Inhalation pharmacokinetics of 1,2-epoxybutene-3 reveal species differences between rats and mice sensitive to butadiene-induced carcinogenesis
Comparative investigations of inhalation pharmacokinetics of 1,2-epoxybutene-3 (vinyl oxirane, the primary reactive intermediate of butadiene) revealed major differences in metabolism of this compound between rats and mice. Whereas in rats no indication of saturation kinetics of epoxybutene metaboli...
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Veröffentlicht in: | Archives of toxicology 1987-10, Vol.61 (1), p.7-11 |
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description | Comparative investigations of inhalation pharmacokinetics of 1,2-epoxybutene-3 (vinyl oxirane, the primary reactive intermediate of butadiene) revealed major differences in metabolism of this compound between rats and mice. Whereas in rats no indication of saturation kinetics of epoxybutene metabolism could be observed up to exposure concentrations of 5000 ppm, in mice saturation of epoxybutene metabolism becomes apparent at atmospheric concentrations of about 500 ppm. The estimated maximal metabolic rate (Vmax) in mice for epoxybutene was only 350 mumol X h-1 X kg-1 (rats: greater than 2600 mumol X h-1 X kg-1). In the lower concentration range where first order metabolism applies (up to about 500 ppm) epoxybutene is metabolized by mice at higher rates compared to rats (metabolic clearance per kg body weight, mice: 24,900 ml X h-1, rats: 13,400 ml X h-1). Under these conditions the steady state concentration of epoxybutene in the mouse is about 10 times that in the rat. When mice are exposed to high concentrations of butadiene (greater than 2000 ppm; conditions of saturation of butadiene metabolism; closed exposure system) epoxybutene is exhaled by the animals, and its concentration in the gas phase increases with exposure time. At about 10 ppm epoxybutene signs of acute toxicity are observed. When rats are exposed to butadiene under similar conditions, the epoxybutene concentration reaches a plateau at about 4 ppm. Under these conditions hepatic non-protein sulfhydryl compounds are virtually depleted in mice but not in rats. |
doi_str_mv | 10.1007/BF00324541 |
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J ; FILSER, J. G ; BOLT, H. M</creator><creatorcontrib>KREILING, R ; LAIB, R. J ; FILSER, J. G ; BOLT, H. M</creatorcontrib><description>Comparative investigations of inhalation pharmacokinetics of 1,2-epoxybutene-3 (vinyl oxirane, the primary reactive intermediate of butadiene) revealed major differences in metabolism of this compound between rats and mice. Whereas in rats no indication of saturation kinetics of epoxybutene metabolism could be observed up to exposure concentrations of 5000 ppm, in mice saturation of epoxybutene metabolism becomes apparent at atmospheric concentrations of about 500 ppm. The estimated maximal metabolic rate (Vmax) in mice for epoxybutene was only 350 mumol X h-1 X kg-1 (rats: greater than 2600 mumol X h-1 X kg-1). In the lower concentration range where first order metabolism applies (up to about 500 ppm) epoxybutene is metabolized by mice at higher rates compared to rats (metabolic clearance per kg body weight, mice: 24,900 ml X h-1, rats: 13,400 ml X h-1). Under these conditions the steady state concentration of epoxybutene in the mouse is about 10 times that in the rat. When mice are exposed to high concentrations of butadiene (greater than 2000 ppm; conditions of saturation of butadiene metabolism; closed exposure system) epoxybutene is exhaled by the animals, and its concentration in the gas phase increases with exposure time. At about 10 ppm epoxybutene signs of acute toxicity are observed. When rats are exposed to butadiene under similar conditions, the epoxybutene concentration reaches a plateau at about 4 ppm. Under these conditions hepatic non-protein sulfhydryl compounds are virtually depleted in mice but not in rats.