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.

Constantine the Philosopher University in Nitra Tr A Hlinku 1 94901 Nitra Slovakia

Department of Medicine DAME University of Udine Via Colugna 50 33100 Udine Italy

Department of Public Health University of Copenhagen Øster Farimagsgade 5 DK Copenhagen Denmark

Environmental Engineering Laboratory Department of Chemical Engineering Aristotle University of Thessaloniki 54124 Thessaloniki Greece; HERACLES Research Center on the Exposome and Health Center for Interdisciplinary Research and Innovation Balkan Center Bldg B 10th km Thessaloniki Thermi Road 57001 Greece

Environmental Engineering Laboratory Department of Chemical Engineering Aristotle University of Thessaloniki 54124 Thessaloniki Greece; HERACLES Research Center on the Exposome and Health Center for Interdisciplinary Research and Innovation Balkan Center Bldg B 10th km Thessaloniki Thermi Road 57001 Greece; Environmental Health Engineering Institute of Advanced Study Palazzo del Broletto Piazza Della Vittoria 15 27100 Pavia Italy

European Environment Agency Kongens Nytorv 6 1050 Copenhagen Denmark

Faculty of Health Sciences Department of Public Health Clinical Pharmacology Pharmacy and Environmental Medicine University of Southern Denmark Odense Denmark

German Environment Agency Corrensplatz 1 14195 Berlin Germany

Institute for Maternal and Child Health IRCCS Burlo Garofolo 34137 Trieste Italy

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Institute of the Ruhr University Bochum 44789 Bochum Germany

Institute for Risk Assessment Sciences Utrecht University Utrecht the Netherlands

Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

Jožef Stefan Institute Department of Environmental Sciences Jamova cesta 39 1000 Ljubljana Slovenia

Luxembourg Institute of Science and Technology Department 41 rue du Brill L 4422 Belvaux Luxembourg

National Centre for Environmental Health Instituto de Salud Carlos 3 Madrid Spain

National Institute for Public Health and the Environment Bilthoven the Netherlands

National Institute of Public Health Prague Czech Republic

National Public Health Center Albert Flórián út 2 6 1097 Budapest Hungary

Nofer Institute of Occupational Medicine St Teresy 8 Lodz Poland

Norwegian Institute of Public Health Oslo Norway

Provincial Institute of Hygiene Antwerp Belgium

Public Health Authority of the Slovak Republic Trnavska cesta 52 826 45 Bratislava Slovakia

RECETOX Faculty of Science Masaryk University Kotlarska 2 Brno Czech Republic

RECETOX Faculty of Science Masaryk University Kotlarska 2 Brno Czech Republic; Faculty of Sport Studies Masaryk University Kamenice 753 5 Brno Czech Republic

Santé publique France French Public Health Agency Saint Maurice France

Slovak Medical University Faculty of Public Health Limbova 12 83303 Bratislava Slovakia

Swedish Food Agency PO Box 622 SE 751 26 Uppsala Sweden

Toxicological Center University of Antwerp 2610 Wilrijk Belgium

VITO Flemish Institute for Technological Research Unit Health Boeretang 200 2400 Mol Belgium

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