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1. Cross-cutting studies of per- and polyfluorinated alkyl substances (PFAS) in Arctic wildlife and humans

Author

Lohmann, Rainer, Abass, Khaled, Bonefeld-Jørgensen, Eva Cecilie, Bossi, Rossana, Dietz, Rune, Ferguson, Steve, Fernie, Kim J., Grandjean, Philippe, Herzke, Dorte, Houde, Magali, Lemire, Mélanie, Letcher, Robert J., Muir, Derek, De Silva, Amila O., Ostertag, Sonja K., Rand, Amy A., Søndergaard, Jens, Sonne, Christian, Sunderland, Elsie M., Vorkamp, Katrin, Wilson, Simon, and Weihe, Pal

Published
2024
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13. Attention Deficit/Hyperactivity Disorder and Childhood Autism in Association with Prenatal Exposure to Perfluoroalkyl Substances: A Nested Case–Control Study in the Danish National Birth Cohort

Author

Liew, Zeyan, Ritz, Beate, von Ehrenstein, Ondine S, Bech, Bodil Hammer, Nohr, Ellen Aagaard, Fei, Chunyuan, Bossi, Rossana, Henriksen, Tine Brink, Bonefeld-Jørgensen, Eva Cecilie, and Olsen, Jørn

Subjects
Intellectual and Developmental Disabilities (IDD), Brain Disorders, Clinical Research, Attention Deficit Hyperactivity Disorder (ADHD), Autism, Pediatric, Mental Health, Behavioral and Social Science, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Adult, Alkanesulfonic Acids, Attention Deficit Disorder with Hyperactivity, Autistic Disorder, Caprylates, Case-Control Studies, Child, Cohort Studies, Denmark, Environmental Pollutants, Female, Fluorocarbons, Humans, Male, Maternal Exposure, Pregnancy, Prenatal Exposure Delayed Effects, Environmental Sciences, Medical and Health Sciences, Toxicology
Abstract

BackgroundPerfluoroalkyl substances (PFASs) are persistent pollutants found to be endocrine disruptive and neurotoxic in animals. Positive correlations between PFASs and neurobehavioral problems in children were reported in cross-sectional data, but findings from prospective studies are limited.ObjectivesWe investigated whether prenatal exposure to PFASs is associated with attention deficit/hyperactivity disorder (ADHD) or childhood autism in children.MethodsAmong 83,389 mother-child pairs enrolled in the Danish National Birth Cohort during 1996-2002, we identified 890 ADHD cases and 301 childhood autism cases from the Danish National Hospital Registry and the Danish Psychiatric Central Registry. From this cohort, we randomly selected 220 cases each of ADHD and autism, and we also randomly selected 550 controls frequency matched by child's sex. Sixteen PFASs were measured in maternal plasma collected in early or mid-pregnancy. We calculated risk ratios (RRs) using generalized linear models, taking into account sampling weights.ResultsPerfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs were quantified in ≥ 90% of the samples. We did not find consistent evidence of associations between mother's PFAS plasma levels and ADHD [per natural log nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR = 0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73, 1.31)]. We found positive as well as negative associations between higher PFAS quartiles and ADHD in models that simultaneously adjusted for all PFASs, but these estimates were imprecise.ConclusionsIn this study we found no consistent evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or childhood autism in children.

Published
2015

16. Arctic Monitoring and Assessment Programme (AMAP)—IPY Meeting in Iqaluit, Nunavut, Canada (June 2009), and AMAP Human Health Assessment 2009

Author

Hansen, Jens C., Van Oostdam, Jay, Gilman, Andrew P., Odland, Jon Øyvind, Donaldson, Shawn G., Vaktskjold, Arild, Tikhonov, Constantine, Dudarev, Alexey A., Ayotte, Pierre, Berner, James E., Bonefeld-Jørgensen, Eva Cecilie, Carlsen, Anders, Deutch, Bente, Dewailly, Eric, Furgal, Christopher, Muckle, Gina, Ólafsdóttir, Kristín, Pedersen, Henning Sloth, Rautio, Arja, Sandanger, Torkjel M., Weihe, Pal, Weber, Jean-Phillipe, Savolainen, Markku, Skinner, Kelly, Kallenborn, Roland, Series editor, di Prisco, Guido, Series editor, Walton, David, Series editor, and Barr, Susan, Series editor

Published
2016
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17. Maternal serum dioxin-like activity and gestational age at birth and indices of foetal growth:The Aarhus birth cohort

