scholarly journals Developmental exposure to the DE-71 mixture of polybrominated diphenyl ether (PBDE) flame retardants induce a complex pattern of endocrine disrupting effects in rats

PeerJ ◽  
2022 ◽  
Vol 10 ◽  
pp. e12738
Author(s):  
Louise Ramhøj ◽  
Karen Mandrup ◽  
Ulla Hass ◽  
Terje Svingen ◽  
Marta Axelstad
Keyword(s):  
Mammary Gland ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Developmental Stages ◽  
Developmental Toxicity ◽  
Diphenyl Ether ◽  
Male Offspring ◽  
Developmental Exposure ◽  
Endocrine Disrupting

Polybrominated diphenyl ethers (PBDEs) are legacy compounds with continued widespread human exposure. Despite this, developmental toxicity studies of DE-71, a mixture of PBDEs, are scarce and its potential for endocrine disrupting effects in vivo is not well covered. To address this knowledge gap, we carried out a developmental exposure study with DE-71. Pregnant Wistar rat dams were exposed to 0, 40 or 60 mg/kg bodyweight/day from gestation day 7 to postnatal day 16, and both sexes were examined. Developmental exposure affected a range of reproductive toxicity endpoints. Effects were seen for both male and female anogenital distances (AGD), with exposed offspring of either sex displaying around 10% shorter AGD compared to controls. Both absolute and relative prostate weights were markedly reduced in exposed male offspring, with about 40% relative to controls. DE-71 reduced mammary gland outgrowth, especially in male offspring. These developmental in vivo effects suggest a complex effect pattern involving anti-androgenic, anti-estrogenic and maybe estrogenic mechanisms depending on tissues and developmental stages. Irrespective of the specific underlying mechanisms, these in vivo results corroborate that DE-71 causes endocrine disrupting effects and raises concern for the effects of PBDE-exposure on human reproductive health, including any potential long-term consequences of disrupted mammary gland development.

Developing a Laboratory Animal Model for Perinatal Endocrine Disruption: The Hamster Chronicles

2002 ◽  
Vol 227 (9) ◽  
pp. 709-723 ◽  
Author(s):  
William J. Hendry ◽  
Daniel M. Sheehan ◽  
Shafiq A. Khan ◽  
Jeffrey V. May
Keyword(s):  
Endocrine Disruption ◽  
Reproductive Tract ◽  
Developmental Toxicity ◽  
Endocrine Disrupting Chemicals ◽  
Experimental System ◽  
Endocrine Disrupting ◽  
Considerable Concern ◽  
Insight Into ◽  
Future Plans

At the biomedical, regulatory, and public level, considerable concern surrounds the concept that inappropriate exposure to endocrine-disrupting chemicals, especially during the prenatal and/or neonatal period, may disrupt normal reproductive tract development and adult function. The intent of this review was to 1. Describe some unique advantages of the hamster for perinatal endocrine disruptor (ED) studies, 2. Summarize the morphological and molecular consequences of exposure to the established perinatal ED, diethylstilbestrol, in the female and male hamster, 3. Present some new, histomorphological insight into the process of neonatal diethylstilbestrol-induced disruption in the hamster uterus, and 4. Introduce recent efforts and future plans to evaluate the potency and mechanism of action of other putative EDs in the hamster experimental system. Taken together, the findings indicate that the hamster represents a unique and sensitive in vivo system to probe the phenomenon of endocrine disruption. The spectrum of candidate endpoints includes developmental toxicity, neoplasia, and more subtle endpoints of reproductive dysfunction.

scholarly journals Effects of Polybrominated Diphenyl Ethers on Child Cognitive, Behavioral, and Motor Development

2018 ◽  
Vol 15 (8) ◽  
pp. 1636 ◽  
Author(s):  
Elizabeth Gibson ◽  
Eva Siegel ◽  
Folake Eniola ◽  
Julie Herbstman ◽  
Pam Factor-Litvak
Keyword(s):  
Thyroid Function ◽  
Motor Development ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Diphenyl Ether ◽  
Geographic Location ◽  
Maternal Blood ◽  
In Utero ◽  
Environmental Chemicals ◽  
Relevant Effect

