A physiologically based pharmacokinetic model for developmental exposure to BDE-47 in rats
Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments, where they have the potential to bioaccumulate in wildlife and humans. Of the 209 possible PBDEs, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is...
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| creator | Emond, Claude Raymer, James H. Studabaker, William B. Garner, C. Edwin Birnbaum, Linda S. |
| description | Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments, where they have the potential to bioaccumulate in wildlife and humans. Of the 209 possible PBDEs, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is usually the dominant congener found in human blood and milk samples. BDE-47 has been shown to have endocrine activity and produce developmental, reproductive, and neurotoxic effects. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for BDE-47 in male and female (pregnant and non-pregnant) adult rats to facilitate investigations of developmental exposure. This model consists of eight compartments: liver, brain, adipose tissue, kidney, placenta, fetus, blood, and the rest of the body. Concentrations of BDE-47 from the literature and from maternal–fetal pharmacokinetic studies conducted at RTI International were used to parameterize and evaluate the model. The results showed that the model simulated BDE-47 tissue concentrations in adult male, maternal, and fetal compartments within the standard deviations of the experimental data. The model's ability to estimate BDE-47 concentrations in the fetus after maternal exposure will be useful to design in utero exposure/effect studies. This PBPK model is the first one designed for any PBDE pharmaco/toxicokinetic description. The next steps will be to expand this model to simulate BDE-47 pharmacokinetics and distributions across species (mice), and then extrapolate it to humans. After mouse and human model development, additional PBDE congeners will be incorporated into the model and simulated as a mixture. |
| doi_str_mv | 10.1016/j.taap.2009.10.019 |
| format | Article |
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Edwin ; Birnbaum, Linda S.</creator><creatorcontrib>Emond, Claude ; Raymer, James H. ; Studabaker, William B. ; Garner, C. Edwin ; Birnbaum, Linda S.</creatorcontrib><description>Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments, where they have the potential to bioaccumulate in wildlife and humans. Of the 209 possible PBDEs, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is usually the dominant congener found in human blood and milk samples. BDE-47 has been shown to have endocrine activity and produce developmental, reproductive, and neurotoxic effects. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for BDE-47 in male and female (pregnant and non-pregnant) adult rats to facilitate investigations of developmental exposure. This model consists of eight compartments: liver, brain, adipose tissue, kidney, placenta, fetus, blood, and the rest of the body. Concentrations of BDE-47 from the literature and from maternal–fetal pharmacokinetic studies conducted at RTI International were used to parameterize and evaluate the model. The results showed that the model simulated BDE-47 tissue concentrations in adult male, maternal, and fetal compartments within the standard deviations of the experimental data. The model's ability to estimate BDE-47 concentrations in the fetus after maternal exposure will be useful to design in utero exposure/effect studies. This PBPK model is the first one designed for any PBDE pharmaco/toxicokinetic description. The next steps will be to expand this model to simulate BDE-47 pharmacokinetics and distributions across species (mice), and then extrapolate it to humans. After mouse and human model development, additional PBDE congeners will be incorporated into the model and simulated as a mixture.