Author

Long, Manhai, Wielsøe, Maria, Bech, Bodil Hammer, Henriksen, Tine Brink, and Bonefeld-Jørgensen, Eva Cecilie

Subjects
Foetal growth indices, Pregnant women, Gestational age at birth, Persistent organic pollutants, Aryl hydrocarbon receptor
Abstract

Human exposure to lipophilic persistent organic pollutants (lipPOP) is ubiquitous and life-long, beginning during foetal development. Exposure to lipPOP elicits a number of species and tissue specific responses including dioxin-like activity which involve the activation of aryl hydrocarbon receptor (AhR). This study aims i) to describe the combined dioxin-like activity in serum from Danish pregnant women collected during 2011-2013; ii) to assess the association between maternal serum dioxin-like activity, gestational age at birth and foetal growth indices. The serum lipPOP fraction was extracted using Solid Phase Extraction and cleaned-up on Supelco multi-layer silica and florisil columns. The combined dioxin-like activity of the extract was determined using the AhR reporter gene bioassay, expressed as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalent (TEQ) [AhR-TEQ (pg/g lipid)]. The association of AhR-TEQ and foetal growth indices (birth weight, birth length and head circumference) and gestational age was assessed by linear regression models. We detected AhR-TEQ in 93.9 % of maternal first trimester serum samples, with a median level of 185 pg/g lipid. Each ln-unit increase in AhR-TEQ was associated with an increase in birth weight of 36 g (95 % CI: 5; 68), birth length of 0.2 cm (95 % CI: 0.01; 0.3) and pregnancy duration of 1 day (95 % CI: 0; 1.5). In women who never smoked, higher AhR-TEQ values were associated with higher birth weight and longer duration of gestation, while in smokers the association was the opposite. Mediation analyses suggested that gestational age may mediate the association of AhR-TEQ with foetal growth indices. We conclude that AhR activating substances are present in the bloodstream of almost all pregnant women in Denmark and the AhR-TEQ level was around four times higher than previously reported. The AhR-TEQ was associated with slightly longer gestational duration and thereby higher birth weight and birth length.

Published
2023

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

Author

Rodríguez-Carrillo, Andrea, primary, Mustieles, Vicente, additional, Salamanca-Fernández, Elena, additional, Olivas-Martínez, Alicia, additional, Suárez, Beatriz, additional, Bajard, Lola, additional, Baken, Kirsten, additional, Blaha, Ludek, additional, Bonefeld-Jørgensen, Eva Cecilie, additional, Couderq, Stephan, additional, D'Cruz, Shereen Cynthia, additional, Fini, Jean-Baptiste, additional, Govarts, Eva, additional, Gundacker, Claudia, additional, Hernández, Antonio F., additional, Lacasaña, Marina, additional, Laguzzi, Federica, additional, Linderman, Birgitte, additional, Long, Manhai, additional, Louro, Henriqueta, additional, Neophytou, Christiana, additional, Oberemn, Axel, additional, Remy, Sylvie, additional, Rosenmai, Anna Kjerstine, additional, Saber, Anne Thoustrup, additional, Schoeters, Greet, additional, Silva, Maria Joao, additional, Smagulova, Fatima, additional, Uhl, Maria, additional, Vinggaard, Anne Marie, additional, Vogel, Ulla, additional, Wielsøe, Maria, additional, Olea, Nicolás, additional, and Fernández, Mariana F., additional

Published
2023
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19. Implementation of effect biomarkers in human biomonitoring studies:A systematic approach synergizing toxicological and epidemiological knowledge

