Suchergebnisse

We thank our other HBM4EU colleagues (mentioned as co-authors in Mustieles et al., 2020) for their contribution to the first literature searches. ; Bisphenols, particularly bisphenol A (4,40 -(hexafluoroisopropylidene)-diphenol) (BPA), are suspected of inducing oxidative stress in humans, which may be associated with adverse health outcomes. We investigated the associations between exposure to bisphenols and biomarkers of oxidative stress in human studies over the last 12 years (2008-2019) related to six health endpoints and evaluated their suitability as effect biomarkers. PubMed database searches identified 27 relevant articles that were used for data extraction. In all studies, BPA exposure was reported, whereas some studies also reported other bisphenols. More than a dozen different biomarkers were measured. The most frequently measured biomarkers were 8-oxo-7,8-dihydro-20 -deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoprostane) and malondialdehyde (MDA), which almost always were positively associated with BPA. Methodological issues were reported for MDA, mainly the need to handle samples with caution to avoid artefact formation and its measurements using a chromatographic step to distinguish it from similar aldehydes, making some of the MDA results less reliable. Urinary 8-OHdG and 8-isoprostane can be considered the most reliable biomarkers of oxidative stress associated with BPA exposure. Although none of the biomarkers are considered BPAor organ-specific, the biomarkers can be assessed repeatedly and non-invasively in urine and could help to understand causal relationships. ; HBM4EU project - European Union's Horizon 2020 research and innovation program 733032

Humans are exposed to a large number of chemicals from sources such as the environment, food, and consumer products. There is growing concern that human exposure to chemical mixtures, especially during critical periods of development, increases the risk of adverse health effects in newborns or later in life. Historically, the onechemical-at-a-time approach has been applied both for exposure assessment and hazard characterisation, leading to insufficient knowledge about human health effects caused by exposure to mixtures of chemicals that have the same target. To circumvent this challenge researchers can apply in vitro assays to analyse both exposure to and human health effects of chemical mixtures in biological samples. The advantages of using in vitro assays are: (i) that an integrated effect is measured, taking combined mixture effects into account and (ii) that in vitro assays can reduce complexity in identification of Chemicals of Emerging Concern (CECs) in human tissues. We have reviewed the state-of-the-art on the use of receptor-based in vitro assays to assess human exposure to chemical mixtures and related health impacts. A total of 43 studies were identified, in which endpoints for the arylhydrocarbon receptor (AhR), the estrogen receptor (ER), and the androgen receptor (AR) were used. The majority of studies reported biological activities that could be associated with breast cancer incidence, male reproductive health effects, developmental toxicities, human demographic characteristics or lifestyle factors such as dietary patterns. A few studies used the bioactivities to check the coverage of the chemical analyses of the human samples, whereas in vitro assays have so far not regularly been used for identifying CECs in human samples, but rather in environmental matrices or food packaging materials. A huge field of novel applications using receptor-based in vitro assays for mixture toxicity assessment on human samples and effect-directed analysis (EDA) using high resolution mass spectrometry (HRMS) for identification of toxic compounds waits for exploration. In the future this could lead to a paradigm shift in the way we unravel adverse human health effects caused by chemical mixtures. ; European Union's Horizon 2020 research and innovation programme HBM4EU 733032

The authors thank the European Union's Horizon 2020 research and innovation programme HBM4EU under Grant Agreement No. 733032 for its financial support. Vicente Mustieles and Stephan Couderq are under contract within the HBM4EU project. Additionally, we acknowledge the Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP), and the Instituto de Salud Carlos III (ISCIII) (FIS-PI16/01820 and FIS-PI16/01858). The authors also thank the ISCIII and "Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) for the Sara Borrell postdoctoral research contract granted to F. Vela-Soria (grant no. CD17/00212), and the Spanish Ministry of Education for the predoctoral fellowship (FPU) granted to A. Rodríguez-Carrillo (FPU 16/03011). This article will be part of the doctoral thesis developed by Andrea Rodríguez-Carrillo in the context of the "Clinical Medicine and Public Health Program" of the University of Granada (Spain). The authors gratefully acknowledge the technical assistance of Birgitte Møller Plesning. ; Humans are simultaneously exposed to complex mixtures of chemicals with limited knowledge on potential health effects, therefore improved tools for assessing these mixtures are needed. As part of the Human Bio-monitoring for Europe (HBM4EU) Project, we aimed to examine the combined biological activity of chemical mixtures extracted from human placentas using one in vivo and four in vitro bioassays, also known as biomarkers of combined effect. Relevant endocrine activities (proliferative and/or reporter gene assays) and four endpoints were tested: the estrogen receptor (ER), androgen receptor (AR), and aryl hydrocarbon receptor (AhR) activities, as well as thyroid hormone (TH) signaling. Correlations among bioassays and their functional shapes were evaluated. Results showed that all placental extracts agonized or antagonized at least three of the above-mentioned endpoints. Most placentas induced ER-mediated transactivation and ER-dependent cell proliferation, together with a strong ...

