. The predicted concentration of urinary total BPA at steady-state is equivalent to, or exceeds the 95th percentile of total BPA in urine measured in different European HBM studies conducted in the general population. Thus, no HBM-GVWorker was proposed, as the high background level of BPA coming from environmental exposure - mostly through food intake - is making the discrimination with the occupational exposure to BPA difficult. © 2021 The Author(s)Veröffentlichung Human biomonitoring initiative (HBM4EU): Human biomonitoring guidance values (HBM-GVs) derived for cadmium and its compounds(2021) Lamkarkach, Farida; Apel, Petra; Ougier, Eva; Garnier, Robert; Kolossa-Gehring, Marike; Lange, RosaAims The methodology agreed within the framework of the HBM4EU project is used in this work to derive HBM-GVs for the general population (HBM-GVGenPop) and for workers (HBM-GVWorker) exposed to cadmium (Cd) and its compounds. Methods For Cd, a significant number of epidemiological studies with doseââą Ìresponse relationships are available, in particular for kidney effects. These effects are described in terms of a relation between urinary Cd (U-Cd) or blood Cd (B-Cd) levels and low molecular weight proteinuria (LMWP) markers like beta-2-microglobulin (Î22M) and retinol-binding protein (RBP). In order to derive HBM-GVs for the general population and workers, an assessment of data from evaluations conducted by national or international organisations was undertaken. In this work, it appeared relevant to select renal effects as the critical effect for the both groups, however, differences between general population (including sensitive people) and workers (considered as an homogenous population of adults who should not be exposed to Cd if they suffer from renal diseases) required the selection of different key studies (i.e. conducted in general population for HBM-GVGenPop and at workplace for HBM-GVWorker). Results and conclusions For U-Cd, a HBM-GVGenPop of 1 (my)g/g creatinine (creat) is recommended for adults older than 50 years, based on a robust meta-analysis performed by EFSA (EFSA, 2009a). To take into account the accumulation of Cd in the human body throughout life, threshold or 'alert' values according to age were estimated for U-Cd. At workplace, a HBM-GVWorker of 2 (my)g/g creat is derived from the study of Chaumont et al., (2011) for U-Cd, and in addition to this recommendation a HBM-GVworker for B-Cd of 5 Ìg/L is also proposed. The HBM-GVWorker for U-Cd is similar to the biological limit value (BLV) set by the new amendment of the European Carcinogens and Mutagens Directive in June 2019 (2 (my)g/g creat for U-Cd). © 2021 The AuthorsVeröffentlichung Strategies for health interpretation(2018) Ougier, Eva; Apel, Petra; Lange, Rosa