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2009.10.019</identifier><identifier>PMID: 19883674</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ADIPOSE TISSUE ; ANIMAL TISSUES ; ANIMALS ; AROMATICS ; BDE-47 ; Biological and medical sciences ; BODY ; BRAIN ; BROMINATED AROMATIC HYDROCARBONS ; CENTRAL NERVOUS SYSTEM ; CONNECTIVE TISSUE ; Developmental exposure ; DIGESTIVE SYSTEM ; Environmental Pollutants - pharmacokinetics ; ETHERS ; Female ; FETAL MEMBRANES ; Fetus - metabolism ; FETUSES ; GLANDS ; HALOGENATED AROMATIC HYDROCARBONS ; Halogenated Diphenyl Ethers ; Humans ; KIDNEYS ; LIVER ; Male ; MALES ; MAMMALS ; MAN ; Maternal Exposure ; Maternal-Fetal Exchange ; Medical sciences ; MEMBRANES ; MEN ; Models, Biological ; NERVOUS SYSTEM ; ORGANIC BROMINE COMPOUNDS ; ORGANIC COMPOUNDS ; ORGANIC HALOGEN COMPOUNDS ; ORGANIC OXYGEN COMPOUNDS ; ORGANS ; PBPK ; Pharmacokinetics ; PHENYL ETHER ; PLACENTA ; Polybrominated Biphenyls - pharmacokinetics ; Polybrominated diphenyl ethers ; Pregnancy ; PRIMATES ; Rat ; RATS ; Rats, Sprague-Dawley ; RODENTS ; SIMULATION ; Species Specificity ; Tissue Distribution ; TOXICITY ; Toxicology ; VERTEBRATES</subject><ispartof>Toxicology and applied pharmacology, 2010-02, Vol.242 (3), p.290-298</ispartof><rights>2009 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2009 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-7c5f8bd56ea219f46e3dce06dac3ec4e241c53553defbdead2781763410e46633</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2009.10.019$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22352577$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19883674$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/21344851$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Emond, Claude</creatorcontrib><creatorcontrib>Raymer, James H.</creatorcontrib><creatorcontrib>Studabaker, William B.</creatorcontrib><creatorcontrib>Garner, C. Edwin</creatorcontrib><creatorcontrib>Birnbaum, Linda S.</creatorcontrib><title>A physiologically based pharmacokinetic model for developmental exposure to BDE-47 in rats</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments, where they have the potential to bioaccumulate in wildlife and humans. Of the 209 possible PBDEs, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is usually the dominant congener found in human blood and milk samples. BDE-47 has been shown to have endocrine activity and produce developmental, reproductive, and neurotoxic effects. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for BDE-47 in male and female (pregnant and non-pregnant) adult rats to facilitate investigations of developmental exposure. This model consists of eight compartments: liver, brain, adipose tissue, kidney, placenta, fetus, blood, and the rest of the body. Concentrations of BDE-47 from the literature and from maternal–fetal pharmacokinetic studies conducted at RTI International were used to parameterize and evaluate the model. The results showed that the model simulated BDE-47 tissue concentrations in adult male, maternal, and fetal compartments within the standard deviations of the experimental data. The model's ability to estimate BDE-47 concentrations in the fetus after maternal exposure will be useful to design in utero exposure/effect studies. This PBPK model is the first one designed for any PBDE pharmaco/toxicokinetic description. The next steps will be to expand this model to simulate BDE-47 pharmacokinetics and distributions across species (mice), and then extrapolate it to humans. After mouse and human model development, additional PBDE congeners will be incorporated into the model and simulated as a mixture.