Rodríguez-Carrillo Andrea, Mustieles Vicente, Salamanca-Fernández Elena, Olivas-Martínez Alicia, Suárez Beatriz, Bajard Lola, Baken Kirsten, Blaha Ludek, Bonefeld-Jørgensen Eva Cecilie, Couderq Stephan, D'Cruz Shereen Cynthia, Fini Jean-Baptiste, Govarts Eva, Gundacker Claudia, Hernández Antonio F, Lacasaña Marina, Laguzzi Federica, Linderman Birgitte, Long Manhai, Louro Henriqueta, Neophytou Christiana, Oberemn Axel, Remy Sylvie, Rosenmai Anna Kjerstine, Saber Anne Thoustrup, Schoeters Greet, Silva Maria Joao, Smagulova Fatima, Uhl Maria, Vinggaard Anne Marie, Vogel Ulla, Wielsøe Maria, Olea Nicolás, Fernández Mariana F
Biomedical Research Center (CIBM), University of Granada, Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; Department of Radiology and Physical Medicine, School of Medicine, University of Granada, 18016, Granada, Spain.
Biomedical Research Center (CIBM), University of Granada, Instituto de Investigación 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.
Int J Hyg Environ Health. 2023 Apr;249:114140. doi: 10.1016/j.ijheh.2023.114140. Epub 2023 Feb 24.
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.
人体生物监测（HBM）研究突显了人们日常广泛接触环境化学物质的情况。其中一些化学物质被怀疑会导致不良健康后果，如生殖、神经和代谢紊乱，以及其他发育和慢性损伤。“地平线2020”欧洲人体生物监测计划（HBM4EU）的目标之一是开发信息丰富的效应生物标志物，以便在大规模欧洲人体生物监测研究中以更系统、更统一的方式应用。纳入效应生物标志物将用基于机制的早期和晚期不良反应信息补充暴露数据。为此，制定了一项逐步策略，以识别并在欧洲人体生物监测研究中实施一组经过验证的效应生物标志物。这项工作概述了所遵循的完整程序，从全面的文献检索策略、效应生物标志物的选择标准及其基于毒理学数据和不良后果的分类与优先级排序，到对其进行分析、生理和流行病学验证的试点研究。我们给出一项研究的例子，该研究证明了脑源性神经营养因子BDNF的效应生物标志物状态在婴儿双酚A（BPA）暴露与青少年行为功能之间的纵向关联中起中介作用。一组效应生物标志物已在HBM4EU队列研究中作为主要结果实施，包括传统的氧化应激、生殖和甲状腺激素生物标志物。新型效应生物标志物，如BDNF和亲吻素（KISS）基因的DNA甲基化状态，也分别作为神经和生殖健康的分子标志物进行了评估。一组效应生物标志物也已应用于HBM4EU职业研究中，如淋巴细胞和网织红细胞中的微核分析、全血彗星试验，以及尿液中的丙二醛、8-氧代-2'-脱氧鸟苷和非靶向代谢组学谱，以研究例如对六价铬Cr(VI)暴露的生物学变化。在HBM4EU中使用效应生物标志物已证明它们能够检测化学物质暴露的早期生物学效应，并识别出风险较高的亚组。HBM4EU制定的路线图证实了效应生物标志物的效用，并支持HBM研究的主要目标之一，即将暴露生物标志物与经过机制验证的效应和易感性生物标志物联系起来，以便更好地理解人类接触环境化学物质对公共健康的影响。