</description><identifier>ISSN: 0340-5761</identifier><identifier>EISSN: 1432-0738</identifier><identifier>DOI: 10.1007/BF00324541</identifier><identifier>PMID: 3439877</identifier><identifier>CODEN: ARTODN</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Administration, Inhalation ; Animals ; Biological and medical sciences ; Butadienes - pharmacokinetics ; Butadienes - toxicity ; Carcinogenesis, carcinogens and anticarcinogens ; Carcinogens - pharmacokinetics ; Chemical agents ; Chromatography, Gas ; Epoxy Compounds - pharmacokinetics ; Ethers, Cyclic - pharmacokinetics ; Glutathione - metabolism ; Liver - metabolism ; Medical sciences ; Mice ; Mice, Inbred Strains ; Rats ; Rats, Inbred Strains ; Species Specificity ; Tumors</subject><ispartof>Archives of toxicology, 1987-10, Vol.61 (1), p.7-11</ispartof><rights>1988 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c311t-ff50a63027d1ba6f5954b8d6901384cc5d6e969ccdf4fac38e2d8bd74bd895063</citedby><cites>FETCH-LOGICAL-c311t-ff50a63027d1ba6f5954b8d6901384cc5d6e969ccdf4fac38e2d8bd74bd895063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7621367$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3439877$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KREILING, R</creatorcontrib><creatorcontrib>LAIB, R. J</creatorcontrib><creatorcontrib>FILSER, J. G</creatorcontrib><creatorcontrib>BOLT, H. M</creatorcontrib><title>Inhalation pharmacokinetics of 1,2-epoxybutene-3 reveal species differences between rats and mice sensitive to butadiene-induced carcinogenesis</title><title>Archives of toxicology</title><addtitle>Arch Toxicol</addtitle><description>Comparative investigations of inhalation pharmacokinetics of 1,2-epoxybutene-3 (vinyl oxirane, the primary reactive intermediate of butadiene) revealed major differences in metabolism of this compound between rats and mice. Whereas in rats no indication of saturation kinetics of epoxybutene metabolism could be observed up to exposure concentrations of 5000 ppm, in mice saturation of epoxybutene metabolism becomes apparent at atmospheric concentrations of about 500 ppm. The estimated maximal metabolic rate (Vmax) in mice for epoxybutene was only 350 mumol X h-1 X kg-1 (rats: greater than 2600 mumol X h-1 X kg-1). In the lower concentration range where first order metabolism applies (up to about 500 ppm) epoxybutene is metabolized by mice at higher rates compared to rats (metabolic clearance per kg body weight, mice: 24,900 ml X h-1, rats: 13,400 ml X h-1). Under these conditions the steady state concentration of epoxybutene in the mouse is about 10 times that in the rat. When mice are exposed to high concentrations of butadiene (greater than 2000 ppm; conditions of saturation of butadiene metabolism; closed exposure system) epoxybutene is exhaled by the animals, and its concentration in the gas phase increases with exposure time. At about 10 ppm epoxybutene signs of acute toxicity are observed. When rats are exposed to butadiene under similar conditions, the epoxybutene concentration reaches a plateau at about 4 ppm. Under these conditions hepatic non-protein sulfhydryl compounds are virtually depleted in mice but not in rats.</description><subject>Administration, Inhalation</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Butadienes - pharmacokinetics</subject><subject>Butadienes - toxicity</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>Carcinogens - pharmacokinetics</subject><subject>Chemical agents</subject><subject>Chromatography, Gas</subject><subject>Epoxy Compounds - pharmacokinetics</subject><subject>Ethers, Cyclic - pharmacokinetics</subject><subject>Glutathione - metabolism</subject><subject>Liver - metabolism</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Species Specificity</subject><subject>Tumors</subject><issn>0340-5761</issn><issn>1432-0738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1987</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkLtOxDAQRS0EguXR0CO5oEIE7NixkxIQj5VWooF6NRmPwbDrRHaWx1fwywSxgmqu5h6d4jJ2KMWZFMKeX94IoUpdabnBJlKrshBW1ZtsIpQWRWWN3GG7Ob8IIcu6UdtsW2nV1NZO2Nc0PsMChtBF3j9DWgJ2ryHSEDDzznN5WhbUdx-f7WqgSIXiid4IFjz3hIEyd8F7ShRxzC0N70SRJxgyh-j4MiDxTDGHIbwRHzo-asCFH1OIboXkOELCELun8ZdD3mdbHhaZDtZ3jz3eXD9c3RWz-9vp1cWsQCXlUHhfCTBKlNbJFoyvmkq3tTONkKrWiJUz1JgG0XntAVVNpatbZ3Xr6qYSRu2xk18vpi7nRH7ep7CE9DmXYv4z6vx_1BE--oX7Vbsk94euVxz743UPGWHhE0QM-Q-zppTKWPUNeLyBdQ</recordid><startdate>19871001</startdate><enddate>19871001</enddate><creator>KREILING, R</creator><creator>LAIB, R. J</creator><creator>FILSER, J. G</creator><creator>BOLT, H. M</creator><general>Springer</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></search><sort><creationdate>19871001</creationdate><title>Inhalation