Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2'-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.

Biomedical Research Center 18012 Granada Spain

Biomedical Research Center 18012 Granada Spain; Department of Radiology and Physical Medicine School of Medicine University of Granada 18016 Granada Spain

Biomedical Research Center Spain

Biomedical Research Center Spain; Department of Legal Medicine and Toxicology University of Granada School of Medicine Granada Spain

Centre for Arctic Health and Molecular Epidemiology Department of Public Health Aarhus University Denmark

Centre for Arctic Health and Molecular Epidemiology Department of Public Health Aarhus University Denmark; Greenland Centre for Health Research University of Greenland Nuuk Greenland

Department of Environmental Health Norwegian Institute of Public Health Oslo Norway

Environment Agency Austria Vienna Austria

European University Cyprus Nicosia Cyprus

German Federal Institute for Risk Assessment Max Dohrn Straße 8 10 10589 Berlin Germany

Institute of Environmental Medicine Karolinska Institute Stockholm Sweden

Institute of Medical Genetics Medical University of Vienna Waehringer Strasse 10 A 1090 Vienna Austria

National Food Institute Technical University of Denmark 2800 Kgs Lyngby Denmark

National Food Institute Technical University of Denmark 2800 Kgs Lyngby Denmark; The National Research Centre for the Working Environment Copenhagen Denmark

National Institute of Health Doutor Ricardo Jorge NOVA Medical School FCM Universidade Nova de Lisboa Av Padre Cruz 1649 016 Lisbon Portugal

Physiologie Moléculaire et Adaptation Département Adaptation du Vivant UMR 7221 MNHN CNRS Muséum National d'Histoire Naturelle Paris 75005 France

RECETOX Faculty of Science Masaryk University Kamenice 5 CZ62500 Brno Czech Republic

The National Research Centre for the Working Environment Copenhagen Denmark

Univ Rennes EHESP Inserm Irset UMR_S 1085 F 35000 Rennes France

VITO Health Flemish Institute for Technological Research Mol Belgium

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

Citace poskytuje Crossref.org

Altered Transcriptome Response in PBMCs of Czech Adults Linked to Multiple PFAS Exposure: B Cell Development as a Target of PFAS Immunotoxicity