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ADIPOSE TISSUE</subject><subject>ANIMAL TISSUES</subject><subject>ANIMALS</subject><subject>AROMATICS</subject><subject>BDE-47</subject><subject>Biological and medical sciences</subject><subject>BODY</subject><subject>BRAIN</subject><subject>BROMINATED AROMATIC HYDROCARBONS</subject><subject>CENTRAL NERVOUS SYSTEM</subject><subject>CONNECTIVE TISSUE</subject><subject>Developmental exposure</subject><subject>DIGESTIVE SYSTEM</subject><subject>Environmental Pollutants - pharmacokinetics</subject><subject>ETHERS</subject><subject>Female</subject><subject>FETAL MEMBRANES</subject><subject>Fetus - metabolism</subject><subject>FETUSES</subject><subject>GLANDS</subject><subject>HALOGENATED AROMATIC HYDROCARBONS</subject><subject>Halogenated Diphenyl Ethers</subject><subject>Humans</subject><subject>KIDNEYS</subject><subject>LIVER</subject><subject>Male</subject><subject>MALES</subject><subject>MAMMALS</subject><subject>MAN</subject><subject>Maternal Exposure</subject><subject>Maternal-Fetal Exchange</subject><subject>Medical sciences</subject><subject>MEMBRANES</subject><subject>MEN</subject><subject>Models, Biological</subject><subject>NERVOUS SYSTEM</subject><subject>ORGANIC BROMINE COMPOUNDS</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANIC HALOGEN COMPOUNDS</subject><subject>ORGANIC OXYGEN COMPOUNDS</subject><subject>ORGANS</subject><subject>PBPK</subject><subject>Pharmacokinetics</subject><subject>PHENYL ETHER</subject><subject>PLACENTA</subject><subject>Polybrominated Biphenyls - pharmacokinetics</subject><subject>Polybrominated diphenyl ethers</subject><subject>Pregnancy</subject><subject>PRIMATES</subject><subject>Rat</subject><subject>RATS</subject><subject>Rats, Sprague-Dawley</subject><subject>RODENTS</subject><subject>SIMULATION</subject><subject>Species Specificity</subject><subject>Tissue Distribution</subject><subject>TOXICITY</subject><subject>Toxicology</subject><subject>VERTEBRATES</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF1rFDEUhoModlv9A15IQMSr2eZ7ZsCbWusHFHqjIN6EbHLGZs1Mpkm2uP--GXaxd7068PK8h3MehN5QsqaEqvPtuhgzrxkhfQ3WhPbP0IqSXjWEc_4crQgRtCGk-3WCTnPekgoKQV-iE9p3HVetWKHfF3i-3WcfQ_zjrQlhjzcmg6upSaOx8a-foHiLx-gg4CEm7OAeQpxHmIoJGP7NMe8S4BLxp89XjWixn3AyJb9CLwYTMrw-zjP088vVj8tvzfXN1--XF9eNFUKWprVy6DZOKjCM9oNQwJ0FopyxHKwAJqiVXEruYNg4MI61HW0VF5SAUIrzM_TusDfm4nW2voC9tXGawBbNKBeik7RSHw7UnOLdDnLRo88WQjATxF3WrRAt7RlXlWQH0qaYc4JBz8mPJu01JXoRr7d6Ea8X8UtWxdfS2-P63WYE91g5mq7A-yNgcvU8JDNZn_9zjHHJZNtW7uOBg6rs3kNaPoLJgvNpechF_9QdD9ZuoRs</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Emond, Claude</creator><creator>Raymer, James H.</creator><creator>Studabaker, William B.</creator><creator>Garner, C. 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Edwin ; Birnbaum, Linda S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-7c5f8bd56ea219f46e3dce06dac3ec4e241c53553defbdead2781763410e46633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ADIPOSE TISSUE</topic><topic>ANIMAL TISSUES</topic><topic>ANIMALS</topic><topic>AROMATICS</topic><topic>BDE-47</topic><topic>Biological and medical sciences</topic><topic>BODY</topic><topic>BRAIN</topic><topic>BROMINATED AROMATIC HYDROCARBONS</topic><topic>CENTRAL NERVOUS SYSTEM</topic><topic>CONNECTIVE TISSUE</topic><topic>Developmental exposure</topic><topic>DIGESTIVE SYSTEM</topic><topic>Environmental Pollutants - pharmacokinetics</topic><topic>ETHERS</topic><topic>Female</topic><topic>FETAL MEMBRANES</topic><topic>Fetus - metabolism</topic><topic>FETUSES</topic><topic>GLANDS</topic><topic>HALOGENATED AROMATIC HYDROCARBONS</topic><topic>Halogenated Diphenyl Ethers</topic><topic>Humans</topic><topic>KIDNEYS</topic><topic>LIVER</topic><topic>Male</topic><topic>MALES</topic><topic>MAMMALS</topic><topic>MAN</topic><topic>Maternal Exposure</topic><topic>Maternal-Fetal Exchange</topic><topic>Medical sciences</topic><topic>MEMBRANES</topic><topic>MEN</topic><topic>Models, Biological</topic><topic>NERVOUS SYSTEM</topic><topic>ORGANIC BROMINE COMPOUNDS</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANIC HALOGEN COMPOUNDS</topic><topic>ORGANIC OXYGEN COMPOUNDS</topic><topic>ORGANS</topic><topic>PBPK</topic><topic>Pharmacokinetics</topic><topic>PHENYL ETHER</topic><topic>PLACENTA</topic><topic>Polybrominated Biphenyls - pharmacokinetics</topic><topic>Polybrominated diphenyl ethers</topic><topic>Pregnancy</topic><topic>PRIMATES</topic><topic>Rat</topic><topic>RATS</topic><topic>Rats, Sprague-Dawley</topic><topic>RODENTS</topic><topic>SIMULATION</topic><topic>Species Specificity</topic><topic>Tissue Distribution</topic><topic>TOXICITY</topic><topic>Toxicology</topic><topic>VERTEBRATES</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Emond, Claude</creatorcontrib><creatorcontrib>Raymer, James H.