Polybrominated Diphenyl Ether (PBDE) flame retardants are environmental chemicals that cross the placenta during pregnancy and have shown evidence of neurotoxicity. As the in utero period is a sensitive developmental window, such exposure may result in adverse childhood outcomes. Associations between in utero PBDE exposure and neurodevelopment are found in animal models and increasingly in human population studies. Here, we review the epidemiological evidence of the association between prenatal exposure to PBDEs and motor, cognitive, and behavioral development in infants and children. Published work suggests a negative association between PBDE concentrations and neurodevelopment despite varying PBDE congeners measured, bio-specimen matrix used, timing of the biological sampling, geographic location of study population, specific developmental tests used, age of children at time of testing, and statistical methodologies. This review includes 16 published studies that measured PBDE exposure in maternal blood during pregnancy or in cord blood at delivery and performed validated motor, cognitive, and/or behavioral testing at one or more time during childhood. We evaluate possible mediation through PBDE-induced perturbations in thyroid function and effect measure modification by child sex. While the majority of studies support an adverse association between PBDEs and neurodevelopment, additional research is required to understand the mechanism of action, possibly through the perturbations in thyroid function either in the pregnant woman or in the child, and the role of biologically relevant effect modifiers such as sex.

scholarly journals Human Excretion of Polybrominated Diphenyl Ether Flame Retardants: Blood, Urine, and Sweat Study

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Shelagh K. Genuis ◽  
Detlef Birkholz ◽  
Stephen J. Genuis
Keyword(s):  
Organic Pollutants ◽  
Persistent Organic Pollutants ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Diphenyl Ether ◽  
Body Fluids ◽  
Urine Samples ◽  
Health Implications ◽  
Reproductive Effects ◽  
Diphenyl Ethers

Commonly used as flame retardants, polybrominated diphenyl ethers (PBDEs) are routinely detected in the environment, animals, and humans. Although these persistent organic pollutants are increasingly recognized as having serious health implications, particularly for children, this is the first study, to our knowledge, to investigate an intervention for human elimination of bioaccumulated PBDEs. Objectives. To determine the efficacy of blood, urine, and perspiration as PBDE biomonitoring mediums; assess excretion of five common PBDE congeners (28, 47, 99, 100, and 153) in urine and perspiration; and explore the potential of induced sweating for decreasing bioaccumulated PBDEs. Results. PBDE congeners were not found in urine samples; findings focus on blood and perspiration. 80% of participants tested positive in one or more body fluids for PBDE 28, 100% for PBDE 47, 95% for PBDE 99, and 90% for PBDE 100 and PBDE 153. Induced perspiration facilitated excretion of the five congeners, with different rates of excretion for different congeners. Conclusion. Blood testing provides only a partial understanding of human PBDE bioaccumulation; testing of both blood and perspiration provides a better understanding. This study provides important baseline evidence for regular induced perspiration as a potential means for therapeutic PBDE elimination. Fetotoxic and reproductive effects of PBDE exposure highlight the importance of further detoxification research.

Exposure of alveolar macrophages to polybrominated diphenyl ethers suppresses the release of pro-inflammatory products in vitro

2012 ◽  
Vol 237 (4) ◽  
pp. 429-434 ◽  
Author(s):  
Stephen R Hennigar ◽  
Jay L Myers ◽  
Anthony R Tagliaferro
Keyword(s):  
Estrogen Receptor ◽  
Alveolar Macrophages ◽  
Polybrominated Diphenyl Ethers ◽  
Diphenyl Ether ◽  
Prostaglandin E ◽  
Tnf Α ◽  
Diphenyl Ethers ◽  
The Impact

