Phthalates are mainly used as plasticizers for polyvinyl chloride (PVC). Exposure to several phthalates is associated with different adverse effects most prominently on the development of reproductive functions. The HBM4EU Aligned Studies (2014-2021) have investigated current European exposure to ten phthalates (DEP, BBzP, DiBP, DnBP, DCHP, DnPeP, DEHP, DiNP, DiDP, DnOP) and the substitute DINCH to answer the open policy relevant questions which were defined by HBM4EU partner countries and EU institutions as the starting point of the programme. The exposure dataset includes ∼5,600 children (6-11 years) and adolescents (12-18 years) from up to 12 countries per age group and covering the North, East, South and West European regions. Study data from participating studies were harmonised with respect to sample size and selection of participants, selection of biomarkers, and quality and comparability of analytical results to provide a comparable perspective of European exposure. Phthalate and DINCH exposure were deduced from urinary excretions of metabolites, where concentrations were expressed as their key descriptor geometric mean (GM) and 95th percentile (P95). This study aims at reporting current exposure levels and differences in these between European studies and regions, as well as comparisons to human biomonitoring guidance values (HBM-GVs). GMs for children were highest for ∑DEHP metabolites (33.6 μg/L), MiBP (26.6 μg/L), and MEP (24.4 μg/L) and lowest for∑DiDP metabolites (1.91 μg/L) and ∑DINCH metabolites (3.57 μg/L). In adolescents highest GMs were found for MEP (43.3 μg/L), ∑DEHP metabolites (28.8 μg/L), and MiBP (25.6 μg/L) and lowest for ∑DiDP metabolites (= 2.02 μg/L) and ∑DINCH metabolites (2.51 μg/L). In addition, GMs and P95 stratified by European region, sex, household education level, and degree of urbanization are presented. Differences in average biomarker concentrations between sampling sites (data collections) ranged from factor 2 to 9. Compared to the European average, children in the sampling sites OCC (Denmark), InAirQ (Hungary), and SPECIMEn (The Netherlands) had the lowest concentrations across all metabolites and ESTEBAN (France), NAC II (Italy), and CROME (Greece) the highest. For adolescents, comparably higher metabolite concentrations were found in NEB II (Norway), PCB cohort (Slovakia), and ESTEBAN (France), and lower concentrations in POLAES (Poland), FLEHS IV (Belgium), and GerES V-sub (Germany). Multivariate analyses (Survey Generalized Linear Models) indicate compound-specific differences in average metabolite concentrations between the four European regions. Comparison of individual levels with HBM-GVs revealed highest rates of exceedances for DnBP and DiBP, with up to 3 and 5%, respectively, in children and adolescents. No exceedances were observed for DEP and DINCH. With our results we provide current, detailed, and comparable data on exposure to phthalates in children and - for the first time - in adolescents, and - for the first time - on DINCH in children and adolescents of all four regions of Europe which are particularly suited to inform exposure and risk assessment and answer open policy relevant questions.

Constantine the Philosopher University in Nitra Slovakia

Department of Growth and Reproduction Copenhagen University Hospital Rigshospitalet Copenhagen Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Medicine DAME University of Udine Udine Italy

Environmental Engineering Laboratory Department of Chemical Engineering Aristotle University of Thessaloniki Thessaloniki Greece; HERACLES Research Center on the Exposome and Health Center for Interdisciplinary Research and Innovation Thessaloniki Thermi Greece

Environmental Engineering Laboratory Department of Chemical Engineering Aristotle University of Thessaloniki Thessaloniki Greece; HERACLES Research Center on the Exposome and Health Center for Interdisciplinary Research and Innovation Thessaloniki Thermi Greece; Environmental Health Engineering Institute of Advanced Study Pavia Italy

German Environment Agency Berlin Germany

Institute for Maternal and Child Health IRCCS Burlo Garofolo Trieste Italy

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

IST Clinical Pharmacology Pharmacy and Environmental Medicine Odense Denmark

Jozef Stefan Institute Department of Environmental Sciences Ljubljana Slovenia

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

National Institute for Public Health and the Environment Bilthoven the Netherlands

National Public Health Center Budapest Hungary

Nofer Institute of Occupational Medicine Lodz Poland

Norwegian Institute of Public Health Oslo Norway

RECETOX Faculty of Science Masaryk University Brno Czech Republic

Santé publique France Environmental and Occupational Health Division Saint Maurice France

Slovak Medical University Faculty of Public Health Bratislava Slovakia

Swedish Food Agency Uppsala Sweden

Toxicological Center University of Antwerp Wilrijk Belgium

VITO Health Flemish Institute for Technological Research Mol Belgium

VITO Health Flemish Institute for Technological Research Mol Belgium; University of Antwerp Dept of Biomedical Sciences and Toxicological Centre Antwerp Belgium

Citace poskytuje Crossref.org

Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative

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