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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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 |
format | Article |
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•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. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-9d64d36d6518fdcadbaa09a80936acb344ec0351c3633ae1c90b52187d6b365b3</citedby><cites>FETCH-LOGICAL-c513t-9d64d36d6518fdcadbaa09a80936acb344ec0351c3633ae1c90b52187d6b365b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2014.03.028$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,778,782,883,3539,27913,27914,45984</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28513137$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24726521$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22439739$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Crump, Doug</creatorcontrib><creatorcontrib>Porter, Emily</creatorcontrib><creatorcontrib>Egloff, Caroline</creatorcontrib><creatorcontrib>Williams, Kim L.</creatorcontrib><creatorcontrib>Letcher, Robert J.</creatorcontrib><creatorcontrib>Gauthier, Lewis T.</creatorcontrib><creatorcontrib>Kennedy, Sean W.</creatorcontrib><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</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><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.</description><subject>1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane</subject><subject>60 APPLIED LIFE SCIENCES</subject><subject>ADDITIVES</subject><subject>Animals</subject><subject>BILE ACIDS</subject><subject>Bile Acids and Salts - blood</subject><subject>Bile Acids and Salts - metabolism</subject><subject>Biological and medical sciences</subject><subject>Bridged Bicyclo Compounds, Heterocyclic - toxicity</subject><subject>Chick Embryo</subject><subject>Chicken</subject><subject>CHICKENS</subject><subject>CONCENTRATION RATIO</subject><subject>CYCLOHEXANE</subject><subject>Cyclohexanes - toxicity</subject><subject>Embryonic development</subject><subject>EMBRYOS</subject><subject>Environmental Pollutants - toxicity</subject><subject>Flame Retardants - toxicity</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>GENES</subject><subject>IN VITRO</subject><subject>LIPIDS</subject><subject>LIVER</subject><subject>Liver - metabolism</subject><subject>LIVER CELLS</subject><subject>Medical sciences</subject><subject>MESSENGER-RNA</subject><subject>METABOLISM</subject><subject>Molecular Structure</subject><subject>mRNA expression</subject><subject>ONTOGENESIS</subject><subject>PHOSPHATES</subject><subject>PLANT GROWTH</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>SCREENING</subject><subject>THYROID HORMONES</subject><subject>Thyroxine - blood</subject><subject>TOXICITY</subject><subject>Toxicology</subject><subject>Tris(methylphenyl) phosphate</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV2L1DAUhoso7rj6B7yQgAgjTMd8dDIteLOsn7AoiIJ3IT053WZsk5pklp3_5w8z3Rn1zqtwTp7z9b5F8ZTRNaNMvtqtk9bTmlNWralYU17fKxaMNrKkQoj7xYLSipWU1t_Pikcx7iilTVWxh8UZr7ZcbjhbFL_YipdvbBv86MuqXM6hOYaY-sPwsoQDDL7HW-2QaGdICjYux7vPqUeXETL1Pk69TkhA7yOSaK-d7Sxolwh2HUKKxDti8AYHP43o0oqMXz5dELydAsZovVvd9QYbYD_oZN01ae2QB4LNWe8g14Sc9y4S6wj0Fn6gIzi24eDj4-JBp4eIT07vefHt3duvlx_Kq8_vP15eXJWwYSKVjZGVEdLIDas7A9q0WtNG17QRUkMrqgqBig0DIYXQyKChbRap3hrZCrlpxXnx_NjXx2RVBJsQ-rydyxcqzivRbEWTqeWRmoL_uceY1Ggj4DBkBf0-KiY5l5TnJTLKjygEH2PATk3BjjocFKNq9ljt1Oyxmj1WVKjscS56duq_b0c0f0v-mJqBFydAR9BDF7QDG_9xdVaDiW3mXh85zJrdWAzzSZi1NjbMFxlv_7fHbxqXx7s</recordid><startdate>20140615</startdate><enddate>20140615</enddate><creator>Crump, Doug</creator><creator>Porter, Emily</creator><creator>Egloff, Caroline</creator><creator>Williams, Kim L.</creator><creator>Letcher, Robert J.</creator><creator>Gauthier, Lewis T.</creator><creator>Kennedy, Sean W.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7ST</scope><scope>7U7</scope><scope>C1K</scope><scope>SOI</scope><scope>OTOTI</scope></search><sort><creationdate>20140615</creationdate><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</title><author>Crump, Doug ; Porter, Emily ; Egloff, Caroline ; Williams, Kim L. ; Letcher, Robert J. ; Gauthier, Lewis T. ; Kennedy, Sean W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-9d64d36d6518fdcadbaa09a80936acb344ec0351c3633ae1c90b52187d6b365b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane</topic><topic>60 APPLIED LIFE SCIENCES</topic><topic>ADDITIVES</topic><topic>Animals</topic><topic>BILE ACIDS</topic><topic>Bile Acids and Salts - blood</topic><topic>Bile Acids and Salts - metabolism</topic><topic>Biological and medical sciences</topic><topic>Bridged Bicyclo Compounds, Heterocyclic - toxicity</topic><topic>Chick Embryo</topic><topic>Chicken</topic><topic>CHICKENS</topic><topic>CONCENTRATION RATIO</topic><topic>CYCLOHEXANE</topic><topic>Cyclohexanes - toxicity</topic><topic>Embryonic development</topic><topic>EMBRYOS</topic><topic>Environmental Pollutants - toxicity</topic><topic>Flame Retardants - toxicity</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>GENES</topic><topic>IN VITRO</topic><topic>LIPIDS</topic><topic>LIVER</topic><topic>Liver - metabolism</topic><topic>LIVER CELLS</topic><topic>Medical sciences</topic><topic>MESSENGER-RNA</topic><topic>METABOLISM</topic><topic>Molecular Structure</topic><topic>mRNA expression</topic><topic>ONTOGENESIS</topic><topic>PHOSPHATES</topic><topic>PLANT GROWTH</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>SCREENING</topic><topic>THYROID HORMONES</topic><topic>Thyroxine - blood</topic><topic>TOXICITY</topic><topic>Toxicology</topic><topic>Tris(methylphenyl) phosphate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Crump, Doug</creatorcontrib><creatorcontrib>Porter, Emily</creatorcontrib><creatorcontrib>Egloff, Caroline</creatorcontrib><creatorcontrib>Williams, Kim L.</creatorcontrib><creatorcontrib>Letcher, Robert J.</creatorcontrib><creatorcontrib>Gauthier, Lewis T.</creatorcontrib><creatorcontrib>Kennedy, Sean W.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Crump, Doug</au><au>Porter, Emily</au><au>Egloff, Caroline</au><au>Williams, Kim L.</au><au>Letcher, Robert J.</au><au>Gauthier, Lewis T.</au><au>Kennedy, Sean W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2014-06-15</date><risdate>2014</risdate><volume>277</volume><issue>3</issue><spage>279</spage><epage>287</epage><pages>279-287</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>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.</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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