pharmacokinetics of 1,2-epoxybutene-3 reveal species differences between rats and mice sensitive to butadiene-induced carcinogenesis</title><author>KREILING, R ; LAIB, R. J ; FILSER, J. G ; BOLT, H. M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c311t-ff50a63027d1ba6f5954b8d6901384cc5d6e969ccdf4fac38e2d8bd74bd895063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1987</creationdate><topic>Administration, Inhalation</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Butadienes - pharmacokinetics</topic><topic>Butadienes - toxicity</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>Carcinogens - pharmacokinetics</topic><topic>Chemical agents</topic><topic>Chromatography, Gas</topic><topic>Epoxy Compounds - pharmacokinetics</topic><topic>Ethers, Cyclic - pharmacokinetics</topic><topic>Glutathione - metabolism</topic><topic>Liver - metabolism</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Species Specificity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KREILING, R</creatorcontrib><creatorcontrib>LAIB, R. J</creatorcontrib><creatorcontrib>FILSER, J. G</creatorcontrib><creatorcontrib>BOLT, H. M</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><jtitle>Archives of toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KREILING, R</au><au>LAIB, R. J</au><au>FILSER, J. G</au><au>BOLT, H. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhalation pharmacokinetics of 1,2-epoxybutene-3 reveal species differences between rats and mice sensitive to butadiene-induced carcinogenesis</atitle><jtitle>Archives of toxicology</jtitle><addtitle>Arch Toxicol</addtitle><date>1987-10-01</date><risdate>1987</risdate><volume>61</volume><issue>1</issue><spage>7</spage><epage>11</epage><pages>7-11</pages><issn>0340-5761</issn><eissn>1432-0738</eissn><coden>ARTODN</coden><abstract>Comparative investigations of inhalation pharmacokinetics of 1,2-epoxybutene-3 (vinyl oxirane, the primary reactive intermediate of butadiene) revealed major differences in metabolism of this compound between rats and mice. Whereas in rats no indication of saturation kinetics of epoxybutene metabolism could be observed up to exposure concentrations of 5000 ppm, in mice saturation of epoxybutene metabolism becomes apparent at atmospheric concentrations of about 500 ppm. The estimated maximal metabolic rate (Vmax) in mice for epoxybutene was only 350 mumol X h-1 X kg-1 (rats: greater than 2600 mumol X h-1 X kg-1). In the lower concentration range where first order metabolism applies (up to about 500 ppm) epoxybutene is metabolized by mice at higher rates compared to rats (metabolic clearance per kg body weight, mice: 24,900 ml X h-1, rats: 13,400 ml X h-1). Under these conditions the steady state concentration of epoxybutene in the mouse is about 10 times that in the rat. When mice are exposed to high concentrations of butadiene (greater than 2000 ppm; conditions of saturation of butadiene metabolism; closed exposure system) epoxybutene is exhaled by the animals, and its concentration in the gas phase increases with exposure time. At about 10 ppm epoxybutene signs of acute toxicity are observed. When rats are exposed to butadiene under similar conditions, the epoxybutene concentration reaches a plateau at about 4 ppm. Under these conditions hepatic non-protein sulfhydryl compounds are virtually depleted in mice but not in rats.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>3439877</pmid><doi>10.1007/BF00324541</doi><tpages>5</tpages></addata></record> |
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subjects | Administration, Inhalation Animals Biological and medical sciences Butadienes - pharmacokinetics Butadienes - toxicity Carcinogenesis, carcinogens and anticarcinogens Carcinogens - pharmacokinetics Chemical agents Chromatography, Gas Epoxy Compounds - pharmacokinetics Ethers, Cyclic - pharmacokinetics Glutathione - metabolism Liver - metabolism Medical sciences Mice Mice, Inbred Strains Rats Rats, Inbred Strains Species Specificity Tumors |
title | Inhalation pharmacokinetics of 1,2-epoxybutene-3 reveal species differences between rats and mice sensitive to butadiene-induced carcinogenesis |
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