Endocrine disrupting chemicals: exposure, effects on human health, mechanism of action, models for testing and strategies for prevention

Yılmaz, Bayram; Terekeci, Hakan; Sandal, Süleyman; Keleştimur, Fahrettin

doi:10.1007/s11154-019-09521-z

Cited by 371 publications

(144 citation statements)

References 209 publications

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“…In this regard, the possible effects of co-exposures to other risk factors on the thyroid function in the workplaces, e.g., chemical, biological and physical factors, should be considered. Although taking into consideration the different conditions of exposures and the remarkable inter-subject variability, the thyroid is very sensitive to the action of chemical disruptors [43]. Therefore, it cannot be ruled out that physicians, e.g., anesthesiologists and surgeons, employees in rubber and ceramic industry, as well as those involved in the packaging units of a pharmaceutical industry, may be exposed to chemicals, e.g., anesthetics, metals and plasticizers that may mediate hormonal alterations as reported in occupational, epidemiological and experimental settings [44][45][46][47][48][49].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Shift-Work and Night Shift-Work on Thyroid: A Systematic Review

Leso

Vetrani

Sicignano

et al. 2020

IJERPH

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Thyroid hormones are regulated by the pituitary thyroid stimulating hormone (TSH), whose secretion presents a circadian rhythmicity. Indeed, it is conceivable that shift- and night shift-work, affecting sleep-wake rhythms, may impact thyroid functionality. Therefore, the aim of the present review was to provide an overview on the association between shift- and night shift-work and thyroid hormonal changes and disease development. A systematic review of studies available in PubMed, Scopus, and ISI Web of Science databases was performed. A positive association between night shift-work and increased TSH concentrations was reported by most of the reviewed investigations. Inconclusive evidence was available on thyroid diseases. However, the limited number of studies, the noticeable heterogeneity in the shift-work scheduling, in terms of amount, duration, type of shift- or night shift-work, prevents easily integrating findings and extrapolating definite conclusions. Further investigation seems necessary to better define the relationship between shift schedules and different thyroid outcomes, and possible long-term implications of early functional changes. Overall, this may support the adoption of advanced risk assessment and management strategies aimed to achieve a safer workplace organization and a timely, responsible realization of all the benefits of a 24-h economy.

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Section: Discussionmentioning

confidence: 99%

The Impact of Shift-Work and Night Shift-Work on Thyroid: A Systematic Review

Leso

Vetrani

Sicignano

et al. 2020

IJERPH

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“…Several groups of pesticides have been linked to deleterious effects on neuroendocrine, reproductive, and immunological functions and dysregulation of energy metabolism [ 3 ]. The use of organochlorinated compounds such as dieldrin or endosulfan have largely been abandoned but both activate CAR and PXR in vitro, and increase expression of their CYP target genes in animals or in human HepaRG cells [ 45 , 46 , 210 , 211 ].…”

Section: Metabolic Effects Of Edc Classes Potentially Mediated By mentioning

confidence: 99%

“…EDCs may interfere with regulation of body homeostasis by mimicking, suppressing, or altering the normal physiological responses. These adverse actions can be mediated by e.g., direct agonism/antagonism of these receptors, indirect effects via modulation of synthesis or clearance of endogenous receptor ligands, interference of the downstream signaling pathways or the endocrine feedback systems between tissues or through epigenetic changes that dysregulate the hormonal signaling pathways and may be transmitted to the next progeny [ 3 ]. Due to the high degree of sequence similarity and conservation of signaling pathways for many receptors across species, EDCs can exert their effects in both wildlife and humans.…”

Section: Introductionmentioning

confidence: 99%

Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR

Küblbeck

Niskanen

Honkakoski

2020

Cells

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During the last two decades, the constitutive androstane receptor (CAR; NR1I3) has emerged as a master activator of drug- and xenobiotic-metabolizing enzymes and transporters that govern the clearance of both exogenous and endogenous small molecules. Recent studies indicate that CAR participates, together with other nuclear receptors (NRs) and transcription factors, in regulation of hepatic glucose and lipid metabolism, hepatocyte communication, proliferation and toxicity, and liver tumor development in rodents. Endocrine-disrupting chemicals (EDCs) constitute a wide range of persistent organic compounds that have been associated with aberrations of hormone-dependent physiological processes. Their adverse health effects include metabolic alterations such as diabetes, obesity, and fatty liver disease in animal models and humans exposed to EDCs. As numerous xenobiotics can activate CAR, its role in EDC-elicited adverse metabolic effects has gained much interest. Here, we review the key features and mechanisms of CAR as a xenobiotic-sensing receptor, species differences and selectivity of CAR ligands, contribution of CAR to regulation hepatic metabolism, and evidence for CAR-dependent EDC action therein.

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“…As described, many EDs have been established as MDCs and, as such, have adverse effects on metabolic health [15][16][17][18][19][20][21]. Suspected MDCs from compound classes that have been shown to interact with metabolism-related NRs, have effects on mitochondrial function, or cause adverse metabolic effects, e.g., by inhibiting key enzyme of glucose utilization, are prime candidates for EDCMET studies (Table 1).…”

Section: Edcmet Approachmentioning

confidence: 99%

“…EDs can interfere with the endocrine system by numerous mechanisms, such as impeding synthesis, secretion, transport, metabolism, binding, or elimination of natural hormones, or by mimicking hormone action at the level of receptor binding and signal transduction [8][9][10][11][12][13] and may influence the regulation of general homeostasis of the body and contribute to the adverse metabolic phenotypes. Indeed, epidemiological data from humans and experimental data from rodents indicate that exposure to certain EDs, the so-called metabolism disrupting chemicals (MDCs), may predispose patients to different components of metabolic syndrome, T2D, and NAFLD (for reviews, see [15][16][17][18][19][20]). The main targets for MDCs are liver and adipose tissue, where they can provoke, e.g., adipogenesis and fat accumulation [21], insulin resistance [22], and changes in cholesterol and bile acid metabolism [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

The EDCMET Project: Metabolic Effects of Endocrine Disruptors

Küblbeck

Vuorio

Niskanen

et al. 2020

IJMS

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Endocrine disruptors (EDs) are defined as chemicals that mimic, block, or interfere with hormones in the body’s endocrine systems and have been associated with a diverse array of health issues. The concept of endocrine disruption has recently been extended to metabolic alterations that may result in diseases, such as obesity, diabetes, and fatty liver disease, and constitute an increasing health concern worldwide. However, while epidemiological and experimental data on the close association of EDs and adverse metabolic effects are mounting, predictive methods and models to evaluate the detailed mechanisms and pathways behind these observed effects are lacking, thus restricting the regulatory risk assessment of EDs. The EDCMET (Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways) project brings together systems toxicologists; experimental biologists with a thorough understanding of the molecular mechanisms of metabolic disease and comprehensive in vitro and in vivo methodological skills; and, ultimately, epidemiologists linking environmental exposure to adverse metabolic outcomes. During its 5-year journey, EDCMET aims to identify novel ED mechanisms of action, to generate (pre)validated test methods to assess the metabolic effects of Eds, and to predict emergent adverse biological phenotypes by following the adverse outcome pathway (AOP) paradigm.

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Endocrine disrupting chemicals: exposure, effects on human health, mechanism of action, models for testing and strategies for prevention

Cited by 371 publications

References 209 publications

The Impact of Shift-Work and Night Shift-Work on Thyroid: A Systematic Review

The Impact of Shift-Work and Night Shift-Work on Thyroid: A Systematic Review

Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR

The EDCMET Project: Metabolic Effects of Endocrine Disruptors

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