This research would not have been achieved without the selfless collaboration of the INMA-Granada adolescents and families who took part in the study. The authors also acknowledge the Human Genotyping Laboratory at the Spanish National Cancer Research Center, CeGen-PRB3, which is supported by grant no. PT17/0019, of the PE I+D+i 2013-2016, funded by the Instituto de Salud Carlos III (ISCIII) and ERDF. They thank the European Union's Horizon 2020 research and innovation program HBM4EU for financial support under Grant Agree-ment No. 733032. The study was also supported by the ISCIII with grant no. CP16/00085. The authors also acknowledge the funding received from the University of Granada for the open access publishing costs and the support of the Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP) , and the ISCIII (FIS 17/01526, FIS-PI16/01820 and FIS-PI16/01858) . Vicente Mustieles and Shereen Cynthia D'Cruz were under contract with the HBM4EU project. A. Rodriguez-Carrillo received a predoctoral fellowship (FPU 16/03011) from the Spanish Ministry of Education and C. Freire (grant no. MS16/00085) received a grant under the Miguel Servet Type I program of the ISCIII "Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) . This article forms part of the doctoral thesis developed by Andrea Rodriguez-Carrillo in the context of the "Clinical Medicine and Public Health Program" of the University of Granada (Spain) . ; Background: Brain-derived neurotrophic factor (BDNF) plays an important role in brain development by regulating multiple pathways within the central nervous system. In the Human Biomonitoring for Europe Project (HBM4EU), this neurotrophin is being implemented as a novel effect biomarker to evaluate the potential threats of environmental chemicals on neurodevelopment. Objectives: To explore the relationships among exposure to environmental metals, BDNF biomarkers at two levels of biological complexity, and behavioral function in adolescent males. Methods: Data were ...

Human biomonitoring (HBM) studies have demonstrated widespread and daily exposure to bisphenol A (BPA). Moreover, BPA structural analogues (e.g. BPS, BPF, BPAF), used as BPA replacements, are being increasingly detected in human biological matrices. BPA and some of its analogues are classified as endocrine disruptors suspected of contributing to adverse health outcomes such as altered reproduction and neurodevelopment, obesity, and metabolic disorders among other developmental and chronic impairments. One of the aims of the H2020 European Human Biomonitoring Initiative (HBM4EU) is the implementation of effect biomarkers at large scales in future HBM studies in a systematic and standardized way, in order to complement exposure data with mechanistically-based biomarkers of early adverse effects. This review aimed to identify and prioritize existing biomarkers of effect for BPA, as well as to provide relevant mechanistic and adverse outcome pathway (AOP) information in order to cover knowledge gaps and better interpret effect biomarker data. A comprehensive literature search was performed in PubMed to identify all the epidemiologic studies published in the last 10 years addressing the potential relationship between bisphenols exposure and alterations in biological parameters. A total of 5716 references were screened, out of which, 119 full-text articles were analyzed and tabulated in detail. This work provides first an overview of all epigenetics, gene transcription, oxidative stress, reproductive, glucocorticoid and thyroid hormones, metabolic and allergy/immune biomarkers previously studied. Then, promising effect biomarkers related to altered neurodevelopmental and reproductive outcomes including brain-derived neurotrophic factor (BDNF), kisspeptin (KiSS), and gene expression of nuclear receptors are prioritized, providing mechanistic insights based on in vitro, animal studies and AOP information. Finally, the potential of omics technologies for biomarker discovery and its implications for risk assessment are discussed. To the best of our knowledge, this is the first effort to comprehensively identify bisphenol-related biomarkers of effect for HBM purposes. ; This work is a direct product of the Human Biomonitoring for Europe Project (European Union Commission H2020-EJP-HBM4EU Grant agreement No 733032). V. Mustieles, S.C. D'Cruz and S. Couderq are under contract within the HBM4EU Initiative. ; Yes

