PMID- 36841007
OWN - NLM
STAT- MEDLINE
DCOM- 20230314
LR  - 20230330
IS  - 1618-131X (Electronic)
IS  - 1438-4639 (Linking)
VI  - 249
DP  - 2023 Apr
TI  - Implementation of effect biomarkers in human biomonitoring studies: A systematic 
      approach synergizing toxicological and epidemiological knowledge.
PG  - 114140
LID - S1438-4639(23)00031-7 [pii]
LID - 10.1016/j.ijheh.2023.114140 [doi]
AB  - 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.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.
FAU - Rodriguez-Carrillo, Andrea
AU  - Rodriguez-Carrillo A
AD  - Biomedical Research Center (CIBM), University of Granada, Instituto de 
      Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; 
      Department of Radiology and Physical Medicine, School of Medicine, University of 
      Granada, 18016, Granada, Spain.
FAU - Mustieles, Vicente
AU  - Mustieles V
AD  - Biomedical Research Center (CIBM), University of Granada, Instituto de 
      Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; 
      Department of Radiology and Physical Medicine, School of Medicine, University of 
      Granada, 18016, Granada, Spain; Consortium for Biomedical Research in 
      Epidemiology & Public Health (CIBERESP), Spain.
FAU - Salamanca-Fernandez, Elena
AU  - Salamanca-Fernandez E
AD  - Biomedical Research Center (CIBM), University of Granada, Instituto de 
      Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; 
      Department of Radiology and Physical Medicine, School of Medicine, University of 
      Granada, 18016, Granada, Spain. Electronic address: esalamanca@ugr.es.
FAU - Olivas-Martinez, Alicia
AU  - Olivas-Martinez A
AD  - Biomedical Research Center (CIBM), University of Granada, Instituto de 
      Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain.
FAU - Suarez, Beatriz
AU  - Suarez B
AD  - Biomedical Research Center (CIBM), University of Granada, Instituto de 
      Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain.
FAU - Bajard, Lola
AU  - Bajard L
AD  - RECETOX, Faculty of Science, Masaryk University, Kamenice 5, CZ62500, Brno, Czech 
      Republic.
FAU - Baken, Kirsten
AU  - Baken K
AD  - VITO Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
FAU - Blaha, Ludek
AU  - Blaha L
AD  - RECETOX, Faculty of Science, Masaryk University, Kamenice 5, CZ62500, Brno, Czech 
      Republic.
FAU - Bonefeld-Jorgensen, Eva Cecilie
AU  - Bonefeld-Jorgensen EC
AD  - Centre for Arctic Health & Molecular Epidemiology, Department of Public Health 
      Aarhus University, Denmark; Greenland Centre for Health Research, University of 
      Greenland, Nuuk, Greenland.
FAU - Couderq, Stephan
AU  - Couderq S
AD  - Physiologie Moleculaire et Adaptation, Departement "Adaptation du Vivant", UMR 
      7221 MNHN/CNRS, Museum National d'Histoire Naturelle, Paris, 75005, France.
FAU - D'Cruz, Shereen Cynthia
AU  - D'Cruz SC
AD  - Univ Rennes, EHESP, Inserm, Irset (Institut de Recherche en Sante, Environnement 
      et Travail) - UMR_S 1085, F-35000, Rennes, France.
FAU - Fini, Jean-Baptiste
AU  - Fini JB
AD  - Physiologie Moleculaire et Adaptation, Departement "Adaptation du Vivant", UMR 
      7221 MNHN/CNRS, Museum National d'Histoire Naturelle, Paris, 75005, France.
FAU - Govarts, Eva
AU  - Govarts E
AD  - VITO Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
FAU - Gundacker, Claudia
AU  - Gundacker C
AD  - Institute of Medical Genetics, Medical University of Vienna, Waehringer Strasse 
      10, A-1090, Vienna, Austria.
FAU - Hernandez, Antonio F
AU  - Hernandez AF
AD  - Biomedical Research Center (CIBM), University of Granada, Instituto de 
      Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; 
      Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), 
      Spain; Department of Legal Medicine and Toxicology, University of Granada School 
      of Medicine, Granada, Spain.
FAU - Lacasana, Marina
AU  - Lacasana M
AD  - Biomedical Research Center (CIBM), University of Granada, Instituto de 
      Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; 
      Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), 
      Spain; Department of Legal Medicine and Toxicology, University of Granada School 
      of Medicine, Granada, Spain.
FAU - Laguzzi, Federica
AU  - Laguzzi F
AD  - Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
FAU - Linderman, Birgitte
AU  - Linderman B
AD  - Department of Environmental Health, Norwegian Institute of Public Health, Oslo, 
      Norway.
FAU - Long, Manhai
AU  - Long M
AD  - Centre for Arctic Health & Molecular Epidemiology, Department of Public Health 
      Aarhus University, Denmark; Greenland Centre for Health Research, University of 
      Greenland, Nuuk, Greenland.