</creatorcontrib><creatorcontrib>Studabaker, William B.</creatorcontrib><creatorcontrib>Garner, C. 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Edwin</au><au>Birnbaum, Linda S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A physiologically based pharmacokinetic model for developmental exposure to BDE-47 in rats</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2010-02-01</date><risdate>2010</risdate><volume>242</volume><issue>3</issue><spage>290</spage><epage>298</epage><pages>290-298</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments, where they have the potential to bioaccumulate in wildlife and humans. Of the 209 possible PBDEs, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) is usually the dominant congener found in human blood and milk samples. BDE-47 has been shown to have endocrine activity and produce developmental, reproductive, and neurotoxic effects. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for BDE-47 in male and female (pregnant and non-pregnant) adult rats to facilitate investigations of developmental exposure. This model consists of eight compartments: liver, brain, adipose tissue, kidney, placenta, fetus, blood, and the rest of the body. Concentrations of BDE-47 from the literature and from maternal–fetal pharmacokinetic studies conducted at RTI International were used to parameterize and evaluate the model. The results showed that the model simulated BDE-47 tissue concentrations in adult male, maternal, and fetal compartments within the standard deviations of the experimental data. The model's ability to estimate BDE-47 concentrations in the fetus after maternal exposure will be useful to design in utero exposure/effect studies. This PBPK model is the first one designed for any PBDE pharmaco/toxicokinetic description. The next steps will be to expand this model to simulate BDE-47 pharmacokinetics and distributions across species (mice), and then extrapolate it to humans. After mouse and human model development, additional PBDE congeners will be incorporated into the model and simulated as a mixture.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>19883674</pmid><doi>10.1016/j.taap.2009.10.019</doi><tpages>9</tpages></addata></record> |
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| ispartof | Toxicology and applied pharmacology, 2010-02, Vol.242 (3), p.290-298 |
| issn | 0041-008X 1096-0333 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 60 APPLIED LIFE SCIENCES ADIPOSE TISSUE ANIMAL TISSUES ANIMALS AROMATICS BDE-47 Biological and medical sciences BODY BRAIN BROMINATED AROMATIC HYDROCARBONS CENTRAL NERVOUS SYSTEM CONNECTIVE TISSUE Developmental exposure DIGESTIVE SYSTEM Environmental Pollutants - pharmacokinetics ETHERS Female FETAL MEMBRANES Fetus - metabolism FETUSES GLANDS HALOGENATED AROMATIC HYDROCARBONS Halogenated Diphenyl Ethers Humans KIDNEYS LIVER Male MALES MAMMALS MAN Maternal Exposure Maternal-Fetal Exchange Medical sciences MEMBRANES MEN Models, Biological NERVOUS SYSTEM ORGANIC BROMINE COMPOUNDS ORGANIC COMPOUNDS ORGANIC HALOGEN COMPOUNDS ORGANIC OXYGEN COMPOUNDS ORGANS PBPK Pharmacokinetics PHENYL ETHER PLACENTA Polybrominated Biphenyls - pharmacokinetics Polybrominated diphenyl ethers Pregnancy PRIMATES Rat RATS Rats, Sprague-Dawley RODENTS SIMULATION Species Specificity Tissue Distribution TOXICITY Toxicology VERTEBRATES |
| title | A physiologically based pharmacokinetic model for developmental exposure to BDE-47 in rats |
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