1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane and tris(methylphenyl) phosphate cause significant effects on development, mRNA expression, and circulating bile acid concentrations in chicken embryos

1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane (DBE-DBCH; formerly abbreviated as TBECH) and tris(methylphenyl) phosphate (TMPP; formerly abbreviated as TCP) are additive flame retardants that are detected in the environment and biota. A recent avian in vitro screening study of 16 flame retardants ide...

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Veröffentlicht in:Toxicology and applied pharmacology 2014-06, Vol.277 (3), p.279-287
Hauptverfasser: Crump, Doug, Porter, Emily, Egloff, Caroline, Williams, Kim L., Letcher, Robert J., Gauthier, Lewis T., Kennedy, Sean W.
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container_end_page 287
container_issue 3
container_start_page 279
container_title Toxicology and applied pharmacology
container_volume 277
creator Crump, Doug
Porter, Emily
Egloff, Caroline
Williams, Kim L.
Letcher, Robert J.
Gauthier, Lewis T.
Kennedy, Sean W.
description 1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane (DBE-DBCH; formerly abbreviated as TBECH) and tris(methylphenyl) phosphate (TMPP; formerly abbreviated as TCP) are additive flame retardants that are detected in the environment and biota. A recent avian in vitro screening study of 16 flame retardants identified DBE-DBCH and TMPP as important chemicals for follow-up in ovo evaluation based on their effects on cytotoxicity and mRNA expression in avian hepatocytes. In this study, technical mixtures of DBE-DBCH and TMPP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 54,900ng/g and from 0 to 261,400ng/g, respectively, to determine effects on pipping success, development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations. Both compounds were detectable in embryos at pipping and the β-DBE-DBCH isomer was depleted more rapidly than the α-isomer in tissue samples. DBE-DBCH had limited effects on the endpoints measured, with the exception of the up-regulation of two phase I metabolizing enzymes, CYP3A37 and CYP2H1. TMPP exposure caused embryonic deformities, altered growth, increased liver somatic index (LSI) and plasma bile acid concentrations, and altered mRNA expression levels of genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Overall, TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH albeit at concentrations several orders of magnitude greater than those detected in the environment. The increase in plasma bile acid concentrations was a useful phenotypic anchor as it was associated with a concomitant increase in LSI, discoloration of the liver tissue, and modulation of hepatic genes involved with xenobiotic and lipid metabolism. •DBE-DBCH and TMPP are not embryolethal to chicken embryos.•TMPP caused deformities, morphometric alterations, and increased plasma bile acids.•DBE-DBCH and TMPP altered mRNA levels of xenobiotic and lipid metabolism genes.•Elevated plasma bile acids suggest that TMPP causes liver dysfunction.•TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH.
doi_str_mv 10.1016/j.taap.2014.03.028
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A recent avian in vitro screening study of 16 flame retardants identified DBE-DBCH and TMPP as important chemicals for follow-up in ovo evaluation based on their effects on cytotoxicity and mRNA expression in avian hepatocytes. In this study, technical mixtures of DBE-DBCH and TMPP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 54,900ng/g and from 0 to 261,400ng/g, respectively, to determine effects on pipping success, development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations. Both compounds were detectable in embryos at pipping and the β-DBE-DBCH isomer was depleted more rapidly than the α-isomer in tissue samples. DBE-DBCH had limited effects on the endpoints measured, with the exception of the up-regulation of two phase I metabolizing enzymes, CYP3A37 and CYP2H1. TMPP exposure caused embryonic deformities, altered growth, increased liver somatic index (LSI) and plasma bile acid concentrations, and altered mRNA expression levels of genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Overall, TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH albeit at concentrations several orders of magnitude greater than those detected in the environment. The increase in plasma bile acid concentrations was a useful phenotypic anchor as it was associated with a concomitant increase in LSI, discoloration of the liver tissue, and modulation of hepatic genes involved with xenobiotic and lipid metabolism. •DBE-DBCH and TMPP are not embryolethal to chicken embryos.•TMPP caused deformities, morphometric alterations, and increased plasma bile acids.•DBE-DBCH and TMPP altered mRNA levels of xenobiotic and lipid metabolism genes.