FAU - Louro, Henriqueta
AU  - Louro H
AD  - National Institute of Health Doutor Ricardo Jorge (INSA), Human Genetics 
      Department, Toxicogenomics and Human Health (ToxOmics), NOVA Medical School/FCM, 
      Universidade Nova de Lisboa, Av. Padre Cruz, 1649-016, Lisbon, Portugal.
FAU - Neophytou, Christiana
AU  - Neophytou C
AD  - European University Cyprus, Nicosia, Cyprus.
FAU - Oberemn, Axel
AU  - Oberemn A
AD  - German Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, 
      Berlin, Germany.
FAU - Remy, Sylvie
AU  - Remy S
AD  - VITO Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
FAU - Rosenmai, Anna Kjerstine
AU  - Rosenmai AK
AD  - National Food Institute, Technical University of Denmark, 2800 Kgs, Lyngby, 
      Denmark.
FAU - Saber, Anne Thoustrup
AU  - Saber AT
AD  - The National Research Centre for the Working Environment, Copenhagen, Denmark.
FAU - Schoeters, Greet
AU  - Schoeters G
AD  - VITO Health, Flemish Institute for Technological Research (VITO), Mol, Belgium; 
      Department of Biomedical Sciences and Toxicological Center, University of 
      Antwerp, Belgium.
FAU - Silva, Maria Joao
AU  - Silva MJ
AD  - National Institute of Health Doutor Ricardo Jorge (INSA), Human Genetics 
      Department, Toxicogenomics and Human Health (ToxOmics), NOVA Medical School/FCM, 
      Universidade Nova de Lisboa, Av. Padre Cruz, 1649-016, Lisbon, Portugal.
FAU - Smagulova, Fatima
AU  - Smagulova F
AD  - Univ Rennes, EHESP, Inserm, Irset (Institut de Recherche en Sante, Environnement 
      et Travail) - UMR_S 1085, F-35000, Rennes, France.
FAU - Uhl, Maria
AU  - Uhl M
AD  - Environment Agency Austria (EAA), Vienna, Austria.
FAU - Vinggaard, Anne Marie
AU  - Vinggaard AM
AD  - National Food Institute, Technical University of Denmark, 2800 Kgs, Lyngby, 
      Denmark.
FAU - Vogel, Ulla
AU  - Vogel U
AD  - National Food Institute, Technical University of Denmark, 2800 Kgs, Lyngby, 
      Denmark; The National Research Centre for the Working Environment, Copenhagen, 
      Denmark.
FAU - Wielsoe, Maria
AU  - Wielsoe M
AD  - Centre for Arctic Health & Molecular Epidemiology, Department of Public Health 
      Aarhus University, Denmark.
FAU - Olea, Nicolas
AU  - Olea N
AD  - Biomedical Research Center (CIBM), University of Granada, Instituto de 
      Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; 
      Department of Radiology and Physical Medicine, School of Medicine, University of 
      Granada, 18016, Granada, Spain; Consortium for Biomedical Research in 
      Epidemiology & Public Health (CIBERESP), Spain.
FAU - Fernandez, Mariana F
AU  - Fernandez MF
AD  - Biomedical Research Center (CIBM), University of Granada, Instituto de 
      Investigacion Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; 
      Department of Radiology and Physical Medicine, School of Medicine, University of 
      Granada, 18016, Granada, Spain; Consortium for Biomedical Research in 
      Epidemiology & Public Health (CIBERESP), Spain. Electronic address: 
      marieta@ugr.es.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230224
PL  - Germany
TA  - Int J Hyg Environ Health
JT  - International journal of hygiene and environmental health
JID - 100898843
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adolescent
MH  - Humans
MH  - *Biological Monitoring
MH  - *Brain-Derived Neurotrophic Factor
MH  - Biomarkers
MH  - Environmental Monitoring/methods
OTO - NOTNLM
OT  - Biomarkers
OT  - Effect biomarkers
OT  - Environmental chemicals
OT  - HBM4EU
OT  - Human biomonitoring programs
OT  - Occupational chemicals
EDAT- 2023/02/26 06:00
MHDA- 2023/03/15 06:00
CRDT- 2023/02/25 18:06
PHST- 2022/07/20 00:00 [received]
PHST- 2023/02/08 00:00 [revised]
PHST- 2023/02/15 00:00 [accepted]
PHST- 2023/02/26 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/02/25 18:06 [entrez]
AID - S1438-4639(23)00031-7 [pii]
AID - 10.1016/j.ijheh.2023.114140 [doi]
PST - ppublish
SO  - Int J Hyg Environ Health. 2023 Apr;249:114140. doi: 10.1016/j.ijheh.2023.114140. 
      Epub 2023 Feb 24.