Inhalation of chemical pollutants has been associated with a reduced immune response in humans. Inhalation of dust is a major route of exposure for one endocrine-disrupting chemical and suspected xenoestrogen, polybrominated diphenyl ethers (PBDEs); however, the impact of PBDEs on immune function is unclear. The objective of this study was to investigate the action of PBDEs on cytokine and eicosanoid release by alveolar macrophages and determine whether the effects are mediated via the estrogen receptor. The production of tumor necrosis factor (TNF)- α, interleukin (IL)-6, IL-1 β, IL-10 and prostaglandin E2 (PGE2) by porcine alveolar macrophages exposed to different concentrations of the pentabrominated diphenyl ether mixture, DE-71, were measured; cells were also exposed to varying concentrations of 17 β-estradiol and the selective estrogen receptor-modulating agent, tamoxifen. Cells exposed to PBDEs released significantly less pro-inflammatory cytokines (TNF- α and IL-6) and PGE2 compared with controls; IL-1 β and IL-10 were not detected in the culture medium. Cells exposed to 17 β-estradiol released significantly less TNF- α compared with controls, an effect that was reversed by the addition of tamoxifen; tamoxifen had no effect on the inhibition of TNF- α release by PBDEs. Although the suppression of TNF- α with DE-71 was similar to that of estrogen, the inhibitory effects of DE-71 were not found to be dependent on the estrogen receptor. Findings of this study suggest that chronic exposure to PBDEs suppressed innate immunity in vitro. Whether the immunosuppressant effects of PBDEs occur in vivo, remains to be determined.

scholarly journals SAT-723 Effects of Organohalogenated Endocrine Disrupting Chemicals on Cell Proliferation and Gene Expression in GH3 Somatolactotropes

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sophie Ringrose ◽  
Kyriakos Grammatopoulos ◽  
Natalie Welch ◽  
Bigboy Simbi ◽  
Stijn J Niessen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Polybrominated Diphenyl Ethers ◽  
Endocrine Disrupting Chemicals ◽  
Tumor Formation ◽  
Gh3 Cells ◽  
Phenol Red ◽  
Increased Risk ◽  
Endocrine Disrupting

Abstract Endocrine Disrupting Chemicals (EDCs) are substances that have been increasingly implicated in many serious pathologies, such as tumor formation, metabolic, growth and reproductive disorders. The economic and health burden of exposure to these compounds has an annual predicted cost in excess of €150 billion, across the EU regions alone. Of the growing list of compounds that act as EDCs, the organohalogenated compounds (OHCs), polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) have been associated with an increased risk of pituitary disease. We have previously reported that feline patients with hypersomatotropism (acromegaly) are exposed to elevated levels of PBDEs and PCBs in their environment. However, the mechanisms by which these compounds might directly influence somatotroph function have yet to be established. In this study, we use the GH3 rat somatolactotrope cell line to investigate how two PCB congeners - 138 and 153 - influence cell proliferation (using a Crystal Violet assay) and somatotrope gene expression (using a multiplex RT-qPCR approach to examine expression of Esr1, Esr2, Sstr1, Sstr2, Sstr3, Sstr4, Sstr5, Insr, Tshr, Pou1f1, Ghrhr2, Gh). GH3 cells were treated with Phenol Red-free media in the absence or presence of either PCB138 or 153 (-10 to -6 M), or in combination (-10 to -6M) for up to 72h. Treatment with either PCB alone, or in combination, caused significant concentration-dependent, biphasic changes in cell proliferation at each time point, but with a different profile of response on each day (significantly increased at high pM/low nM concentrations); there was no evidence of toxicity at maximum concentrations (-6M). Gene expression changes were determined in GH3 cells treated in the absence or presence of either -8M or -6M PCB138 or 153 for 24h. Differential effects of these compounds were seen on the expression of Sstr3, Sstr4, Sstr5 and Insr; all other gene transcripts were unaffected. These findings reveal that GH3 cells exposed to physiologically relevant concentrations of PCB138 and 153, alone or in combination, show concentration-dependent increases in cell proliferation; furthermore, the expression of genes associated with therapeutic targets for the treatment of acromegaly (i.e. SSTRs) are differentially affected by exposure to PCB138 and 153. Our data indicate a potential mechanism for EDCs in the onset of acromegaly, that require further, in vivo, investigations.