•Elevated plasma bile acids suggest that TMPP causes liver dysfunction.•TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2014.03.028</identifier><identifier>PMID: 24726521</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane ; 60 APPLIED LIFE SCIENCES ; ADDITIVES ; Animals ; BILE ACIDS ; Bile Acids and Salts - blood ; Bile Acids and Salts - metabolism ; Biological and medical sciences ; Bridged Bicyclo Compounds, Heterocyclic - toxicity ; Chick Embryo ; Chicken ; CHICKENS ; CONCENTRATION RATIO ; CYCLOHEXANE ; Cyclohexanes - toxicity ; Embryonic development ; EMBRYOS ; Environmental Pollutants - toxicity ; Flame Retardants - toxicity ; Gene Expression Regulation, Developmental - drug effects ; GENES ; IN VITRO ; LIPIDS ; LIVER ; Liver - metabolism ; LIVER CELLS ; Medical sciences ; MESSENGER-RNA ; METABOLISM ; Molecular Structure ; mRNA expression ; ONTOGENESIS ; PHOSPHATES ; PLANT GROWTH ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; SCREENING ; THYROID HORMONES ; Thyroxine - blood ; TOXICITY ; Toxicology ; Tris(methylphenyl) phosphate</subject><ispartof>Toxicology and applied pharmacology, 2014-06, Vol.277 (3), p.279-287</ispartof><rights>2014</rights><rights>2015 INIST-CNRS</rights><rights>Crown Copyright © 2014. 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TMPP exposure caused embryonic deformities, altered growth, increased liver somatic index (LSI) and plasma bile acid concentrations, and altered mRNA expression levels of genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Overall, TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH albeit at concentrations several orders of magnitude greater than those detected in the environment. 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formerly abbreviated as TBECH) and tris(methylphenyl) phosphate (TMPP; formerly abbreviated as TCP) are additive flame retardants that are detected in the environment and biota. A recent avian in vitro screening study of 16 flame retardants identified DBE-DBCH and TMPP as important chemicals for follow-up in ovo evaluation based on their effects on cytotoxicity and mRNA expression in avian hepatocytes. In this study, technical mixtures of DBE-DBCH and TMPP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 54,900ng/g and from 0 to 261,400ng/g, respectively, to determine effects on pipping success, development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations. Both compounds were detectable in embryos at pipping and the β-DBE-DBCH isomer was depleted more rapidly than the α-isomer in tissue samples. DBE-DBCH had limited effects on the endpoints measured, with the exception of the up-regulation of two phase I metabolizing enzymes, CYP3A37 and CYP2H1. TMPP exposure caused embryonic deformities, altered growth, increased liver somatic index (LSI) and plasma bile acid concentrations, and altered mRNA expression levels of genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Overall, TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH albeit at concentrations several orders of magnitude greater than those detected in the environment. The increase in plasma bile acid concentrations was a useful phenotypic anchor as it was associated with a concomitant increase in LSI, discoloration of the liver tissue, and modulation of hepatic genes involved with xenobiotic and lipid metabolism. •DBE-DBCH and TMPP are not embryolethal to chicken embryos.•TMPP caused deformities, morphometric alterations, and increased plasma bile acids.•DBE-DBCH and TMPP altered mRNA levels of xenobiotic and lipid metabolism genes.•Elevated plasma bile acids suggest that TMPP causes liver dysfunction.•TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>24726521</pmid><doi>10.1016/j.taap.2014.03.028</doi><tpages>9</tpages></addata></record>
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subjects 1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane
60 APPLIED LIFE SCIENCES
ADDITIVES
Animals
BILE ACIDS
Bile Acids and Salts - blood
Bile Acids and Salts - metabolism
Biological and medical sciences
Bridged Bicyclo Compounds, Heterocyclic - toxicity
Chick Embryo
Chicken
CHICKENS
CONCENTRATION RATIO
CYCLOHEXANE
Cyclohexanes - toxicity
Embryonic development
EMBRYOS
Environmental Pollutants - toxicity
Flame Retardants - toxicity
Gene Expression Regulation, Developmental - drug effects
GENES
IN VITRO
LIPIDS
LIVER
Liver - metabolism
LIVER CELLS
Medical sciences
MESSENGER-RNA
METABOLISM
Molecular Structure
mRNA expression
ONTOGENESIS
PHOSPHATES
PLANT GROWTH
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
SCREENING
THYROID HORMONES
Thyroxine - blood
TOXICITY
Toxicology
Tris(methylphenyl) phosphate
title 1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane and tris(methylphenyl) phosphate cause significant effects on development, mRNA expression, and circulating bile acid concentrations in chicken embryos
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