Author

Rodríguez-Carrillo, Andrea, Mustieles, Vicente, Salamanca-Fernández, Elena, Olivas-Martínez, Alicia, Suárez, Beatriz, Bajard, Lola, Baken, Kirsten, Blaha, Ludek, Bonefeld-Jørgensen, Eva Cecilie, Couderq, Stephan, D'Cruz, Shereen Cynthia, Fini, Jean-Baptiste, Govarts, Eva, Gundacker, Claudia, Hernández, Antonio F., Lacasaña, Marina, Laguzzi, Federica, Linderman, Birgitte, Long, Manhai, Louro, Henriqueta, Neophytou, Christiana, Oberemn, Axel, Remy, Sylvie, Rosenmai, Anna Kjerstine, Saber, Anne Thoustrup, Schoeters, Greet, Silva, Maria Joao, Smagulova, Fatima, Uhl, Maria, Vinggaard, Anne Marie, Vogel, Ulla, Wielsøe, Maria, Olea, Nicolás, Fernández, Mariana F., Rodríguez-Carrillo, Andrea, Mustieles, Vicente, Salamanca-Fernández, Elena, Olivas-Martínez, Alicia, Suárez, Beatriz, Bajard, Lola, Baken, Kirsten, Blaha, Ludek, Bonefeld-Jørgensen, Eva Cecilie, Couderq, Stephan, D'Cruz, Shereen Cynthia, Fini, Jean-Baptiste, Govarts, Eva, Gundacker, Claudia, Hernández, Antonio F., Lacasaña, Marina, Laguzzi, Federica, Linderman, Birgitte, Long, Manhai, Louro, Henriqueta, Neophytou, Christiana, Oberemn, Axel, Remy, Sylvie, Rosenmai, Anna Kjerstine, Saber, Anne Thoustrup, Schoeters, Greet, Silva, Maria Joao, Smagulova, Fatima, Uhl, Maria, Vinggaard, Anne Marie, Vogel, Ulla, Wielsøe, Maria, Olea, Nicolás, and Fernández, Mariana F.

Abstract

Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2′-deoxygua

Published
2023

20. A systematic approach synergizing toxicological and epidemiological knowledge

Author

Rodríguez-Carrillo, Andrea, Mustieles, Vicente, Salamanca-Fernández, Elena, Olivas-Martínez, Alicia, Suárez, Beatriz, Bajard, Lola, Baken, Kirsten, Blaha, Ludek, Bonefeld-Jørgensen, Eva Cecilie, Couderq, Stephan, D'Cruz, Shereen Cynthia, Fini, Jean Baptiste, Govarts, Eva, Gundacker, Claudia, Hernández, Antonio F., Lacasaña, Marina, Laguzzi, Federica, Linderman, Birgitte, Long, Manhai, Louro, Henriqueta, Neophytou, Christiana, Oberemn, Axel, Remy, Sylvie, Rosenmai, Anna Kjerstine, Saber, Anne Thoustrup, Schoeters, Greet, Silva, Maria Joao, Smagulova, Fatima, Uhl, Maria, Vinggaard, Anne Marie, Vogel, Ulla, Wielsøe, Maria, Olea, Nicolás, Fernández, Mariana F., Centre for Toxicogenomics and Human Health (ToxOmics), and NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)

Subjects
HBM4EU, Environmental chemicals, SDG 3 - Good Health and Well-being, Public Health, Environmental and Occupational Health, Human biomonitoring programs, Occupational chemicals, Effect biomarkers, Biomarkers
Abstract

Funding Information: This work was supported by the European Union's Horizon 2020 research and innovation program projects HBM4EU [grant number 733032 ]. Authors acknowledge the editorial assistance of Richard Davies. Publisher Copyright: © 2023 The Author(s) Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2′-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals. publishersversion published

Published
2023

21. Application of AOPs to assist regulatory assessment of chemical risks – Case studies, needs and recommendations

Author

Bajard, Lola, primary, Adamovsky, Ondrej, additional, Audouze, Karine, additional, Baken, Kirsten, additional, Barouki, Robert, additional, Beltman, Joost B., additional, Beronius, Anna, additional, Bonefeld-Jørgensen, Eva Cecilie, additional, Cano-Sancho, German, additional, de Baat, Milo L., additional, Di Tillio, Filippo, additional, Fernández, Mariana F., additional, FitzGerald, Rex E., additional, Gundacker, Claudia, additional, Hernández, Antonio F., additional, Hilscherova, Klara, additional, Karakitsios, Spyros, additional, Kuchovska, Eliska, additional, Long, Manhai, additional, Luijten, Mirjam, additional, Majid, Sanah, additional, Marx-Stoelting, Philip, additional, Mustieles, Vicente, additional, Negi, Chander K., additional, Sarigiannis, Dimosthenis, additional, Scholz, Stefan, additional, Sovadinova, Iva, additional, Stierum, Rob, additional, Tanabe, Shihori, additional, Tollefsen, Knut Erik, additional, van den Brand, Annick D., additional, Vogs, Carolina, additional, Wielsøe, Maria, additional, Wittwehr, Clemens, additional, and Blaha, Ludek, additional

Published
2023
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23. Reduced Birth Weight and Exposure to Per- and Polyfluoroalkyl Substances: A Review of Possible Underlying Mechanisms Using the AOP-HelpFinder