scholarly journals The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3466-3472 ◽  
Author(s):  
Jente Stel ◽  
Juliette Legler
Keyword(s):  
Gene Regulation ◽  
Early Life ◽  
Developmental Plasticity ◽  
Target Genes ◽  
Diphenyl Ether ◽  
Endocrine Disrupting Chemicals ◽  
Peroxisome Proliferator ◽  
Developmental Exposure ◽  
Endocrine Disrupting

Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.

scholarly journals Polybrominated diphenyl ethers perturb axonal growth and actin distribution

BIBECHANA ◽  
2018 ◽  
Vol 16 ◽  
pp. 64-78 ◽  
Author(s):  
Bhanu B Neupane ◽  
Tao Jin ◽  
Zhen Gu ◽  
Frances S Ligler ◽  
Gufeng Wang
Keyword(s):  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Calcium Release ◽  
Diphenyl Ether ◽  
Axonal Growth ◽  
Acute Exposure ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Exposure Conditions

We investigated toxicological effects of two of the most common polybrominated diphenyl ether (PBDE) flame retardants, BDE-47 and BDE-209, in model PC12 cell line under two environmentally relevant exposure conditions:  long term exposure to microgram-per-liter levels of PBDEs and acute exposure to high concentrations of PBDEs. Cells treated under both long term and acute exposure conditions showed significantly perturbed cell growth and differentiation. Importantly, even when the cells were exposed to microgram-per-liter concentration of PBDEs over an extended period, both the fraction of differentiated cells and the axonal growth were affected. The calcium release assay showed that PBDEs perturbed intracellular calcium release in a concentration dependent manner, indicating that intracellular Ca++ homeostasis and signaling was involved in the neurotoxicity. More interestingly, depending on PBDE concentration and exposure conditions, cytoskeleton F-actin distribution was altered.  BIBECHANA 16 (2019) 64-78

Evaluation of DNA Damage Induced by 2 Polybrominated Diphenyl Ether Flame Retardants (BDE-47 and BDE-209) in SK-N-MC Cells

2012 ◽  
Vol 31 (4) ◽  
pp. 372-379 ◽  
Author(s):  
Claudia Pellacani ◽  
Annamaria Buschini ◽  
Serena Galati ◽  
Francesca Mussi ◽  
Susanna Franzoni ◽  
...  
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Health Effects ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Diphenyl Ether ◽  
Human Neuroblastoma ◽  
Adverse Health Effects ◽  
Adverse Health ◽  
Bde 209

Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants whose levels have increased in the environment and in human tissues in the past decades. Exposure to PBDEs has been associated with developmental neurotoxicity, endocrine dysfunction, and reproductive disorders. In spite of their widespread distribution and potential adverse health effects, only few studies have addressed the potential neurotoxicity of PBDEs. In the present study, we evaluated the cyto- and genotoxicity of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) and decabrominated diphenyl ether (BDE-209) in human neuroblastoma cells (SK-N-MC). The DNA damage was measured using the alkaline version of the Comet assay, while specific oxidative-generated DNA damage was evaluated by a modified version of the Comet assay with the repair enzyme formamidopyrimidine glycosylase (FPG). The results show that BDE-47 and BDE-209 (5-20 μmol/L) are able to induce DNA damage in human SK-N-MC cells. Pretreatment with the antioxidant melatonin significantly reduced the DNA damage induced by both congeners. The Comet assay carried out in the presence of FPG suggests that both congeners increase purine oxidation. In all cases, BDE-47 was more potent than BDE-209. The results indicate that 2 environmentally relevant PBDEs cause DNA damage which is primarily mediated by the induction of oxidative stress and may contribute to adverse health effects.

A review on sources of brominated flame retardants and routes of human exposure with emphasis on polybrominated diphenyl ethers

2010 ◽  
Vol 18 (NA) ◽  
pp. 239-254 ◽  
Author(s):  
Adegbenro P. Daso ◽  
Olalekan S. Fatoki ◽  
James P. Odendaal ◽  
Jonathan O. Okonkwo
Keyword(s):  
Polybrominated Diphenyl Ethers ◽  
Human Exposure ◽  
Flame Retardants ◽  
Diphenyl Ether ◽  
Brominated Flame Retardants ◽  
Dermal Absorption ◽  
Indoor Dust ◽  
Indoor Environments ◽  
Human Tissues ◽  
Environmental Matrices

The presence of brominated flame retardants (BFRs) in various environmental matrices, including humans, has been well documented. Increasing levels of these emerging contaminants in various environmental compartments suggest the wide application of these chemicals in products of everyday use. The release of BFRs from treated products is generally believed to be the major source of these contaminants into the environment, particularly in indoor environments. The sources and pathways through which BFRs enter the human system are evaluated in this paper. Human exposure via consumption of contaminated food and water, inhalation and ingestion of dust, as well as dermal absorption, are important pathways for these contaminants. Consumption of fatty foods especially fish, meat, dairy products as well as human milk constitute important routes for human exposure to these contaminants. Although brominated diphenyl ether (BDE) 209 has been found to be less bioaccumulative due to its high molecular weight, its dominance in indoor dust samples could be responsible for its detection in most human tissues investigated. BDE 47 is the most dominant polybrominated diphenyl ether (PBDE) congener found in human tissues. Regional differences in BFR levels in various environmental and biological matrices reflect their consumption patterns with higher levels mostly reported in the North American environments than in other regions of the world.

scholarly journals Experimental Approaches for Characterizing the Endocrine-Disrupting Effects of Environmental Chemicals in Fish

2021 ◽  
Vol 11 ◽  
Author(s):  
Fritzie T. Celino-Brady ◽  
Darren T. Lerner ◽  
Andre P. Seale
Keyword(s):  
Developmental Stages ◽  
Endocrine Disrupting Chemicals ◽  
Endocrine System ◽  
Environmental Chemicals ◽  
Endocrine Disrupting ◽  
Aquatic Vertebrates ◽  
In The Wild ◽  
Experimental Approaches

Increasing industrial and agricultural activities have led to a disturbing increase of pollutant discharges into the environment. Most of these pollutants can induce short-term, sustained or delayed impacts on developmental, physiological, and behavioral processes that are often regulated by the endocrine system in vertebrates, including fish, thus they are termed endocrine-disrupting chemicals (EDCs). Physiological impacts resulting from the exposure of these vertebrates to EDCs include abnormalities in growth and reproductive development, as many of the prevalent chemicals are capable of binding the receptors to sex steroid hormones. The approaches employed to investigate the action and impact of EDCs is largely dependent on the specific life history and habitat of each species, and the type of chemical that organisms are exposed to. Aquatic vertebrates, such as fish, are among the first organisms to be affected by waterborne EDCs, an attribute that has justified their wide-spread use as sentinel species. Many fish species are exposed to these chemicals in the wild, for either short or prolonged periods as larvae, adults, or both, thus, studies are typically designed to focus on either acute or chronic exposure at distinct developmental stages. The aim of this review is to provide an overview of the approaches and experimental methods commonly used to characterize the effects of some of the environmentally prevalent and emerging EDCs, including 17 α-ethinylestradiol, nonylphenol, BPA, phthalates, and arsenic; and the pervasive and potential carriers of EDCs, microplastics, on reproduction and growth. In vivo and in vitro studies are designed and employed to elucidate the direct effects of EDCs at the organismal and cellular levels, respectively. In silico approaches, on the other hand, comprise computational methods that have been more recently applied with the potential to replace extensive in vitro screening of EDCs. These approaches are discussed in light of model species, age and duration of EDC exposure.

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