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  1. Article ; Online: Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows.

    Noyes, Pamela D / Lema, Sean C / Macaulay, Laura J / Douglas, Nora K / Stapleton, Heather M

    Environmental science & technology

    2013  Volume 47, Issue 17, Page(s) 10012–10021

    Abstract: Polybrominated diphenyl ether (PBDE) flame retardants have been shown to disrupt thyroid hormone regulation, neurodevelopment, and reproduction in some animals. However, effects of the most heavily used PBDE, decabromodiphenyl ether (BDE-209), on thyroid ...

    Abstract Polybrominated diphenyl ether (PBDE) flame retardants have been shown to disrupt thyroid hormone regulation, neurodevelopment, and reproduction in some animals. However, effects of the most heavily used PBDE, decabromodiphenyl ether (BDE-209), on thyroid functioning remain unclear. This study examined low-dose effects of BDE-209 on thyroid hormone levels and signaling in fathead minnows. Adult males received dietary exposures of BDE-209 at a low dose (∼3 ng/g bw-day) and high dose (∼300 ng/g bw-day) for 28 days followed by a 14-day depuration to evaluate recovery. Compared to controls, fish exposed to the low dose for 28 days experienced a 53% and 46% decline in circulating total thyroxine (TT4) and 3,5,3'-triiodothyronine (TT3), respectively, while TT4 and TT3 deficits at the high dose were 59% and 62%. Brain deiodinase activity (T4-ORD) was reduced by ∼65% at both doses. BDE-209 elevated the relative mRNA expression of genes encoding deiodinases, nuclear thyroid receptors, and membrane transporters in the brain and liver in patterns that varied with time and dose, likely in compensation to hypothyroidism. Declines in the gonadal-somatic index (GSI) and increased mortality were also measured. Effects at the low dose were consistent with the high dose, suggesting nonlinear relationships between BDE-209 exposures and thyroid dysfunction.
    MeSH term(s) Animals ; Body Composition/drug effects ; Brain/drug effects ; Brain/metabolism ; Cyprinidae/genetics ; Cyprinidae/physiology ; DNA, Complementary/genetics ; DNA, Complementary/metabolism ; Dose-Response Relationship, Drug ; Fish Proteins/metabolism ; Flame Retardants/metabolism ; Flame Retardants/toxicity ; Gas Chromatography-Mass Spectrometry ; Gene Expression Regulation ; Halogenated Diphenyl Ethers/metabolism ; Halogenated Diphenyl Ethers/toxicity ; Iodide Peroxidase/metabolism ; Liver/drug effects ; Liver/metabolism ; Male ; Membrane Proteins/metabolism ; Molecular Sequence Data ; Polymerase Chain Reaction ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Random Allocation ; Receptors, Thyroid Hormone/metabolism ; Reproduction/drug effects ; Sequence Analysis, DNA ; Signal Transduction/drug effects ; Thyroid Hormones/metabolism ; Water Pollutants, Chemical/metabolism ; Water Pollutants, Chemical/toxicity
    Chemical Substances DNA, Complementary ; Fish Proteins ; Flame Retardants ; Halogenated Diphenyl Ethers ; Membrane Proteins ; RNA, Messenger ; Receptors, Thyroid Hormone ; Thyroid Hormones ; Water Pollutants, Chemical ; Iodide Peroxidase (EC 1.11.1.8) ; decabromobiphenyl ether (N80BQ29A0H)
    Language English
    Publishing date 2013-08-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1520-5851
    ISSN (online) 1520-5851
    DOI 10.1021/es402650x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Low Level Exposure to the Flame Retardant BDE-209 Reduces Thyroid Hormone Levels and Disrupts Thyroid Signaling in Fathead Minnows

    Noyes, PamelaD / Lema, Sean C / Macaulay, Laura J / Douglas, Nora K / Stapleton, Heather M

    Environmental Science & Technology. 2013 Sept. 03, v. 47, no. 17

    2013  

    Abstract: Polybrominated diphenyl ether (PBDE) flame retardants have been shown to disrupt thyroid hormone regulation, neurodevelopment, and reproduction in some animals. However, effects of the most heavily used PBDE, decabromodiphenyl ether (BDE-209), on thyroid ...

    Abstract Polybrominated diphenyl ether (PBDE) flame retardants have been shown to disrupt thyroid hormone regulation, neurodevelopment, and reproduction in some animals. However, effects of the most heavily used PBDE, decabromodiphenyl ether (BDE-209), on thyroid functioning remain unclear. This study examined low-dose effects of BDE-209 on thyroid hormone levels and signaling in fathead minnows. Adult males received dietary exposures of BDE-209 at a low dose (∼3 ng/g bw-day) and high dose (∼300 ng/g bw-day) for 28 days followed by a 14-day depuration to evaluate recovery. Compared to controls, fish exposed to the low dose for 28 days experienced a 53% and 46% decline in circulating total thyroxine (TT4) and 3,5,3′-triiodothyronine (TT3), respectively, while TT4 and TT3 deficits at the high dose were 59% and 62%. Brain deiodinase activity (T4-ORD) was reduced by ∼65% at both doses. BDE-209 elevated the relative mRNA expression of genes encoding deiodinases, nuclear thyroid receptors, and membrane transporters in the brain and liver in patterns that varied with time and dose, likely in compensation to hypothyroidism. Declines in the gonadal-somatic index (GSI) and increased mortality were also measured. Effects at the low dose were consistent with the high dose, suggesting nonlinear relationships between BDE-209 exposures and thyroid dysfunction.
    Keywords adults ; brain ; fish ; flame retardants ; gene expression ; hypothyroidism ; liver ; males ; messenger RNA ; mortality ; neurodevelopment ; polybrominated diphenyl ethers ; receptors ; reproduction ; thyroid function ; thyroid hormones ; thyroxine ; transporters
    Language English
    Dates of publication 2013-0903
    Size p. 10012-10021.
    Publishing place American Chemical Society
    Document type Article
    ISSN 1520-5851
    DOI 10.1021%2Fes402650x
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Gene transcription, metabolite and lipid profiling in eco-indicator daphnia magna indicate diverse mechanisms of toxicity by legacy and emerging flame-retardants.