Author

Gundacker, Claudia, primary, Audouze, Karine, additional, Widhalm, Raimund, additional, Granitzer, Sebastian, additional, Forsthuber, Martin, additional, Jornod, Florence, additional, Wielsøe, Maria, additional, Long, Manhai, additional, Halldórsson, Thórhallur Ingi, additional, Uhl, Maria, additional, and Bonefeld-Jørgensen, Eva Cecilie, additional

Published
2022
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27. Arctic Monitoring and Assessment Programme (AMAP)—IPY Meeting in Iqaluit, Nunavut, Canada (June 2009), and AMAP Human Health Assessment 2009

Author

Hansen, Jens C., primary, Van Oostdam, Jay, additional, Gilman, Andrew P., additional, Odland, Jon Øyvind, additional, Donaldson, Shawn G., additional, Vaktskjold, Arild, additional, Tikhonov, Constantine, additional, Dudarev, Alexey A., additional, Ayotte, Pierre, additional, Berner, James E., additional, Bonefeld-Jørgensen, Eva Cecilie, additional, Carlsen, Anders, additional, Deutch, Bente, additional, Dewailly, Eric, additional, Furgal, Christopher, additional, Muckle, Gina, additional, Ólafsdóttir, Kristín, additional, Pedersen, Henning Sloth, additional, Rautio, Arja, additional, Sandanger, Torkjel M., additional, Weihe, Pal, additional, Weber, Jean-Phillipe, additional, Savolainen, Markku, additional, and Skinner, Kelly, additional

Published
2016
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37. Receptor-based in vitro activities to assess human exposure to chemical mixtures and related health impacts

Author

Vinggaard, Anne Marie, Bonefeld-Jørgensen, Eva Cecilie, Jensen, Tina Kold, Fernandez, Mariana F, Rosenmai, Anna Kjerstine, Taxvig, Camilla, Rodriguez-Carrillo, Andrea, Wielsøe, Maria, Long, Manhai, Olea, Nicolas, Antignac, Jean-Philippe, Hamers, Timo, Lamoree, Marja, Vinggaard, Anne Marie, Bonefeld-Jørgensen, Eva Cecilie, Jensen, Tina Kold, Fernandez, Mariana F, Rosenmai, Anna Kjerstine, Taxvig, Camilla, Rodriguez-Carrillo, Andrea, Wielsøe, Maria, Long, Manhai, Olea, Nicolas, Antignac, Jean-Philippe, Hamers, Timo, and Lamoree, Marja

Abstract

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

Published
2021

42. Receptor-based in vitro activities to assess human exposure to chemical mixtures and related health impacts

Author

Vinggaard, Anne Marie, primary, Bonefeld-Jørgensen, Eva Cecilie, additional, Jensen, Tina Kold, additional, Fernandez, Mariana F., additional, Rosenmai, Anna Kjerstine, additional, Taxvig, Camilla, additional, Rodriguez-Carrillo, Andrea, additional, Wielsøe, Maria, additional, Long, Manhai, additional, Olea, Nicolas, additional, Antignac, Jean-Philippe, additional, Hamers, Timo, additional, and Lamoree, Marja, additional

Published
2021
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43. Prenatal exposure to perfluoroalkyl substances and behavioral difficulties in childhood at 7 and 11 years

Author

Luo, Jiajun, primary, Xiao, Jingyuan, additional, Gao, Yu, additional, Ramlau-Hansen, Cecilia Høst, additional, Toft, Gunnar, additional, Li, Jiong, additional, Obel, Carsten, additional, Andersen, Stine Linding, additional, Deziel, Nicole C., additional, Tseng, Wan-Ling, additional, Inoue, Kosuke, additional, Bonefeld-Jørgensen, Eva Cecilie, additional, Olsen, Jørn, additional, and Liew, Zeyan, additional

Published
2020
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46. Perfluoroalkyl Substances and Maternal Thyroid Hormones in Early Pregnancy; Findings in the Danish National Birth Cohort

Author

Inoue, Kosuke, primary, Ritz, Beate, additional, Andersen, Stine Linding, additional, Ramlau-Hansen, Cecilia Høst, additional, Høyer, Birgit Bjerre, additional, Bech, Bodil Hammer, additional, Henriksen, Tine Brink, additional, Bonefeld-Jørgensen, Eva Cecilie, additional, Olsen, Jørn, additional, and Liew, Zeyan, additional

Published
2019
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