From science to policy: How European HBM indicators help to answer policy questions related to phthalates and DINCH exposure.

Within the European Human Biomonitoring (HBM) Initiative HBM4EU we derived HBM indicators that were designed to help answering key policy questions and support chemical policies. The result indicators convey information on chemicals exposure of different age groups, sexes, geographical regions and time points by comparing median exposure values. If differences are observed for one group or the other, policy measures or risk management options can be implemented. Impact indicators support health risk assessment by comparing exposure values with health-based guidance values, such as human biomonitoring guidance values (HBM-GVs). In general, the indicators should be designed to translate complex scientific information into short and clear messages and make it accessible to policy makers but also to a broader audience such as stakeholders (e.g. NGO's), other scientists and the general public. Based on harmonized data from the HBM4EU Aligned Studies (2014-2021), the usefulness of our indicators was demonstrated for the age group children (6-11 years), using two case examples: one phthalate (Diisobutyl phthalate: DiBP) and one non-phthalate substitute (Di-isononyl cyclohexane-1,2- dicarboxylate: DINCH). For the comparison of age groups, these were compared to data for teenagers (12-18 years), and time periods were compared using data from the DEMOCOPHES project (2011-2012). Our result indicators proved to be suitable for demonstrating the effectiveness of policy measures for DiBP and the need of continuous monitoring for DINCH. They showed similar exposure for boys and girls, indicating that there is no need for gender focused interventions and/or no indication of sex-specific exposure patterns. They created a basis for a targeted approach by highlighting relevant geographical differences in internal exposure. An adequate data basis is essential for revealing differences for all indicators. This was particularly evident in our studies on the indicators on age differences. The impact indicator revealed that health risks based on exposure to DiBP cannot be excluded. This is an indication or flag for risk managers and policy makers that exposure to DiBP still is a relevant health issue. HBM indicators derived within HBM4EU are a valuable and important complement to existing indicator lists in the context of environment and health. Their applicability, current shortcomings and solution strategies are outlined.

A human biomonitoring (HBM) Global Registry Framework: Further advancement of HBM research following the FAIR principles.

Data generated by the rapidly evolving human biomonitoring (HBM) programmes are providing invaluable opportunities to support and advance regulatory risk assessment and management of chemicals in occupational and environmental health domains. However, heterogeneity across studies, in terms of design, terminology, biomarker nomenclature, and data formats, limits our capacity to compare and integrate data sets retrospectively (reuse). Registration of HBM studies is common for clinical trials; however, the study designs and resulting data collections cannot be traced easily. We argue that an HBM Global Registry Framework (HBM GRF) could be the solution to several of challenges hampering the (re)use of HBM (meta)data. The aim is to develop a global, host-independent HBM registry framework based on the use of harmonised open-access protocol templates from designing, undertaking of an HBM study to the use and possible reuse of the resulting HBM (meta)data. This framework should apply FAIR (Findable, Accessible, Interoperable and Reusable) principles as a core data management strategy to enable the (re)use of HBM (meta)data to its full potential through the data value chain. Moreover, we believe that implementation of FAIR principles is a fundamental enabler for digital transformation within environmental health. The HBM GRF would encompass internationally harmonised and agreed open access templates for HBM study protocols, structured web-based functionalities to deposit, find, and access harmonised protocols of HBM studies. Registration of HBM studies using the HBM GRF is anticipated to increase FAIRness of the resulting (meta)data. It is also considered that harmonisation of existing data sets could be performed retrospectively. As a consequence, data wrangling activities to make data ready for analysis will be minimised. In addition, this framework would enable the HBM (inter)national community to trace new HBM studies already in the planning phase and their results once finalised. The HBM GRF could also serve as a platform enhancing communication between scientists, risk assessors, and risk managers/policy makers. The planned European Partnership for the Assessment of Risk from Chemicals (PARC) work along these lines, based on the experience obtained in previous joint European initiatives. Therefore, PARC could very well bring a first demonstration of first essential functionalities within the development of the HBM GRF.

Chemical prioritisation strategy in the European Human Biomonitoring Initiative (HBM4EU) - Development and results.

The 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.

A call for urgent action to safeguard our planet and our health in line with the helsinki declaration.

In 2015, the Rockefeller Foundation-Lancet Commission launched a report introducing a novel approach called Planetary Health and proposed a concept, a strategy and a course of action. To discuss the concept of Planetary Health in the context of Europe, a conference entitled: "Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health" was held in Helsinki in December 2019. The conference participants concluded with a need for action to support Planetary Health during the 2020s. The Helsinki Declaration emphasizes the urgency to act as scientific evidence shows that human activities are causing climate change, biodiversity loss, land degradation, overuse of natural resources and pollution. They threaten the health and safety of human kind. Global, regional, national, local and individual initiatives are called for and multidisciplinary and multisectorial actions and measures are needed. A framework for an action plan is suggested that can be modified for local needs. Accordingly, a shift from fragmented approaches to policy and practice towards systematic actions will promote human health and health of the planet. Systems thinking will feed into conserving nature and biodiversity, and into halting climate change. The Planetary Health paradigm ‒ the health of human civilization and the state of natural systems on which it depends ‒ must become the driver for all policies.

Measurement of ethyl glucuronide, ethyl sulphate and their ratio in the urine and serum of healthy volunteers after two doses of alcohol.

AIMS: Ethyl glucuronide (EtG) and ethyl sulphate (EtS) are minor metabolites of ethanol, and their presence in urine provides a strong indication of recent alcohol administration. In this study, we performed a drinking experiment to investigate the kinetics of EtG and EtS formation and elimination after the administration of two doses of alcohol. METHODS: Nineteen volunteers provided urine and serum (only 18) after administration of 4 and 8 units of alcohol (1 unit corresponds to 10 ml or ∼8 g of pure ethanol). The analysis was performed using a validated ultra-performance liquid chromatography-mass spectrometry (UPLC(®)-MS/MS) method. RESULTS: After 4 units, the median EtG maximum concentration (C(max)) was 0.4 µg/ml and the interquartile range (0.3 µg/ml) in serum and 3.5 mg/h (1.2 mg/h) in urine and were reached (T(max)) after 2.0 h (0.8 h) and 3.0 h (1.0 h), respectively. EtS C(max) was 0.2 µg/ml (0.1 µg/ml) in serum and 1.3 mg/h (0.6 mg/h) in urine, and the corresponding T(max) were 1.0 h (1.0 h) and 2.0 h (0.5 h). After 8 units, EtG C(max) was 1.3 µg/ml (0.4 µg/ml) in serum and 10 mg/h (3.4 mg/h) in urine and was reached after 4.0 h (1.8 h) and 4.0 h (2.0 h), respectively. EtS C(max) was 0.6 µg/ml (0.1 µg/ml) in serum and 3.5 mg/h (1.1 mg/h) in urine, the corresponding T(max) were 3.0 h (1.0 h) and 3.0 h (1.0 h). The EtG/EtS ratio increased as a function of the time after alcohol administration in both serum and urine samples but to a lesser extent after 8 units than 4. CONCLUSION: These results correlate with values obtained in previous studies. T(max) of EtG and EtS increased between 4 and 8 units. The EtG:EtS ratio increased in the serum and urine samples of all volunteers as a function of time at least up to 4 h after alcohol administration.