    Scanlan, Leona D / Loguinov, Alexandre V / Teng, Quincy / Antczak, Philipp / Dailey, Kathleen P / Nowinski, Daniel T / Kornbluh, Jonah / Lin, Xin Xin / Lachenauer, Erica / Arai, Audrey / Douglas, Nora K / Falciani, Francesco / Stapleton, Heather M / Vulpe, Chris D

    Environmental science & technology

    2015  Volume 49, Issue 12, Page(s) 7400–7410

    Abstract: The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address ... ...

    Abstract The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address this issue, the toxicity of seven FR chemicals and formulations was assessed on the freshwater crustacean Daphnia magna. Acute 48-h nominal LC50 values for penta- and octabromodiphenyl ether (pentaBDE, octaBDE), Firemaster 550 (FM550), Firemaster BZ-54 (BZ54), bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), triphenyl phosphate (TPhP), and nonbrominated BEH-TEBP analog bis(2-ethylhexyl) phthalate (BEHP) ranged from 0.058 mg/L (pentaBDE) to 3.96 mg/L (octaBDE). mRNA expression, (1)H NMR-based metabolomic and lipidomic profiling at 1/10 LC50 revealed distinct patterns of molecular response for each exposure, suggesting pentaPBDE affects transcription and translation, octaBDE and BEH-TEBP affect glycosphingolipid biosynthesis and BZ54 affects Wnt and Hedgehog signal pathways as well as glycosaminoglycan degradation. Brominated components of FM550 (i.e., BZ54) were significantly higher in Daphnia after 48 h following 1/10 LC50 exposure. FM550 elicited significant mRNA changes at five concentrations across a range from 1/10(6) LC50 to 1/2 LC50. Analyses suggest FM550 impairs nutrient utilization or uptake in Daphnia.
    MeSH term(s) Animals ; Biomarkers/metabolism ; Cluster Analysis ; Daphnia/drug effects ; Daphnia/genetics ; Daphnia/metabolism ; Environmental Exposure/analysis ; Flame Retardants/toxicity ; Gene Expression Profiling ; Lipid Metabolism/drug effects ; Lipid Metabolism/genetics ; Metabolome/drug effects ; Metabolome/genetics ; Metabolomics ; Proton Magnetic Resonance Spectroscopy ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcription, Genetic/drug effects
    Chemical Substances Biomarkers ; Flame Retardants ; RNA, Messenger
    Language English
    Publishing date 2015-06-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1520-5851
    ISSN (online) 1520-5851
    DOI 10.1021/acs.est.5b00977
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Gene Transcription, Metabolite and Lipid Profiling in Eco-Indicator Daphnia magna Indicate Diverse Mechanisms of Toxicity by Legacy and Emerging Flame-Retardants

    Scanlan, LeonaD / Loguinov, Alexandre V / Teng, Quincy / Antczak, Philipp / Dailey, KathleenP / Nowinski, Daniel T / Kornbluh, Jonah / Lin, Xin Xin / Lachenauer, Erica / Arai, Audrey / Douglas, Nora K / Falciani, Francesco / Stapleton, Heather M / Vulpe, Chris D

    Environmental Science & Technology. 2015 June 16, v. 49, no. 12

    2015  

    Abstract: The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address ... ...

    Abstract The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address this issue, the toxicity of seven FR chemicals and formulations was assessed on the freshwater crustacean Daphnia magna. Acute 48-h nominal LC50 values for penta- and octabromodiphenyl ether (pentaBDE, octaBDE), Firemaster 550 (FM550), Firemaster BZ-54 (BZ54), bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), triphenyl phosphate (TPhP), and nonbrominated BEH-TEBP analog bis(2-ethylhexyl) phthalate (BEHP) ranged from 0.058 mg/L (pentaBDE) to 3.96 mg/L (octaBDE). mRNA expression, 1H NMR-based metabolomic and lipidomic profiling at 1/10 LC50 revealed distinct patterns of molecular response for each exposure, suggesting pentaPBDE affects transcription and translation, octaBDE and BEH-TEBP affect glycosphingolipid biosynthesis and BZ54 affects Wnt and Hedgehog signal pathways as well as glycosaminoglycan degradation. Brominated components of FM550 (i.e., BZ54) were significantly higher in Daphnia after 48 h following 1/10 LC50 exposure. FM550 elicited significant mRNA changes at five concentrations across a range from 1/106 LC50 to 1/2 LC50. Analyses suggest FM550 impairs nutrient utilization or uptake in Daphnia.
    Keywords Daphnia magna ; biosynthesis ; flame retardants ; freshwater crustaceans ; gene expression ; glycosaminoglycans ; lethal concentration 50 ; lipid composition ; messenger RNA ; metabolites ; metabolomics ; nutrient utilization ; phosphates ; phthalates ; signal transduction ; toxicity ; transcription (genetics) ; translation (genetics)
    Language English
    Dates of publication 2015-0616
    Size p. 7400-7410.
    Publishing place American Chemical Society
    Document type Article
    ISSN 1520-5851
    DOI 10.1021%2Facs.est.5b00977
    Database NAL-Catalogue (AGRICOLA)

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