This research would not have been achieved without the selfless collaboration of the INMA-Granada adolescents and families who took part in the study. The authors acknowledge the European Union's Horizon 2020 research and innovation program HBM4EUfor the financial support under Grant Agreement #733032. The study was also supported by the ISCIII with grants no. CP16/00085 and FIS 17/01526, and the Human Genotyping Laboratory at the Spanish National Cancer Research Center (CeGen-PRB3). The authors also thank the support of the Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP), and the University of Granada (Grant "UNETE," UCE-PP2017-06). A. Rodriguez-Carrillo received a predoctoral fellowship (FPU 16/03011) from the Spanish Ministry of Education, Spain, and Vicente Mustieles and Shereen Cynthia D'Cruz were under contract with the HBM4EUproject. C. Freire received a grant under the Miguel Servet Type I program of the ISCIII "Fondo Europeo de Desarrollo Regional" (MS16/00085; ISCIII/FEDER). This article forms part of the doctoral thesis developed by Andrea Rodriguez-Carrillo in the context of the "Clinical Medicine and Public Health Program" of the University of Granada (Spain). ; Background: Numerous contemporary non-persistent pesticides may elicit neurodevelopmental impairments. Brain-derived neurotrophic factor (BDNF) has been proposed as a novel effect biomarker of neurological function that could help to understand the biological responses of some environmental exposures. Objectives: To investigate the relationship between exposure to various non-persistent pesticides, BDNF, and behavioral functioning among adolescents. Methods: The concentrations of organophosphate (OP) insecticide metabolites 3,5,6-trichloro-2-pyridinol (TCPy), 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy), malathion diacid (MDA), and diethyl thiophosphate (DETP); metabolites of pyrethroids 3-phenoxybenzoic acid (3-PBA) and dimethylcyclopropane carboxylic acid (DCCA), the metabolite of insecticide ...

This research would not have been achieved without the selfless col-laboration of the INMA-Granada boys and families who took part in the study. Vicente Mustieles, Alicia Olivas-Martinez and Shereen Cynthia D'Cruz were under contract within the HBM4EU project. Additionally, we acknowledge the Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP) , and the Instituto de Salud Carlos III (ISCIII) (FIS-PI16/01820, FIS-PI16/01858, FIS-PI17/01526, and FIS-PI20/01568) . The authors also thank the ISCIII and "Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) for the Miguel Servet Type I Program granted to C. Freire (grant no. MS16/00085) , the Sara Borrell postdoctoral research contract granted to F. Vela-Soria (grant no. CD17/00212) , and the Spanish Ministry of Education for the predoctoral fellowships (FPU) granted to A. Rodriguez-Carrillo (FPU 16/03011) and to I. Reina-Perez (FPU 17/01848) . Dr. JP Arrebola is under contract within the Ramon y Cajal Program (RYC-2016-20155, from Ministerio de Economia, Industria y Competitividad, Spain) . The authors also ac-knowledge the contribution of the Pediatric Unit of San Cecilio University Hospital of Granada (recruitment and clinical evaluation) , Marina Molina (field work and biospecimen processing) , Raquel Quesada and Beatriz Suarez (chemical exposure data) and Mario Murcia (data curation) , as well as the Human Genotyping Laboratory at the Spanish National Cancer Research Centre, CeGen-PRB3, which is sup-ported by grant no. PT17/0019, of the PE I + D + i 2013-2016, funded by Instituto de Salud Carlos III (ISCIII) and ERDF. This article will be part of the doctoral thesis developed by Andrea Rodriguez-Carrillo in the context of the "Clinical Medicine and Public Health Program" of the University of Granada (Spain) . ; This study was supported in part by the European Union's Horizon 2020 research and innovation program HBM4EU [Grant Agreement No. 733032], Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública ...