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24 results on '"MESH: Endocrine Disruptors"'

1. Regulatory and academic studies to derive reference values for human health: The case of bisphenol S

Author

Sakina Mhaouty-Kodja, Nicolas Chevalier, Sylvie Babajko, René Habert, Claire Beausoleil, Brigitte Le Magueresse-Battistoni, Catherine Viguié, Nicole Picard-Hagen, Marie-Chantal Canivenc-Lavier, Claude Emond, Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Côte d'Azur (UCA), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Université Sorbonne Paris Cité (USPC), Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Mhaouty-Kodja, Sakina

Subjects
Male, Swine, Bisphenol S, Physiology, Biological Availability, 010501 environmental sciences, Biology, Endocrine Disruptors, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Human health, Phenols, Reference Values, MESH: Policy Making, Policy making, media_common.cataloged_instance, Animals, Humans, Sulfones, European union, Benzhydryl Compounds, 030304 developmental biology, 0105 earth and related environmental sciences, General Environmental Science, media_common, 0303 health sciences, Potential impact, Toxicity, 3. Good health, Bioavailability, MESH: Endocrine Disruptors, [SDV.TOX] Life Sciences [q-bio]/Toxicology, chemistry, Reference values, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Health-based guidance value, Female, Endocrine-disrupting chemical, Target organ, hormones, hormone substitutes, and hormone antagonists
Abstract

We would like to thank the HBM4EU team including Petra Apel (UBA), Matthieu Meslin and Christophe Rousselle (Anses) for their scientific contribution, as well as the ANSES Working Group on endocrine disruption, and its scientific Anses coordinators François Pouzaud and Sandrine Charles.; International audience; The close structural analogy of bisphenol (BP) S with BPA, a recognized endocrine-disrupting chemical and a substance of very high concern in the European Union, highlights the need to assess the extent of similarities between the two compounds and carefully scrutinize BPS potential toxicity for human health. This analysis aimed to investigate human health toxicity data regarding BPS, to find a point of departure for the derivation of human guidance values. A systematic and transparent methodology was applied to determine whether European or international reference values have been established for BPS. In the absence of such values, the scientific literature on human health effects was evaluated by focusing on human epidemiological and animal experimental studies. The results were analyzed by target organ/system: male and female reproduction, mammary gland, neurobehavior, and metabolism/obesity. Academic experimental studies were analyzed and compared to regulatory data including subchronic studies and an extended one-generation and reproduction study. In contrast to the regulatory studies, which were performed at dose levels in the mg/kg bw/day range, the academic dataset on specific target organs or systems showed adverse effects for BPS at much lower doses (0.5-10 μg/kg bw/day). A large disparity between the lowest-observed-adverse-effect levels (LOAELs) derived from regulatory and academic studies was observed for BPS, as for BPA. Toxicokinetic data on BPS from animal and human studies were also analyzed and showed a 100-fold higher oral bioavailability compared to BPA in a pig model. The similarities and differences between the two bisphenols, in particular the higher bioavailability of BPS in its active (non-conjugated) form and its potential impact on human health, are discussed. Based on the available experimental data, and for a better human protection, we propose to derive human reference values for exposure to BPS from the N(L)OAELs determined in academic studies.

Published
2022
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2. Endocrine disrupting chemicals and metabolic disorders in the liver: What if we also looked at the female side?

Author

Brigitte Le Magueresse-Battistoni, Team1 Carmen, Carmen Lab, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Le Magueresse-Battistoni, Brigitte

Subjects
Male, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], 0208 environmental biotechnology, Physiology, MESH: Metabolic Diseases, 02 engineering and technology, Endocrine Disruptors, 010501 environmental sciences, Gut flora, 01 natural sciences, Energy homeostasis, Endocrine disrupting chemicals, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, biology, Organic chemicals, Fatty liver, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Pollution, 3. Good health, MESH: Endocrine Disruptors, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Liver, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Female, Adult, Environmental Engineering, medicine.drug_class, Endocrine System, Gut microbiota, Sex-dimorphism, Metabolic Diseases, medicine, Humans, Environmental Chemistry, Endocrine system, MESH: Endocrine System, Growth hormone, 0105 earth and related environmental sciences, MESH: Humans, Public Health, Environmental and Occupational Health, MESH: Quality of Life, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Lipid metabolism, MESH: Adult, General Chemistry, medicine.disease, biology.organism_classification, Estrogen, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, 020801 environmental engineering, Sexual dimorphism, Quality of Life, MESH: Female, MESH: Liver
Abstract

International audience; Endocrine disrupting chemicals (EDCs) are linked to the worldwide epidemic incidence of metabolic disorders and fatty liver diseases, which affects quality of life and represents a high economic cost to society. Energy homeostasis exhibits strong sexual dimorphic traits, and metabolic organs respond to EDCs depending on sex, such as the liver, which orchestrates both drug elimination and glucose and lipid metabolism. In addition, fatty liver diseases show a strong sexual bias, which in part could also originate from sex differences observed in gut microbiota. The aim of this review is to highlight significant differences in endocrine and metabolic aspects of the liver, between males and females throughout development and into adulthood. It is also to illustrate how the male and female liver differently cope with exposure to various EDCs such as bisphenols, phthalates and persistent organic chemicals in order to draw attention to the need to include both sexes in experimental studies. Interesting data come from analyses of the composition and diversity of the gut microbiota in males exposed to the mentioned EDCs showing significant correlations with hepatic lipid accumulation and metabolic disorders but information on females is lacking or incomplete. As industrialization increases, the list of anthropogenic chemicals to which humans will be exposed will also likely increase. In addition to strengthening existing regulations, encouraging populations to protect themselves and promoting the substitution of harmful chemicals with safe products, innovative strategies based on sex differences in the gut microbiota and in the gut-liver axis could be optimistic outlook.

Published
2021
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3. Biomonitoring of fast-elimination endocrine disruptors - Results from a 6-month follow up on human volunteers with repeated urine and hair collection

Author

François Faÿs, Paul Palazzi, Serge Haan, Emilie M. Hardy, Brice M.R. Appenzeller, Claire Beausoleil, Luxembourg Institute of Health (LIH), University of Luxembourg [Luxembourg], Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), François Faÿs benefited from a Ph.D. grant from the Luxembourg National Research Fund (Fonds National de la Recherche [FNR]) (AFR16 11262468), Luxembourg., and FNR (AFR16 11262468) / ANSES (French Agency for Food, Environmental and Occupational Health & Safety) [sponsor]

Subjects
010504 meteorology & atmospheric sciences, Limit of detection, Physiology, Urine analysis, Urine, 010501 environmental sciences, Endocrine Disruptors, 01 natural sciences, chemistry.chemical_compound, Biomonitoring, Medicine, MESH: Healthy Volunteers, Waste Management and Disposal, Gas chromatography, integumentary system, Phthalate, MESH: Follow-Up Studies, Pollution, Healthy Volunteers, MESH: Endocrine Disruptors, Endocrine disruptor, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Pharmacie, pharmacologie & toxicologie [D20] [Sciences de la santé humaine], Limit of quantifications, Environmental Exposure/analysis, Month follow up, Biological Monitoring, Environmental Engineering, MESH: Environmental Exposure, Liquid chromatography, Phthalic Acids, Bisphenol S BPS, Biomarkers of exposure, Environmental Chemistry, Endocrine system, Humans, Bisphenol F BPF, 0105 earth and related environmental sciences, business.industry, Data interpretation, Environmental Exposure, MESH: Phthalic Acids, Bisphenol A BPA, chemistry, Human exposure, Pharmacy, pharmacology & toxicology [D20] [Human health sciences], MESH: Biological Monitoring, business, Hair, Follow-Up Studies
Abstract

BACKGROUND: The assessment of human exposure to fast-elimination endocrine disruptors (ED) such as phthalates, bisphenols or pesticides is usually based on urinary biomarkers. The variability of biomarkers concentration, due to rapid elimination from the body combined with frequent exposure is however pointed out as a major limitation to exposure assessment. Other matrices such as hair, less sensitive to short-term variations in the exposure, have been proposed as possible alternatives. Nevertheless, no study compared the information obtained from hair and urine respectively in a follow-up allowing to assess biomarkers variability over time in these two matrices, and to compare the correlation between them. METHODS: In the present study, hair and urine samples were collected from 16 volunteers over a 6 months follow-up. All in all, 92 hair samples and 805 urines samples were collected and analyzed for the presence of 16 phthalate metabolites, 4 bisphenols and 8 pesticides/metabolites. RESULTS: All the biomarkers analyzed were detected in at least one of the two matrices. 21 biomarkers were more frequently detected in hair, 6 in urine, and 1 was equivalent. Biomarkers intraclass correlation coefficients (ICC) ranged from 0.1 to 0.8 (ten above 0.4) in hair, and from 0.09 to 0.51 in urine (two above 0.4). The concentrations of biomarkers in hair and urine were significantly correlated for only one compound. CONCLUSION: This study highlights the complexity of assessing exposure to fast-elimination ED and suggests considering with caution the specificity of the matrix in data interpretation. The results document the respective advantages and limitations of urine and hair, and provide new insight in the understanding of the information provided by these biological matrices and their relevance for the assessment of human exposure to fast elimination contaminants. CAPSULE: 92 hair and 805 urine samples collected from 16 volunteers over 6 months, tested for phthalate metabolites, bisphenols and pesticides. 19 biomarkers (in hair) and 24 (in urine) were detected in >50% of the samples.

Published
2021
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4. The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds

Author

Legler, Juliette, Zalko, Daniel, Jourdan, Fabien, Jacobs, Miriam, Fromenty, Bernard, Balaguer, Patrick, Bourguet, William, Munic Kos, Vesna, Nadal, Angel, Beausoleil, Claire, Cristobal, Susana, Remy, Sylvie, Ermler, Sibylle, Margiotta-Casaluci, Luigi, Griffin, Julian L., Blumberg, Bruce, Chesné, Christophe, Hoffmann, Sebastian, Andersson, Patrik L., Kamstra, Jorke H., Dep Population Health Sciences, IRAS OH Toxicology, dIRAS RA-1, Utrecht University [Utrecht], Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre for Radiation, Chemical and Environmental Hazards, Public Health England [London], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Biochimie Structurale [Montpellier] (CBS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska Institutet [Stockholm], Universidad Miguel Hernández [Elche] (UMH), Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Linköping University (LIU), Flemish Institute for Technological Research (VITO), Department of Life Sciences, College of Health and Life Sciences, Brunel University London [Uxbridge], Imperial College London, University of California [Irvine] (UCI), University of California, Biopredic International [Saint-Grégoire], Seh consulting, Umeå University, Department of Chemistry, European Union's Horizon 2020 research and innovation program under grant agreement GOLIATH No. 825489., Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of California (UC), Umeå University, European Project: 825489,H2020,GOLIATH(2019), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 825489, Horizon 2020, inrae, LESUR, Hélène, Beating Goliath: Generation Of NoveL, Integrated and Internationally Harmonised Approaches for Testing Metabolism Disrupting Compounds - GOLIATH - - H20202019-01-19 - 2023-12-31 - 825489 - VALID, Dep Population Health Sciences, IRAS OH Toxicology, and dIRAS RA-1

Subjects
0301 basic medicine, obesity, [SDV]Life Sciences [q-bio], risk assessment, 010501 environmental sciences, Endocrine Disruptors, MESH: Risk Assessment, 01 natural sciences, lcsh:Chemistry, Adverse Outcome Pathway, Adipocytes, chemicals, MESH: Obesity, lcsh:QH301-705.5, MESH: Fatty Liver, Spectroscopy, diabetes, Biochemistry and Molecular Biology, General Medicine, Integrated approach, Farmakologi och toxikologi, 3. Good health, Computer Science Applications, MESH: Endocrine Disruptors, [SDV] Life Sciences [q-bio], [SDV.TOX] Life Sciences [q-bio]/Toxicology, Risk analysis (engineering), [SDV.TOX]Life Sciences [q-bio]/Toxicology, Metabolic Networks and Pathways, Project Report, MESH: Diabetes Mellitus, endocrine, 0699 Other Biological Sciences, Pharmacology and Toxicology, Catalysis, Inorganic Chemistry, 03 medical and health sciences, 0399 Other Chemical Sciences, Diabetes Mellitus, Genetics, Humans, Physical and Theoretical Chemistry, Molecular Biology, MESH: Adipocytes, Metabolic and endocrine, 0105 earth and related environmental sciences, Metabolic health, Nutrition, 0604 Genetics, Chemical Physics, Organic Chemistry, Estrogen, Fatty Liver, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, 13. Climate action, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Business, Other Biological Sciences, Other Chemical Sciences, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biokemi och molekylärbiologi
Abstract

International audience; The purpose of this project report is to introduce the European "GOLIATH" project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as "metabolism Int. Int. J. Mol. Sci. 2020, 21, 3480 2 of 18 disrupting compounds" (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world's first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption-hepatocytes, pancreatic endocrine cells, myocytes and adipocytes-and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development.

Published
2020
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5. Endocrine disrupting potential of replacement flame retardants – Review of current knowledge for nuclear receptors associated with reproductive outcomes

Author

Johanna Barthelemy-Berneron, Lola Bajard, Vicente Mustieles, Ludek Blaha, Stéphane Jomini, Mariana F. Fernández, Chander K. Negi, Lisa Emily Melymuk, Research Centre for Toxic Compounds in the Environment [Brno] (RECETOX / MUNI), Faculty of Science [Brno] (SCI / MUNI), Masaryk University [Brno] (MUNI)-Masaryk University [Brno] (MUNI), CIBER de Epidemiología y Salud Pública (CIBERESP), Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), The research was supported by funding from the European Unionś Horizon 2020 Research and Innovation Programme under grant agreements No 733032 (HBM4EU), No. 859891 (PRORISK), and No. 857560 (CETOCOEN EXCELLENCE Teaming 2 project). The RECETOX Research infrastructure was further supported by the Czech Ministry of Education, Youth and Sports (LM2018121, CZ02.1.01/0.0/0.0/18_046/0015975)., and European Project: 733032,H2020,HBM4EU(2017)

Subjects
animal structures, 010504 meteorology & atmospheric sciences, medicine.drug_class, Endocrine disruption, Population, Receptors, Cytoplasmic and Nuclear, MESH: Receptors, Cytoplasmic and Nuclear, Endocrine Disruptors, 010501 environmental sciences, MESH: Flame Retardants, MESH: Reproduction, Bioinformatics, Flame retardants, 01 natural sciences, Phosphates, Nuclear receptors, Steroid hormones, Emerging contaminants, ToxCast, medicine, Humans, Endocrine system, GE1-350, education, Flame Retardants, 0105 earth and related environmental sciences, General Environmental Science, education.field_of_study, MESH: Humans, business.industry, Reproduction, Research needs, MESH: Endocrine Disruptors, 3. Good health, Environmental sciences, Rapid identification, Nuclear receptor, Estrogen, [SDV.TOX]Life Sciences [q-bio]/Toxicology, MESH: Phosphates, business, Systematic search
Abstract

The research was supported by funding from the European Unions ' Horizon 2020 Research and Innovation Programme under grant agreements No 733032 (HBM4EU) , No. 859891 (PRORISK) , and No. 857560 (CETOCOEN EXCELLENCE Teaming 2 project) . The RECETOX Research infrastructure was further supported by the Czech Ministry of Education, Youth and Sports (LM2018121; CZ02.1.01/0.0/0.0/18_046/0015975) ., Background and aim: Endocrine disrupting chemicals (EDCs) constitute a major public health concern because they can induce a large spectrum of adverse effects by interfering with the hormonal system. Rapid identification of potential EDCs using in vitro screenings is therefore critical, particularly for chemicals of emerging concerns such as replacement flame retardants (FRs). The review aimed at identifying (1) data gaps and research needs regarding endocrine disrupting (ED) properties of replacement FRs and (2) potential EDCs among these emerging chemicals. Methods: A systematic search was performed from open literature and ToxCast/Tox21 programs, and results from in vitro tests on the activities of 52 replacement FRs towards five hormone nuclear receptors (NRs) associated with reproductive outcomes (estrogen, androgen, glucocorticoid, progesterone, and aryl hydrocarbon receptors) were compiled and organized into tables. Findings were complemented with information from structure-based in silico model predictions and in vivo information when relevant. Results: For the majority of the 52 replacement FRs, experimental in vitro data on activities towards these five NRs were either incomplete (15 FRs) or not found (24 FRs). Within the replacement FRs for which effect data were found, some appeared as candidate EDCs, such as triphenyl phosphate (TPhP) and tris(1,3-dichloropropyl) phosphate (TDCIPP). The search also revealed shared ED profiles. For example, anti-androgenic activity was reported for 19 FRs and predicted for another 21 FRs. Discussion: This comprehensive review points to critical gaps in knowledge on ED potential for many replacement FRs, including chemicals to which the general population is likely exposed. Although this review does not cover all possible characteristics of ED, it allowed the identification of potential EDCs associated with reproductive outcomes, calling for deeper evaluation and possibly future regulation of these chemicals. By identifying shared ED profiles, this work also raises concerns for mixture effects since the population is co-exposed to several FRs and other chemicals., European Commission 733032 859891 857560, Ministry of Education, Youth & Sports - Czech Republic LM2018121 CZ02.1.01/0.0/0.0/18_046/0015975

Published
2021
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6. Regulatory identification of BPA as an endocrine disruptor : Context and methodology

Author

Claude Emond, Jean-Philippe Antignac, Christophe Minier, Jean-Nicolas Ormsby, Sakina Mhaouty-Kodja, Martine Kolf-Clauw, Claire Beausoleil, Lauranne Verines-Jouin, Florence Eustache, René Habert, Cécile Chevrier, Jean-Pierre Cravedi, François Pouzaud, Luc P. Belzunces, Catherine Viguié, Christophe Rousselle, Henri Schroeder, Brigitte Le Magueresse-Battistoni, Marie-Chantal Canivenc-Lavier, Martine Applanat, Patrick Thonneau, Cécile Michel, Luc Multigner, Nicolas Chevalier, Brice M. R. Appenzeller, Rémy Beaudouin, Elodie Pasquier, Elisabeth Elefant, Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Département de Santé Environnementale et Santé au Travail ((DSEST)), École de santé publique, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Centre National de la Recherche Scientifique (CNRS), Luxembourg Institute of Health (LIH), Institut National de l'Environnement Industriel et des Risques (INERIS), Laboratoire de Toxicologie Environnementale (LTE), Institut National de la Recherche Agronomique (INRA), Abeilles et Environnement (AE), Institut National de la Recherche Agronomique (INRA)-Avignon Université (AU), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Stabilité génétique, Cellules Souches et Radiations (SCSR (U_967)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), ANEXPLO, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Composés Alimentaires : Biofonctionnalités et risques Neurotoxiques (CALBINOTOX), Université de Lorraine (UL), Institut National de la Santé et de la Recherche Médicale (INSERM), ANSES, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Human Biomonitoring Research Unit, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Référence sur les Agents Tératogènes, Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Cellules Souches et Radiations (SCSR (U967 / UMR-E_008)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Sud - Paris 11 (UP11), ANEXPLO / CREFRE, Aventis-Institut National de la Santé et de la Recherche Médicale (INSERM)-SANOFI Recherche-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence sur les Agents Tératogènes [CHU Trousseau] (CRAT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Pasquier, Elodie, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE)

Subjects
0301 basic medicine, endocrine system, Brain development, pertubateur endocrinien, Endocrine disruption, Context (language use), Computational biology, MESH: Social Control, Formal, 010501 environmental sciences, Biology, Endocrine Disruptors, 01 natural sciences, Biochemistry, Mammary gland development, bisphenol A, endocrine disruption, ED, SVHC, substance of very high concern, REACh, 03 medical and health sciences, Endocrinology, Bisphenol A, MESH: Phenols, Phenols, Substance of very high concern, MESH: Benzhydryl Compounds, Food and Nutrition, bisphénol a, Animals, Humans, Benzhydryl Compounds, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Endocrinology and metabolism, urogenital system, substance toxique, 3. Good health, Social Control, Formal, MESH: Endocrine Disruptors, 030104 developmental biology, Endocrine disruptor, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Alimentation et Nutrition, Endocrinologie et métabolisme, REACH, Identification (biology)
Abstract

International audience; BPA is one of the most investigated substances for its endocrine disruptor (ED) properties and it is at the same time in the center of many ED-related controversies, the analysis on how BPA fits to the regulatory identification as an ED is a challenge in terms of methodology. It is also a great opportunity to test the regulatory framework with a uniquely data-rich substance and learn valuable lessons for future cases. From this extensive database, it was considered important to engage in a detailed analysis so as to provide specific and strong evidences of ED while reflecting accurately the complexity of the response as well the multiplicity of adverse effects. An appropriate delineation of the scope of the analysis was therefore critical. Four effects namely, alterations of estrous cyclicity, mammary gland development, brain development and memory function, and metabolism, were considered to provide solid evidence of ED-mediated effects of BPA.

Published
2018
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7. Transgenic (cyp19a1b-GFP) zebrafish embryos as a tool for assessing combined effects of oestrogenic chemicals

Author

Stefan Scholz, Knut Erik Tollefsen, François Brion, Eva Fetter, Olivier Kah, Karina Petersen, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de l'Environnement Industriel et des Risques (INERIS), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
MESH: Vitellogenins, tg(cyp19a1b-GFP) zebrafish, Health, Toxicology and Mutagenesis, Endocrine Disruptors, 010501 environmental sciences, MESH: Estrogens, MESH: Regression Analysis, 01 natural sciences, Green fluorescent protein, Animals, Genetically Modified, MESH: Hepatocytes, Vitellogenins, chemistry.chemical_compound, Oestrogen, Mixture, Bioassay, MESH: Animals, Aromatase, Zebrafish, 0303 health sciences, Concentration addition, Independent action, MESH: Endocrine Disruptors, MESH: Oncorhynchus mykiss, Biochemistry, Oncorhynchus mykiss, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Regression Analysis, medicine.medical_specialty, Green Fluorescent Proteins, MESH: Zebrafish Proteins, Estrone, Aquatic Science, Biology, MESH: Animals, Genetically Modified, 03 medical and health sciences, Vitellogenin, MESH: Green Fluorescent Proteins, In vivo, Internal medicine, Toxicity Tests, medicine, Animals, MESH: Aromatase, Potency, MESH: Zebrafish, MESH: Toxicity Tests, 030304 developmental biology, 0105 earth and related environmental sciences, Danio rerio, Estrogens, Zebrafish Proteins, In vitro, Endocrinology, chemistry, Hepatocytes, biology.protein, Rainbow trout hepatocytes
Abstract

International audience; Endocrine disrupting chemicals and especially oestrogen receptor (ER) agonists have been extensively studied over the years due to their potential effects on sexual development and reproduction in vertebrates, notably fish. As ER agonists can exist as complex mixtures in the aquatic environment, evaluating the impact of combined exposure on oestrogenic effects has become increasingly important. Use of predictive models such as concentration addition (CA) and independent action (IA) has allowed assessment of combined estrogenic effects of complex multi-compound mixtures of ER agonists in various fish in vitro and in vivo experimental models. The present work makes use of a transgenic zebrafish strain, tg(cyp19a1b-GFP), which expresses the green fluorescent protein (GFP) under the control of the cyp19a1b (brain aromatase or aromatase B) gene to determine the oestrogenic potency of ER agonists alone or in mixtures. In these studies, tg(cyp19a1b-GFP) zebrafish embryos were exposed for four days (from one to five days post fertilization) to five different oestrogenic chemicals; 17α-ethinylestradiol (EE2), 17β-estradiol (E2), estrone (E1), bisphenol A (BPA) and 4-tert-octylphenol (OP), and three mixtures of up to four of these compounds. The mixture of BPA, OP and E2 was also tested with primary cultures of rainbow trout hepatocytes by analysing the ER-mediated induction of the oestrogenic biomarker vitellogenin in order to compare the performance of the two methods for assessing oestrogenic effects of complex mixtures. The three tested mixtures were predominantly acting in an additive manner on the expression of GFP. Additivity was indicated by the overlap of the 95% confidence interval of the concentration response curves for the observed data with the CA and IA prediction models, and model deviation ratios within a factor of two for a majority of the mixture concentrations. However, minor deviations determined as more than additive effects for the mixture of EE2, E1 and E2 and less than additive effects for the mixture of BPA, OP, EE2 and E1 were observed at the higher mixture concentrations tested. The successful prediction of additivity by CA and IA in tg(cyp19a1b-GFP) zebrafish embryos and deviations at high mixture concentrations seemed to correspond well to results obtained in the rainbow trout hepatocyte assay. The present results clearly show the usefulness of combining predictive modelling and use of in vitro bioassays for rapid screening of oestrogenic effects of complex mixtures and environmental samples.

Published
2013
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8. Phthalate pregnancy exposure and male offspring growth from the intra-uterine period to five years of age

Author

Antonia M. Calafat, Rémy Slama, Sophie Carles, Marie-Aline Charles, Claire Philippat, Jérémie Botton, Pharmaco-épidémiologie des produits de santé et sécurité sanitaire [Site de Saint Denis] (GIS EPIPHARE - ANSM), Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Martel, Anne-Sophie, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Male, Epidemiology, [SDV]Life Sciences [q-bio], Physiology, Fetal growth, 010501 environmental sciences, Endocrine Disruptors, 01 natural sciences, Biochemistry, Body Mass Index, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, MESH: Pregnancy, Child Development, Phthalates, Pregnancy, Medicine, 030212 general & internal medicine, Femur, MESH: Maternal Exposure, MESH: Cohort Studies, General Environmental Science, 2. Zero hunger, Infant growth, MESH: Molecular Weight, MESH: Infant, Newborn, Phthalate, MESH: Ultrasonography, Prenatal, MESH: Infant, MESH: Endocrine Disruptors, [SDV] Life Sciences [q-bio], MESH: Femur, Fetal Weight, Maternal Exposure, Child, Preschool, Prenatal Exposure Delayed Effects, Cohort, Gestation, Female, medicine.medical_specialty, Offspring, Phthalic Acids, Article, Ultrasonography, Prenatal, MESH: Body Mass Index, MESH: Prenatal Exposure Delayed Effects, 03 medical and health sciences, Internal medicine, Humans, 0105 earth and related environmental sciences, MESH: Child Development, Fetus, MESH: Humans, business.industry, MESH: Child, Preschool, Infant, Newborn, Repeated measures design, Infant, MESH: Phthalic Acids, medicine.disease, MESH: Male, Molecular Weight, MESH: Fetal Weight, Endocrinology, chemistry, business, Body mass index, MESH: Female
Abstract

Objective To study associations between prenatal exposure to phthalates and fetal and postnatal growth up to age 5 years in male offspring. Methods Eleven phthalate metabolites were quantified in spot maternal urine samples collected during gestation among 520 women of the EDEN mother-child cohort who gave birth to a boy. Fetal growth was assessed from repeated ultrasound measurements and measurements at birth. We used repeated measures of weight and height in the first 5 years of life to model individual postnatal growth trajectories. We estimated adjusted variations in pre and postnatal growth parameters associated with an interquartile range increase in ln-transformed phthalate metabolite concentrations. Results Monocarboxyisononyl phthalate (MCNP) was positively associated with femoral length during gestation and length at birth. High molecular weight phthalate metabolites were negatively associated with estimated fetal weight throughout pregnancy. Monoethyl phthalate (MEP) showed positive association with weight growth velocity from two to five years and with body mass index at five years (β=0.17 kg/m2, 95% confidence interval, 0.04, 0.30). Conclusions We highlighted associations between gestational exposure to some phthalates and growth in boys. The positive association between MEP and postnatal growth in boys was also reported in several previous human studies.

Published
2016
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9. Selective Activation of Zebrafish Estrogen Receptor Subtypes by Chemicals by Using Stable Reporter Gene Assay Developed in a Zebrafish Liver Cell Line

Author

Patrick Balaguer, Jean-Marc Porcher, Selim Ait-Aissa, François Brion, Farzad Pakdel, Emmanuelle Maillot-Marechal, Anne Cosnefroy, Institut National de l'Environnement Industriel et des Risques (INERIS), Interactions cellulaires et moléculaires (ICM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)

Subjects
ZFL cells, Estrogen receptor, Endocrine Disruptors, 010501 environmental sciences, Ligands, Toxicology, MESH: Estrogens, 01 natural sciences, MESH: Dose-Response Relationship, Drug, in vitro screening assay, Genes, Reporter, MESH: Ligands, MESH: Animals, Luciferases, Promoter Regions, Genetic, MESH: Estrogen Receptor alpha, Zebrafish, MESH: Estrogen Receptor beta, 0303 health sciences, Estradiol, Liver cell, MESH: Gene Expression Regulation, MESH: Endocrine Disruptors, Liver, Receptors, Estrogen, [SDV.TOX]Life Sciences [q-bio]/Toxicology, zebrafish estrogen receptor subtypes, MESH: Receptors, Estrogen, MESH: Estradiol, Signal transduction, MESH: Zebrafish Proteins, Biology, Animal Testing Alternatives, Transfection, MESH: Animal Testing Alternatives, Cell Line, 03 medical and health sciences, MESH: Cell Proliferation, MESH: Promoter Regions, Genetic, Toxicity Tests, Animals, Estrogen Receptor beta, Luciferase, MESH: Toxicity Tests, MESH: Zebrafish, Cell Proliferation, 030304 developmental biology, 0105 earth and related environmental sciences, Reporter gene, Dose-Response Relationship, Drug, Cell growth, MESH: Transfection, MESH: Genes, Reporter, Estrogen Receptor alpha, Estrogens, Zebrafish Proteins, biology.organism_classification, Molecular biology, MESH: Cell Line, Gene Expression Regulation, Cell culture, MESH: Luciferases, MESH: Liver
Abstract

International audience; The number of environmental chemical contaminants suspected to act as endocrine disruptor compounds by interacting with estrogen receptor (ER) signaling pathway has been continuously increasing. To study such interaction, the use of stable reporter gene assays is relevant, but species-specific in vitro screening assays are still lacking to address hazard assessment of estrogenic chemicals in aquatic vertebrates. Here, we describe the development of stable reporter gene assays based on stable expression of subtypes of zebrafish ER (zfERα, zfERβ1, and zfERβ2) coupled to estrogen response element-driven luciferase in a zebrafish liver (ZFL) cell line. The three established cell models, named ZELH-zfERα, ZELH-zfERβ1, and ZELH-zfERβ2, expressed stable and significant basal luciferase signal, which was induced by 17β-estradiol (E2) in a sensitive and dose-response manner at EC(50)s of 0.2, 0.03, and 0.05 nM, respectively. In addition, E2 significantly altered cell proliferation in ZELH-zfERα and ZELH-zfERβ2 cells, but not in parental ZFL and ZELH-zfERβ1 cells, suggesting a functionality of these two receptors to modulate endogenous gene expression in the transfected clones. The screening of various xenoestrogens from different classes in the three models resulted in different luciferase response patterns. Natural and synthetic estrogens and 1,1,1-trichloro-2-(2 chlorophenyl)-2-(4-chlorophenyl)ethane were active at lower concentrations in ZELH-zfERβ1 and ZELH-zfERβ2 than in ZELH-zfERα cells, whereas genistein and zearalenone metabolites as well as three benzophenone derivatives preferentially activated zfERα. Altogether, the newly established models provide specific and convenient in vitro tool for comparative assessment of zfERs selective activation by chemicals within ZFL cell context.

Published
2011
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10. Profiling of benzophenone derivatives using fish and human estrogen receptor-specific in vitro bioassays

Author

José-Manuel Molina-Molina, Vincent Cavaillès, Patrick Balaguer, Elena Gomez, Nicolás Olea, Selim Ait-Aissa, Arnaud Pillon, Aurélie Escande, Farzad Pakdel, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratory of Medical Investigations, Universidad de Granada = University of Granada (UGR)-San Cecilio University Hospital, Hydrosciences Montpellier (HSM), Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Interactions cellulaires et moléculaires (ICM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut National de l'Environnement Industriel et des Risques (INERIS), This research was supported by grants from the European Union Commission (EDEN QLK4-CT-2002-00603 and CASCADE FOOD-CT-2004-506319) and from the French Ministry of Ecology and Sustainable Development (PRG189-07-DRC01) to SA., Le Ster, Yves, CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), University of Granada [Granada]-San Cecilio University Hospital, Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Vitellogenins, Estrogen receptor, Estrogenic activity, Endocrine Disruptors, 010501 environmental sciences, Toxicology, 01 natural sciences, MESH: Dose-Response Relationship, Drug, Vitellogenins, MESH: Animals, Receptor, MESH: Estrogen Receptor alpha, Benzophenones (BPs), MESH: Estrogen Receptor beta, 0303 health sciences, Estradiol, Human androgen receptor (hAR), Rainbow trout estrogen receptor alpha (rtERΑ), Biological activity, Vitellogenin (Vtg), MESH: Endocrine Disruptors, 3. Good health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Reporter gene assay, Cell proliferation assay, MESH: Androgen Antagonists, MESH: Oncorhynchus mykiss, Endocrine disruptor, Oncorhynchus mykiss, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Biological Assay, MESH: Estradiol, Receptor binding assay, medicine.medical_specialty, MESH: Benzophenones, Biology, MESH: Biological Assay, Benzophenones, 03 medical and health sciences, Vitellogenin, MESH: Cell Proliferation, Internal medicine, medicine, Animals, Estrogen Receptor beta, Humans, Cell Proliferation, 030304 developmental biology, 0105 earth and related environmental sciences, Pharmacology, Reporter gene, MESH: Humans, Dose-Response Relationship, Drug, Estrogen Receptor alpha, Androgen Antagonists, Molecular biology, Androgen receptor, Endocrinology, biology.protein, Estrogen receptor alpha, Human estrogen receptor alpha and beta (hERα and hERβ)
Abstract

International audience; Benzophenone (BP) derivatives, BP1 (2,4-dihydroxybenzophenone), BP2 (2,2',4,4'-tetrahydroxybenzophenone), BP3 (2-hydroxy-4-methoxybenzophenone), and THB (2,4,4'-trihydroxybenzophenone) are UV-absorbing chemicals widely used in pharmaceutical, cosmetics, and industrial applications, such as topical sunscreens in lotions and hair sprays to protect skin and hair from UV irradiation. Studies on their endocrine disrupting properties have mostly focused on their interaction with human estrogen receptor alpha (hERalpha), and there has been no comprehensive analysis of their potency in a system allowing comparison between hERalpha and hERbeta activities. The objective of this study was to provide a comprehensive ER activation profile of BP derivatives using ER from human and fish origin in a battery of in vitro tests, i.e., competitive binding, reporter gene based assays, vitellogenin (Vtg) induction in isolated rainbow trout hepatocytes, and proliferation based assays. The ability to induce human androgen receptor (hAR)-mediated reporter gene expression was also examined. All BP derivatives tested except BP3 were full hERalpha and hERbeta agonists (BP2>THB>BP1) and displayed a stronger activation of hERbeta compared with hERalpha, the opposite effect to that of estradiol (E2). Unlike E2, BPs were more active in rainbow trout ERalpha (rtERalpha) than in hERalpha assay. All four BP derivatives showed anti-androgenic activity (THB>BP2>BP1>BP3). Overall, the observed anti-androgenic potencies of BP derivatives, together with their proposed greater effect on ERbeta versus ERalpha activation, support further investigation of their role as endocrine disrupters in humans and wildlife.

Published
2008
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11. Neuroendocrine Disruption: The Emerging Concept

Author

Jean-Pierre Bourguignon, Vance L. Trudeau, Olivier Kah, Centre for Advanced Research in Environmental Genomics, University of Ottawa [Ottawa], Interactions cellulaires et moléculaires (ICM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)

Subjects
History, Health, Toxicology and Mutagenesis, MESH: Environmental Exposure, education, Endocrine Disruptors, 010501 environmental sciences, MESH: Reproduction, Toxicology, 01 natural sciences, 03 medical and health sciences, Animals, Humans, Endocrine system, MESH: Animals, ComputingMilieux_MISCELLANEOUS, reproductive and urinary physiology, health care economics and organizations, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, MESH: Humans, Reproduction, Environmental ethics, Environmental Exposure, Neurosecretory Systems, MESH: Endocrine Disruptors, MESH: Environmental Pollutants, MESH: Neurosecretory Systems, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Environmental Pollutants
Abstract

On July 10, 2010, the beautiful City of Rouen (France) hosted what we believe was the First International Symposium on the “Neuroendocrine Effects of Endocrine Disruptors (NEED).” Several laborator...

Published
2011
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12. Effect of temperature on the release of intentionally and non-intentionally added substances from polyethylene terephthalate (PET) bottles into water: chemical analysis and potential toxicity

Author

Cristina Bach, Isabelle Severin, Serge Etienne, Marie-Christine Chagnon, Xavier Dauchy, Jean-François Munoz, Laboratoire d'hydrologie de Nancy (LHN), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Physiologie de la Nutrition et Toxicologie (NUTox) (U866, Lipides et nutrition, équipe 7) (NUTox), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), ANSES, and Institute Jean Lamour

Subjects
Salmonella typhimurium, MESH: Polyethylene Terephthalates, Endocrine disruption, Formaldehyde, By-products, Gene Expression, 010501 environmental sciences, Endocrine Disruptors, medicine.disease_cause, 01 natural sciences, Analytical Chemistry, Cell Line, chemistry.chemical_compound, 0404 agricultural biotechnology, Polyethylene terephthalate, medicine, Bioassay, Humans, Chemical mixtures, 0105 earth and related environmental sciences, Chromatography, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Mutagenicity Tests, Polyethylene Terephthalates, Drinking Water, Acetaldehyde, Temperature, 04 agricultural and veterinary sciences, General Medicine, Bottled water, biology.organism_classification, 040401 food science, 3. Good health, MESH: Endocrine Disruptors, Cyto-genotoxicity, MESH: Water Pollutants, Chemical, chemistry, 13. Climate action, Environmental chemistry, Micronucleus, PET-bottled water, MESH: Drinking Water, Plastics, Genotoxicity, Bacteria, Water Pollutants, Chemical, Food Science
Abstract

International audience; The purpose of this study was to investigate the impact of temperature on the release of PET-bottle constituents into water and to assess the potential health hazard using in vitro bioassays with bacteria and human cell lines. Aldehydes, trace metals and other compounds found in plastic packaging were analysed in PET-bottled water stored at different temperatures: 40, 50, and 60 °C. In this study, temperature and the presence of CO2 increased the release of formaldehyde, acetaldehyde and antimony (Sb). In parallel, genotoxicity assays (Ames and micronucleus assays) and transcriptional-reporter gene assays for estrogenic and anti-androgenic activity were performed on bottled water extracts at relevant consumer exposure levels. As expected, and in accordance with the chemical formulations specified for PET bottles, neither phthalates nor UV stabilisers were present in the water extracts. However, 2,4-di-tert-butylphenol, a degradation compound of phenolic antioxidants, was detected. In addition, an intermediary monomer, bis(2-hydroxyethyl)terephthalate, was found but only in PET-bottled waters. None of the compounds are on the positive list of EU Regulation No. 10/2011. However, the PET-bottled water extracts did not induce any cytotoxic, genotoxic or endocrine-disruption activity in the bioassays after exposure.

Published
2012
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13. Low concentrations of bisphenol A induce lipid accumulation mediated by the production of reactive oxygen species in the mitochondria of HepG2 cells

Author

Laurence Huc, Anthony Lemarié, Françoise Guéraud, Cécile Héliès-Toussaint, Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), and Huc-Lemarié, Laurence

Subjects
[SDV]Life Sciences [q-bio], 010501 environmental sciences, Mitochondrion, Endocrine Disruptors, Toxicology, 01 natural sciences, MESH: Lipid Peroxidation, chemistry.chemical_compound, MESH: Phenols, MESH: Membrane Potential, Mitochondrial, MESH: Lipid Metabolism, chemistry.chemical_classification, Membrane Potential, Mitochondrial, 0303 health sciences, MESH: Reactive Oxygen Species, General Medicine, Hep G2 Cells, Mitochondria, MESH: Endocrine Disruptors, Biochemistry, Tumor necrosis factor alpha, medicine.symptom, endocrine system, MESH: Mitochondria, Inflammation, MESH: Hep G2 Cells, Biology, Nitric Oxide, 03 medical and health sciences, Phenols, medicine, MESH: Benzhydryl Compounds, Humans, Benzhydryl Compounds, 030304 developmental biology, 0105 earth and related environmental sciences, Reactive oxygen species, Aldehydes, MESH: Humans, Tumor Necrosis Factor-alpha, urogenital system, Interleukin-8, Lipid metabolism, Glutathione, medicine.disease, Lipid Metabolism, MESH: Interleukin-8, chemistry, MESH: Nitric Oxide, MESH: Tumor Necrosis Factor-alpha, Hepatic stellate cell, MESH: Aldehydes, Lipid Peroxidation, Steatosis, Reactive Oxygen Species
Abstract

International audience; Bisphenol A (BPA) is an endocrine-disrupting chemical that leaches from polycarbonate plastics that consequently leads to low-dose human exposure. In addition to its known xenoendocrine action, BPA exerts a wide variety of metabolic effects, but no data are available on its actions on the functions of liver mitochondrial. To assess these effects, HepG2 cells were exposed to BPA (10(-4)-10(-12)M) and physiological parameters were measured by flow cytometry. We demonstrated a significant mitochondrial dysfunction including ROS production, ΔΨ(M) hyperpolarization, lipid accumulation, lipoperoxidation and the release of pro-inflammatory cytokines. In conclusion, we showed that low concentrations of BPA promote lipid accumulation in hepatic cells triggered by disturbances in mitochondrial function, alterations in lipid metabolism and by inflammation that can therefore contribute to steatosis.

Published
2012
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14. Estrogenic and anti-estrogenic activity of 23 commercial textile dyes

Author

Wissem Mnif, Yosra Haj Hamouda, Ahgleb Bartegi, Aziza Ibn Hadj Hassine, Ingrid Bazin, Miguel López-Ferber, Michel De Waard, Catherine Gonzalez, Canepari, Marco, Laboratoire de Génie de l'Environnement Industriel (LGEI), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Laboratory of Biochemistry, Institute of Biotechnology, Department of Biology, King Faisal University (KFU), INSERM U836, équipe 3, Canaux calciques, fonctions et pathologies, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), and LabEX ICST

Subjects
Textile, Anti estrogenic, Health, Toxicology and Mutagenesis, 02 engineering and technology, 010501 environmental sciences, Endocrine Disruptors, Wastewater, MESH: Estrogens, 01 natural sciences, Genes, Reporter, Yeasts, Bioassay, industrial textile effluent, Coloring Agents, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Chemistry, MESH: Yeasts, Textiles, Estrogen Antagonists, General Medicine, 021001 nanoscience & nanotechnology, Pollution, 6. Clean water, MESH: Endocrine Disruptors, MESH: Water Pollutants, Chemical, textile dyes, Environmental chemistry, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biological Assay, 0210 nano-technology, MESH: Coloring Agents, MESH: Estrogen Antagonists, MESH: Biological Assay, MESH: Waste Water, Competitive binding, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], estrogenic activity, Effluent, 0105 earth and related environmental sciences, business.industry, MESH: Genes, Reporter, Public Health, Environmental and Occupational Health, Estrogens, Yeast, Tamoxifen, anti-estrogenic activity, 13. Climate action, Benzopurpurine 4B, MESH: Tamoxifen, MESH: Textiles, business, Water Pollutants, Chemical
Abstract

International audience; The presence of dyes in wastewater effluent of textile industry is well documented. In contrast, the endocrine disrupting effects of these dyes and wastewater effluent have been poorly investigated. Herein, we studied twenty-three commercial dyes, usually used in the textile industry, and extracts of blue jean textile wastewater samples were evaluated for their agonistic and antagonistic estrogen activity. Total estrogenic and anti-estrogenic activities were measured using the Yeast Estrogen Screen bioassay (YES) that evaluates estrogen receptor binding-dependent transcriptional and translational activities. The estrogenic potencies of the dyes and wastewater samples were evaluated by dose-response curves and compared to the dose-response curve of 17β-estradiol (E2), the reference compound. The dose-dependent anti-estrogenic activities of the dyes and wastewater samples were normalized to the known antagonistic effect of 4-hydroxytamoxifen (4-OHT) on the induction of the lac Z reporter gene by E2. About half azo textile dyes have anti-estrogenic activity with the most active being Blue HFRL. Most azo dyes however have no or weak estrogenic activity. E2/dye or E2/waste water ER competitive binding assays show activity of Blue HFRL, benzopurpurine 4B, Everzol Navy Blue FBN, direct red 89 BNL 200% and waste water samples indicating a mechanism of action common to E2. Our results indicate that several textile dyes are potential endocrine disrupting agents. The presence of some of these dyes in textile industry wastewater may thus impact the aquatic ecosystem.

Published
2012
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15. Correcting for the influence of sampling conditions on biomarkers of exposure to phenols and phthalates: a 2-step standardization method based on regression residuals

Author

Sylvaine Cordier, Marion Mortamais, Antonia M. Calafat, Cécile Chevrier, Marie-Aline Charles, Christian Brambilla, Xiaoyun Ye, Claire Philippat, Rémy Slama, Manori J. Silva, Claire Petit, Marinus J.C. Eijkemans, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Groupe de Recherche Sur Le Cancer du Poumon : Bases Moléculaires de la Progression Tumorale, Dépistage et Thérapie Génique, Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), French Agency for Environmental and Occupational Health Safety (ANSES), Le Corre, Morgane, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Time Factors, Phthalate esters, Health, Toxicology and Mutagenesis, Endocrine Disruptors, 010501 environmental sciences, Diisodecyl phthalate, 01 natural sciences, MESH: Linear Models, Toxicology, chemistry.chemical_compound, 0302 clinical medicine, MESH: Pregnancy, MESH: Phenols, Pregnancy, Biomonitoring, 030212 general & internal medicine, medicine.diagnostic_test, lcsh:Public aspects of medicine, Sampling (statistics), Environmental exposure, MESH: Urinalysis, MESH: Endocrine Disruptors, MESH: Young Adult, Environmental chemistry, lcsh:Industrial medicine. Industrial hygiene, Biomarker (medicine), Female, MESH: Environmental Monitoring, Environmental Monitoring, Adult, Urinalysis, MESH: Environmental Exposure, Phthalic Acids, lcsh:RC963-969, Young Adult, 03 medical and health sciences, Phenols, Linear regression, medicine, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Endocrine Disruptor, 0105 earth and related environmental sciences, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, Research, MESH: Time Factors, Public Health, Environmental and Occupational Health, MESH: Biological Markers, lcsh:RA1-1270, MESH: Adult, Environmental Exposure, Biomarker, MESH: Phthalic Acids, chemistry, 13. Climate action, Linear Models, Environmental science, Sampling conditions, MESH: Female, Biomarkers, Environmental epidemiology
Abstract

Background Environmental epidemiology and biomonitoring studies typically rely on biological samples to assay the concentration of non-persistent exposure biomarkers. Between-participant variations in sampling conditions of these biological samples constitute a potential source of exposure misclassification. Few studies attempted to correct biomarker levels for this error. We aimed to assess the influence of sampling conditions on concentrations of urinary biomarkers of select phenols and phthalates, two widely-produced families of chemicals, and to standardize biomarker concentrations on sampling conditions. Methods Urine samples were collected between 2002 and 2006 among 287 pregnant women from Eden and Pélagie cohorts, from which phthalates and phenols metabolites levels were assayed. We applied a 2-step standardization method based on regression residuals. First, the influence of sampling conditions (including sampling hour, duration of storage before freezing) and of creatinine levels on biomarker concentrations were characterized using adjusted linear regression models. In the second step, the model estimates were used to remove the variability in biomarker concentrations due to sampling conditions and to standardize concentrations as if all samples had been collected under the same conditions (e.g., same hour of urine collection). Results Sampling hour was associated with concentrations of several exposure biomarkers. After standardization for sampling conditions, median concentrations differed by ‒ 38 % for 2,5-dichlorophenol to +80 % for a metabolite of diisodecyl phthalate. However, at the individual level, standardized biomarker levels were strongly correlated (correlation coefficients above 0.80) with unstandardized measures. Conclusions Sampling conditions, such as sampling hour, should be systematically collected in biomarker-based studies, in particular when the biomarker half-life is short. The 2-step standardization method based on regression residuals that we proposed in order to limit the impact of heterogeneity in sampling conditions could be further tested in studies describing levels of biomarkers or their influence on health.

Published
2012
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16. Reproductive toxicity of di(2-ethylhexyl) phthalate in selenium-supplemented and selenium-deficient rats

Author

Filiz Hincal, Josiane Arnaud, N. Dilara Zeybek, Esin Asan, Pinar Erkekoglu, Belma Giray, Department of Toxicology, Hacettepe University = Hacettepe Üniversitesi-Faculty of Pharmacy, Department of Histology and Embryology, Hacettepe University = Hacettepe Üniversitesi-Faculty of Medicine, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hamant, Sarah

Subjects
LH, MESH: Selenium, Male, MESH: Organ Size, Health, Toxicology and Mutagenesis, Developmental toxicity, MESH: Dietary Supplements, MESH: Rats, Sprague-Dawley, 010501 environmental sciences, Endocrine Disruptors, MESH: Reproduction, Toxicology, 01 natural sciences, Rats, Sprague-Dawley, chemistry.chemical_compound, Phthalates, Selenium deficiency, FSH, MESH: Follicle Stimulating Hormone, Testis, MESH: Animals, Sperm motility, Testosterone, Epididymis, 0303 health sciences, MESH: Sperm Count, Sperm Count, selenium deficiency, MESH: Testis, Reproduction, MESH: Spermatozoa, Phthalate, selenium supplementation, MESH: Sperm Motility, General Medicine, Organ Size, Spermatozoa, MESH: Endocrine Disruptors, 3. Good health, Liver, Data Interpretation, Statistical, Toxicity, Sperm Motility, di(ethylhexyl) phthalate (DEHP), Reproductive toxicity, endocrine system, medicine.medical_specialty, MESH: Rats, MESH: Epididymis, Biology, sperm, 03 medical and health sciences, Selenium, MESH: Luteinizing Hormone, Internal medicine, Diethylhexyl Phthalate, MESH: Diethylhexyl Phthalate, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, 0105 earth and related environmental sciences, Pharmacology, Chemical Health and Safety, Public Health, Environmental and Occupational Health, Luteinizing Hormone, medicine.disease, testicular histopathology, MESH: Male, Rats, Endocrinology, chemistry, testosterone, Dietary Supplements, Follicle Stimulating Hormone, MESH: Data Interpretation, Statistical, Spermatogenesis, MESH: Liver
Abstract

International audience; Phthalates are abundantly produced plasticizers, and di(ethylhexyl) phthalate (DEHP) is the most widely used derivative in various consumer products and medical devices. Animal studies show that DEHP and various other phthalates cause reproductive and developmental toxicity. Although the evidences are limited, it seems reasonable that DEHP may have a potential for similar adverse effects in humans. Such concerns are increasing, particularly for the developing reproductive system of male infants and children. By taking into account the essentiality of selenium (Se) in testicular structure and functions and the high prevalence of inadequate Se intake in various part of the world, this study was designed to investigate the testicular toxicity of DEHP in Se-deficient male rats and to examine the possible preventive effects of Se supplementation on phthalate toxicity. Se deficiency was generated by feeding 3-week-old Sprague-Dawley rats with a ≤0.05 Se mg/kg diet for 5 weeks. Supplementation groups were on a 1 mg Se/kg diet, and DEHP-treated groups received a 1,000 mg/kg dose by gavage during the last 10 days of the feeding period. Testicular histopathology, sperm count and motility, and sperm morphology were examined, and plasma levels of sex hormones were measured. Toxicity and antiandrogenic effects of DEHP were evidenced by disturbed testicular histology and spermatogenesis, diminished testosterone, leutinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and sperm motility. The effects of DEHP were much more pronounced in Se-deficient rats, whereas Se supplementation was found to be protective, reflecting its regulating role in cellular redox equilibrium.

Published
2011
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17. Bisphenol A induces otolith malformations during vertebrate embryogenesis

Author

Yann Gibert, Patrick Balaguer, Jean-Baptiste Fini, Laure Bernard, Daniel Zalko, Sana Sassi-Messai, Monika Andersson-Lendahl, Vincent Laudet, Barbara A. Demeneix, Jean-Pierre Cravedi, BMC, Ed., Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Evolution des régulations endocriniennes (ERE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Xénobiotiques, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratory of Medical Nutrition, Karolinska Institutet [Stockholm]-Department of Biosciences and Nutrition, CNRS, INSERM, ANR (CES, KISMET), MENRT, ARC, CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Unité de Xénobiotiques, Institut National de la Recherche Agronomique (INRA), Laudet, Vincent, École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon)

Subjects
Xenopus, Estrogen receptor, Environmental pollution, MESH: Water Pollutants, 010501 environmental sciences, Endocrine Disruptors, 01 natural sciences, MESH: Phenols, MESH: Ouabain, MESH: Otolithic Membrane, MESH: Embryonic Development, Water Pollutants, MESH: Animals, MESH: Xenopus, Receptor, Ouabain, Zebrafish, lcsh:QH301-705.5, Fulvestrant, [SDV.BDD]Life Sciences [q-bio]/Development Biology, In Situ Hybridization, MESH: Sodium-Potassium-Exchanging ATPase, perturbateur endocrinien, MESH: Environmental Pollution, 0303 health sciences, Receptors, Thyroid Hormone, biology, Estradiol, Biologie du développement, Development Biology, MESH: Endocrine Disruptors, Endocrine disruptor, Receptors, Estrogen, MESH: Receptors, Estrogen, Female, MESH: Estradiol, Sodium-Potassium-Exchanging ATPase, hormones, hormone substitutes, and hormone antagonists, Research Article, medicine.medical_specialty, Thyroid Hormones, endocrine system, medicine.drug_class, Embryonic Development, 03 medical and health sciences, Otolithic Membrane, MESH: In Situ Hybridization, Phenols, MESH: Thyroid Hormones, Internal medicine, Otolith formation, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, MESH: Benzhydryl Compounds, bisphénol a, Animals, MESH: Receptors, Thyroid Hormone, Benzhydryl Compounds, MESH: Zebrafish, 030304 developmental biology, 0105 earth and related environmental sciences, urogenital system, embryogénèse, biology.organism_classification, vertébré, Endocrinology, lcsh:Biology (General), Estrogen, Environmental Pollution, MESH: Female, Developmental Biology
Abstract

Background The plastic monomer and plasticizer bisphenol A (BPA), used for manufacturing polycarbonate plastic and epoxy resins, is produced at over 2.5 million metric tons per year. Concerns have been raised that BPA acts as an endocrine disruptor on both developmental and reproductive processes and a large body of evidence suggests that BPA interferes with estrogen and thyroid hormone signaling. Here, we investigated BPA effects during embryonic development using the zebrafish and Xenopus models. Results We report that BPA exposure leads to severe malformations of the otic vesicle. In zebrafish and in Xenopus embryos, exposure to BPA during the first developmental day resulted in dose-dependent defects in otolith formation. Defects included aggregation, multiplication and occasionally failure to form otoliths. As no effects on otolith development were seen with exposure to micromolar concentrations of thyroid hormone, 17-ß-estradiol or of the estrogen receptor antagonist ICI 182,780 we conclude that the effects of BPA are independent of estrogen receptors or thyroid-hormone receptors. Na+/K+ ATPases are crucial for otolith formation in zebrafish. Pharmacological inhibition of the major Na+/K+ ATPase with ouabain can rescue the BPA-induced otolith phenotype. Conclusions The data suggest that the spectrum of BPA action is wider than previously expected and argue for a systematic survey of the developmental effects of this endocrine disruptor.

Published
2011
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18. Drug residues and endocrine disruptors in drinking water: risk for humans?

Author

Benoit Roig, E. Touraud, Clémence Coetsier, John P. Sumpter, IMT - MINES ALES (IMT - MINES ALES), and Institut Mines-Télécom [Paris] (IMT)

Subjects
Drug, MESH: Drug Residues, Genetic resistance, media_common.quotation_subject, MESH: Environmental Exposure, 02 engineering and technology, 010501 environmental sciences, Endocrine Disruptors, MESH: Risk Assessment, 01 natural sciences, Risk Assessment, Environmental impact, Toxicology, Iodinated contrast media, Human health, Environmental health, Medicine, Endocrine system, Animals, Humans, MESH: Animals, 0105 earth and related environmental sciences, media_common, MESH: Humans, business.industry, European research, Drinking Water, Public Health, Environmental and Occupational Health, Environmental exposure, Environmental Exposure, 021001 nanoscience & nanotechnology, Drug Residues, MESH: Endocrine Disruptors, 3. Good health, MESH: Water Pollutants, Chemical, Human exposure, Pharmaceuticals, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0210 nano-technology, business, MESH: Drinking Water, Human health risk, Water Pollutants, Chemical
Abstract

International audience; The presence of pharmaceuticals and endocrine disruptors in the environment raises many questions about risk to the environment and human health. Environmental exposure has been largely studied, providing to date a realistic picture of the degree of contamination of the environment by pharmaceuticals and hormones. Conversely, little information is available regarding human exposure. NSAIDS, carbamazepine, iodinated contrast media, β-blockers, antibiotics have been detected in drinking water, mostly in the range of ng/L. it is questioned if such concentrations may affect human health. Currently, no consensus among the scientific community exists on what risk, if any, pharmaceuticals and endocrine disruptors pose to human health. Future European research will focus, on one hand, on genotoxic and cytotoxic anti-cancer drugs and, on the other hand, on the induction of genetic resistance by antibiotics. This review does not aim to give a comprehensive overview of human health risk of drug residues and endocrine disruptors in drinking water but rather highlight important topics of discussion.

Published
2010
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19. 17α-Ethinylestradiol and nonylphenol affect the development of forebrain GnRH neurons through an estrogen receptors-dependent pathway

Author

Nathalie Hinfray, Yann Le Page, Mélanie Vosges, Olivier Kah, Jean-Marc Porcher, Edith Chadili, Yves Combarnous, François Brion, Institut National de l'Environnement Industriel et des Risques (INERIS), Interactions cellulaires et moléculaires (ICM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), French Ministry of Ecology and Sustainable Development [189_09 DRC01], French National Research Agency, and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Embryo, Nonmammalian, MESH: Neurons, Estrogen receptor, 010501 environmental sciences, Endocrine Disruptors, Toxicology, Ethinyl Estradiol, 01 natural sciences, MESH: Estrogens, Gonadotropin-Releasing Hormone, chemistry.chemical_compound, MESH: Prosencephalon, MESH: Phenols, MESH: Gonadotropin-Releasing Hormone, MESH: Animals, Receptor, Zebrafish, Fulvestrant, MESH: Ethinyl Estradiol, Neurons, 0303 health sciences, Estradiol, Estrogen Antagonists, MESH: Endocrine Disruptors, Receptors, Estrogen, [SDV.TOX]Life Sciences [q-bio]/Toxicology, MESH: Receptors, Estrogen, Aromatase B (cyp19a1b), MESH: Estradiol, medicine.drug, medicine.medical_specialty, Endocrine disruption, 17α-Ethinylestradiol, Biology, MESH: Estrogen Antagonists, 03 medical and health sciences, Aromatase, Prosencephalon, Phenols, Internal medicine, medicine, Zebrafish (Danio rerio), Endocrine system, MESH: Aromatase, Animals, MESH: Zebrafish, 030304 developmental biology, 0105 earth and related environmental sciences, Antagonist, MESH: Embryo, Nonmammalian, Estrogens, biology.organism_classification, Nonylphenol, Endocrinology, chemistry, Forebrain, Gonadotropin-releasing-hormone (GnRH)
Abstract

International audience; There is growing evidence that neuroendocrine circuits controlling development and reproduction are targeted by EDCs. We have previously demonstrated that low concentrations of 17α-ethinylestradiol (EE2) disrupt the development of forebrain GnRH neurons during zebrafish development. The objectives of the present study were to determine whether the weak estrogenic compound, nonylphenol (NP), could elicit similar effects to EE2 and to what extent the estrogen receptors are involved in mediating these effects. Using immunohistochemistry, we confirmed that EE2 exposure induces an increase in the number of GnRH-ir neurons and we demonstrated that NP is able to produce similar effects in a concentration-dependent manner. The effects of both NP and EE2 were shown to be blocked by the estrogen receptors (ERs) antagonist ICI 182-780, demonstrating the involvement of functional ERs in mediating their effects. Altogether, these results highlight the need to consider neuroendocrine networks as critical endpoints in the field of endocrine disruption.

Published
2010
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20. 17alpha-ethinylestradiol disrupts the ontogeny of the forebrain GnRH system and the expression of brain aromatase during early development of zebrafish

Author

Yann Le Page, Mélanie Vosges, François Brion, Yves Combarnous, Jean-Marc Porcher, Bon Chu Chung, Olivier Kah, Institut National de l'Environnement Industriel et des Risques (INERIS), Interactions cellulaires et moléculaires (ICM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), French Ministry of Ecology and Sustainable Development 189_09 DRC01, French National Research Agency, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-IFR140-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Institut National de l'Environnement Industriel et des Risques ( INERIS ), Interactions cellulaires et moléculaires ( ICM ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Physiologie de la reproduction et des comportements [Nouzilly] ( PRC ), and Institut National de la Recherche Agronomique ( INRA ) -Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique ( CNRS )

Subjects
Time Factors, 17 alpha-Ethinylestradiol (EE2), MESH : Immunohistochemistry, Health, Toxicology and Mutagenesis, MESH: Neurons, Fluorescent Antibody Technique, MESH : Dose-Response Relationship, Drug, Endocrine Disruptors, 010501 environmental sciences, Endoplasmic Reticulum, Ethinyl Estradiol, 01 natural sciences, MESH: Dose-Response Relationship, Drug, Gonadotropin-Releasing Hormone, chemistry.chemical_compound, MESH: Prosencephalon, (Neuro-) endocrine disruption, MESH: Gonadotropin-Releasing Hormone, MESH : Aromatase, MESH: Animals, Aromatase, Zebrafish, MESH: Fluorescent Antibody Technique, MESH: Ethinyl Estradiol, Neurons, Regulation of gene expression, 0303 health sciences, MESH: Statistics, Nonparametric, MESH : Endoplasmic Reticulum, biology, MESH: Gene Expression Regulation, Enzymologic, Immunohistochemistry, Cell biology, MESH: Endocrine Disruptors, medicine.anatomical_structure, Xenoestrogen, Aromatase B (cyp19a1b), Gonadotropin, hormones, hormone substitutes, and hormone antagonists, MESH : Time Factors, medicine.medical_specialty, endocrine system, medicine.drug_class, Central nervous system, Danio, MESH : Ethinyl Estradiol, MESH : Zebrafish, MESH: Zebrafish Proteins, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Aquatic Science, Development, MESH : Neurons, Gene Expression Regulation, Enzymologic, Statistics, Nonparametric, MESH : Gene Expression Regulation, Enzymologic, 03 medical and health sciences, Prosencephalon, MESH : Zebrafish Proteins, MESH: Endoplasmic Reticulum, Internal medicine, medicine, Zebrafish (Danio rerio), Animals, MESH: Aromatase, MESH: Zebrafish, MESH : Statistics, Nonparametric, MESH : Prosencephalon, 030304 developmental biology, 0105 earth and related environmental sciences, Dose-Response Relationship, Drug, MESH: Time Factors, MESH: Immunohistochemistry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Zebrafish Proteins, biology.organism_classification, MESH : Fluorescent Antibody Technique, Endocrinology, MESH : Endocrine Disruptors, chemistry, Forebrain, biology.protein, MESH : Animals, Gonadotropin-releasing-hormone (GnRH), MESH : Gonadotropin-Releasing Hormone
Abstract

International audience; Until now, studies dedicated to the actions of endocrine disrupting chemicals (EDCs) on the reproductive axis have been concerned with their effects at the gonadal level leaving their actions on neuroendocrine circuits controlling reproduction virtually unexplored. In vertebrates, gonadotropin-releasing hormone (GnRH) is the key factor controlling the activity of the reproductive axis. The development and functioning of GnRH neurons are finely tuned by a series of factors, notably sex steroids, making these neurons potential targets of EDCs, notably in aquatic species. By means of immunohistochemistry, we examined the effects of low levels of ethinylestradiol (EE2 0.02 nM, 0.1 nM, 0.5 nM), a potent synthetic estrogen, on early development (at 5, 10, 20, 30 days post-fertilization) of the forebrain GnRH neurons in a model fish species, the zebrafish (Danio rerio). In parallel, the ER-regulated expression of cytochrome P450 aromatase B (AroB) protein, which is encoded by the cyp19a1b gene, was precisely mapped at the brain and pituitary levels in developing control and EE2-exposed zebrafish. We show that EE2 disrupts the ontogeny of GnRH system by inducing an increase in the number of GnRH-ir neurons and GnRH fibers based on their immunoreactivity as well as a decrease in the size of the GnRH-ir soma and a modification of the migration profile of GnRH-ir neurons. Furthermore, we report a spectacular dose and time-dependent induction of AroB expression in radial glial cells of the developing brain further illustrating the extreme sensitivity of AroB to xenoestrogen and the relevance of AroB as biomarker of xenoestrogen effects on the central nervous system. Collectively, these original and relevant observations highlight the sensitivity of GnRH and AroB to a synthetic estrogen during embryogenesis. These data reinforce the need to further study the mechanisms underlying EDC effects on key neuroendocrine circuits involved in reproduction and brain development of vertebrates.

Published
2010
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21. Bioanalytical characterisation of multiple endocrine- and dioxin-like activities in sediments from reference and impacted small rivers

Author

Stéphane Bouchonnet, Nicolas Creusot, Jean-Marc Porcher, Sophie Bourcier, Said Kinani, Patrick Balaguer, Selim Ait-Aissa, Institut National de l'Environnement Industriel et des Risques (INERIS), Département de Chimie de l'École polytechnique (X-DEP-CHIM), École polytechnique (X), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire des mécanismes réactionnels (DCMR), École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), This study was funded by the French Ministry of Ecology and Sustainable Development (Program 189), the 'Agence Française de Sécurité Sanitaire de l'Environnement et du Travail' (AFSSET, RD-2005-02) and by a doctoral fellowship from the ANRT and INERIS (to SK)., and Aït-Aïssa, Selim

Subjects
[SDE] Environmental Sciences, Geologic Sediments, Receptors, Steroid, Bisphenol A, Health, Toxicology and Mutagenesis, 0211 other engineering and technologies, 02 engineering and technology, Endocrine Disruptors, 010501 environmental sciences, Toxicology, SEDIMENT, 01 natural sciences, chemistry.chemical_compound, Bioassay, media_common, MESH: Dioxins, Pregnane, Pregnane X Receptor, General Medicine, Contamination, Pollution, MESH: Endocrine Disruptors, [SDV.TOX] Life Sciences [q-bio]/Toxicology, MESH: Water Pollutants, Chemical, Receptors, Estrogen, Endocrine disruptor, Receptors, Androgen, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Environmental chemistry, [SDE]Environmental Sciences, MESH: Receptors, Androgen, MESH: Receptors, Estrogen, Biological Assay, MESH: Environmental Monitoring, Environmental Monitoring, media_common.quotation_subject, [SDE.MCG]Environmental Sciences/Global Changes, BIOESSAIS IN VITRO, Estrone, Dioxins, MESH: Biological Assay, MESH: Rivers, Rivers, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, 14. Life underwater, 0105 earth and related environmental sciences, 021110 strategic, defence & security studies, Persistent organic pollutant, MESH: Geologic Sediments, COURS D'EAU, Receptors, Aryl Hydrocarbon, chemistry, 13. Climate action, MESH: Receptors, Aryl Hydrocarbon, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Water Pollutants, Chemical, MESH: Receptors, Steroid
Abstract

International audience; A comprehensive evaluation of organic contamination was performed in sediments sampled in two reference and three impacted small streams where endocrine disruptive (ED) effects in fish have been evidenced. The approach combined quantitative chemical analyses of more than 50 ED chemicals (EDCs) and a battery of in vitro bioassays allowing the quantification of receptor-mediated activities, namely estrogen (ER), androgen (AR), dioxin (AhR) and pregnane X (PXR) receptors. At the most impacted sites, chemical analyses showed the presence of natural estrogens, organochlorine pesticides, parabens, polycyclic aromatic hydrocarbons (16 PAHs), bisphenol A and alkylphenols, while synthetic steroids, myco-estrogens and phyto-estrogens were not detected. Determination of toxic-equivalent amounts showed that 28-96% of estrogenic activities in bioassays (0.2-6.3 ng/g 17beta-estradiol equivalents) were explained by 17beta-estradiol and estrone. PAHs were major contributors (20-60%) to the total dioxin-like activities. Interestingly, high PXR and (anti)AR activities were detected; however, the targeted analysed compounds could not explain the measured biological activities. This study highlighted the presence of multiple organic EDCs in French river sediments subjected to mixed diffuse pollution, and argues for the need to further identify AR and PXR active compounds in the aquatic environment.

Published
2010
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22. Monitoring ligand modulation of protein-protein interactions by mass spectrometry: estrogen receptor alpha-SRC1

Author

Renato Zenobi, Sylvia Eiler, Alexis Nazabal, Marc Ruff, Ryan J. Wenzel, Dino Moras, Cédric Bovet, Florence Granger, Department of Analytical Chemistry, Laboratory of Organic Chemistry, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Peney, Maité

Subjects
MESH: Pharmacology, MESH: Protein Structure, Quaternary, Fluorescence spectrometry, Peptide, MESH: Amino Acid Sequence, Endocrine Disruptors, Mass spectrometry, Ligands, 01 natural sciences, Mass Spectrometry, Analytical Chemistry, 03 medical and health sciences, MESH: Protein Structure, Tertiary, Coactivator, MESH: Ligands, MESH: Protein Binding, Humans, Amino Acid Sequence, Protein Structure, Quaternary, MESH: Estrogen Receptor alpha, 030304 developmental biology, chemistry.chemical_classification, MESH: Mass Spectrometry, Pharmacology, 0303 health sciences, MESH: Humans, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Peptides, Ligand binding assay, 010401 analytical chemistry, Estrogen Receptor alpha, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 0104 chemical sciences, MESH: Endocrine Disruptors, Protein Structure, Tertiary, Nuclear receptor coactivator 1, Matrix-assisted laser desorption/ionization, Biochemistry, chemistry, MESH: Dimerization, Peptides, Estrogen receptor alpha, Dimerization, Protein Binding
Abstract

International audience; Many drugs and chemicals exert their biological effect by modulating protein-protein interactions. In vitro approaches to characterize these mechanisms are often based on indirect measurements (e.g., fluorescence). Here, we used mass spectrometry (MS) to directly monitor the effect of small-molecule ligands on the binding of a coactivator peptide (SRC1) by the human estrogen receptor alpha ligand binding domain (hERalpha LBD). Nanoelectrospray mass spectrometry (nanoESI-MS) and high-mass matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) combined with chemical cross-linking were employed to follow these processes. The chemical cross-linking protocol used prior to high-mass MALDI analysis allows detection of intact noncovalent complexes. The binding of intact hERalpha LBD homodimer with two coactivator peptides was detected with nanoESI-MS and high-mass MALDI-MS only in the presence of an agonist ligand. Furthermore, high-mass MALDI-MS revealed an increase of the homodimer abundance after incubating the receptor with a ligand, independent of the ligand character (i.e., agonist, antagonist). The binding characteristics of the compounds tested by MS correlate very well with their biological activity reported by cell-based assays. High-mass MALDI appears to be an efficient and simple tool for directly monitoring ligand regulation mechanisms involved in protein-protein interactions. Furthermore, the combination of both MS methods allows identifying and characterizing endocrine-disrupting compounds or new drug compounds in an efficient way.

Published
2008
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23. Estrogen receptor-ligand complexes measured by chip-based nanoelectrospray mass spectrometry: an approach for the screening of endocrine disruptors

Author

Renato Zenobi, Dino Moras, Marc Ruff, Bertran Gerrits, Cédric Bovet, Sylvia Eiler, Florence Granger, Arno Wortmann, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Zurich, and Zenobi, R

Subjects
Bisphenol A, Spectrometry, Mass, Electrospray Ionization, 1303 Biochemistry, Electrospray ionization, Estrogen receptor, 610 Medicine & health, 10071 Functional Genomics Center Zurich, Plasma protein binding, Endocrine Disruptors, Ligands, 01 natural sciences, Biochemistry, MESH: Spectrometry, Mass, Electrospray Ionization, Article, 03 medical and health sciences, chemistry.chemical_compound, 1312 Molecular Biology, MESH: Ligands, Humans, Nanotechnology, MESH: Protein Binding, Molecular Biology, MESH: Estrogen Receptor alpha, MESH: Nanotechnology, 030304 developmental biology, 0303 health sciences, Chromatography, MESH: Humans, Chemistry, Ligand binding assay, 010401 analytical chemistry, Estrogen Receptor alpha, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Ligand (biochemistry), 0104 chemical sciences, MESH: Endocrine Disruptors, Nuclear receptor, Biophysics, 570 Life sciences, biology, U7 Systems Biology / Functional Genomics, Estrogen receptor alpha, hormones, hormone substitutes, and hormone antagonists, Protein Binding
Abstract

In the present report, a method based on chip-based nanoelectrospray mass spectrometry (nanoESI-MS) is described to detect noncovalent ligand binding to the human estrogen receptor alpha ligand-binding domain (hERalpha LBD). This system represents an important environmental interest, because a wide variety of molecules, known as endocrine disruptors, can bind to the estrogen receptor (ER) and induce adverse health effects in wildlife and humans. Using proper experimental conditions, the nanoESI-MS approach allowed for the detection of specific ligand interactions with hERalpha LBD. The relative gas-phase stability of selected hERalpha LBD-ligand complexes did not mirror the binding affinity in solution, a result that demonstrates the prominent role of hydrophobic contacts for stabilizing ER-ligand complexes in solution. The best approach to evaluate relative solution-binding affinity by nanoESI-MS was to perform competitive binding experiments with 17beta-estradiol (E2) used as a reference ligand. Among the ligands tested, the relative binding affinity for hERalpha LBD measured by nanoESI-MS was 4-hydroxtamoxifen approximately diethylstilbestrol > E2 >> genistein >> bisphenol A, consistent with the order of the binding affinities in solution. The limited reproducibility of the bound to free protein ratio measured by nanoESI-MS for this system only allowed the binding constants (K(d)) to be estimated (low nanomolar range for E2). The specificity of nanoESI-MS combined with its speed (1 min/ligand), low sample consumption (90 pmol protein/ligand), and its sensitivity for ligand (30 ng/mL) demonstrates that this technique is a promising method for screening suspected endocrine disrupting compounds and to qualitatively evaluate their binding affinity.

Published
2007
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24. Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment

Author

Luc P. Belzunces, Christophe Rousselle, Scott M. Belcher, Fabien Lagarde, Claire Beausoleil, Claude Emond, Michel Guerbet, Beausoleil, Claire, Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), University of Cincinnati (UC), Abeilles et Environnement (AE), Institut National de la Recherche Agronomique (INRA)-Avignon Université (AU), BioSimulation Consulting Inc., Aliments Bioprocédés Toxicologie Environnements (ABTE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)

Subjects
xenœstrogène, MESH: Dose response relationship, drug, Health, Toxicology and Mutagenesis, Scoring criteria, Decision tree, Context (language use), Review, 010501 environmental sciences, 01 natural sciences, Toxicology, 03 medical and health sciences, Bisphenol A, Endocrine disruptors, NMDR, Non-monotonic, Dose-reponse, Risk assessment, Endocrine system, bisphénol a, effet dose, MESH: Endocrine disruptors, dose-réponse hormétique, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, Dose-Response Relationship, Drug, Public Health, Environmental and Occupational Health, Environmental Exposure, Environmental exposure, Receptor Desensitization, Dose-response, [SDV.TOX]Life Sciences [q-bio]/Toxicology, glande mammaire, Environmental Pollutants, Psychology, MESH: Risk assessment, Environmental Monitoring, Cognitive psychology, expression des gènes
Abstract

International audience; Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that report NMDR relationships with endocrine disruptors. Fifty-one experimental studies that investigated various effects associated with endocrine disruption elicited by many substances were selected. Scoring criteria were applied by adaptation of an approach previously used for identification of hormesis-type dose-response relationships. Out of the 148 NMDR relationships analyzed, 82 were categorized with this method as having a " moderate " to " high " level of plausibility for various effects. Numerous modes of action described in the literature can explain such phenomena. NMDR can arise from numerous molecular mechanisms such as opposing effects induced by multiple receptors differing by their affinity, receptor desensitization, negative feedback with increasing dose, or dose-dependent metabolism modulation. A stepwise decision tree was developed as a tool to standardize the analysis of NMDR relationships observed in the literature with the final aim to use these results in a Risk Assessment purpose. This decision tree was finally applied to studies focused on the effects of bisphenol A.

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