Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledge

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Authors

RODRIGUEZ-CARRILLO Andrea MUSTIELES Vicente SALAMANCA-FERNANDEZ Elena OLIVAS-MARTINEZ Alicia SUAREZ Beatriz BAJARD ÉP.ESNER Lola Murielle BAKEN Kirsten BLÁHA Luděk BONEFELD-JORGENSEN Eva Cecilie COUDERQ Stephan CRUZ Shereen Cynthia FINI Jean-Baptiste GOVARTS Eva GUNDACKERJ Claudia HERNANDEZ Antonio F. LACASANA Marina LAGUZZI Federica LINDERMAN Birgitte LONG Manhai LOURO Henriqueta NEOPHYTOU Christiana OBEREMN Axel REMY Sylvie ROSENMAI Anna Kjerstine SABERR Anne Thoustrup SCHOETERS Greet SILVAN Maria Joao SMAGULOVA Fatima UHL Maria VINGGAARD Anne Marie VOGEL Ulla WIELSOE Maria OLEAA Nicolas FERNANDEZA Mariana F.

Year of publication 2023
Type Article in Periodical
Magazine / Source International Journal of Hygiene and Environmental Health
MU Faculty or unit

Faculty of Science

Citation
Web https://www.sciencedirect.com/science/article/pii/S1438463923000317?via%3Dihub
Doi http://dx.doi.org/10.1016/j.ijheh.2023.114140
Keywords Biomarkers; Effect biomarkers; Human biomonitoring programs; HBM4EU; Environmental chemicals; Occupational chemicals
Attached files
Description 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 vali-dated 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 toxi-cological 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 con-firms 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 un-derstand the public health implications of human exposure to environmental chemicals.
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