Metabolism and disposition of ethylene carbonate in male Fischer 344 rats
Ethylene carbonate (EC) has a toxicity profile which resembles that of ethylene glycol (EG). To determine whether the toxicity of EC could be explained on the basis of its metabolism to EG, male Fischer 344 rats were given 200 mg/kg of uniformly labeled [ 14C]EC in water by gavage and the dispositio...
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| Veröffentlicht in: | Toxicology and applied pharmacology 1989-08, Vol.100 (1), p.24-31 |
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| creator | Hanley, T.R. Schumann, A.M. Langvardt, P.W. Rusek, T.F. Watanabe, P.G. |
| description | Ethylene carbonate (EC) has a toxicity profile which resembles that of ethylene glycol (EG). To determine whether the toxicity of EC could be explained on the basis of its metabolism to EG, male Fischer 344 rats were given 200 mg/kg of uniformly labeled [
14C]EC in water by gavage and the disposition of the radiolabel was then followed for 72 hr. EC was rapidly metabolized, with approximately 57 and 27% of the administered dose eliminated in the expired air as
14CO
2 and in the urine, respectively; the remainder was found in the carcass. Separation of the urinary metabolites using liquid chromatography revealed a single radioactive peak. This metabolite was unequivocally identified as ethylene glycol via gas chromatography-mass spectrometry with the aid of
13C enrichment of the EC dose. Measurement of whole blood levels of EC and EG in rats given 200 mg/kg of EC by gavage revealed blood levels of EG approximately 100-fold higher than the levels of EC in these same animals, with a half-life of EG in blood of 2 hr, indicating rapid conversion of EC to EG. In a separate group of animals administered an equimolar dose of [
14C]EG (141 mg/kg), approximately 37% of the dose was expired as
14CO
2 and 42% was excreted in the urine as parent compound. When expressed on the basis of the ethanediol moiety, the disposition of EC was identical to that of EG. In view of the rapid and extensive biotransformation of EC to EG and the similarity of the existing (though limited) toxicity data base of EC compared to EG, utilization of the extensive EG systemic toxicity data base for assessing the safety of EC appears justified. |
| doi_str_mv | 10.1016/0041-008X(89)90088-4 |
| format | Article |
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14C]EC in water by gavage and the disposition of the radiolabel was then followed for 72 hr. EC was rapidly metabolized, with approximately 57 and 27% of the administered dose eliminated in the expired air as
14CO
2 and in the urine, respectively; the remainder was found in the carcass. Separation of the urinary metabolites using liquid chromatography revealed a single radioactive peak. This metabolite was unequivocally identified as ethylene glycol via gas chromatography-mass spectrometry with the aid of
13C enrichment of the EC dose. Measurement of whole blood levels of EC and EG in rats given 200 mg/kg of EC by gavage revealed blood levels of EG approximately 100-fold higher than the levels of EC in these same animals, with a half-life of EG in blood of 2 hr, indicating rapid conversion of EC to EG. In a separate group of animals administered an equimolar dose of [
14C]EG (141 mg/kg), approximately 37% of the dose was expired as
14CO
2 and 42% was excreted in the urine as parent compound. When expressed on the basis of the ethanediol moiety, the disposition of EC was identical to that of EG. In view of the rapid and extensive biotransformation of EC to EG and the similarity of the existing (though limited) toxicity data base of EC compared to EG, utilization of the extensive EG systemic toxicity data base for assessing the safety of EC appears justified.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/0041-008X(89)90088-4</identifier><identifier>PMID: 2763299</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>550501 - Metabolism- Tracer Techniques ; 560300 - Chemicals Metabolism & Toxicology ; Administration, Oral ; ALCOHOLS ; ALKENES ; Animals ; BASIC BIOLOGICAL SCIENCES ; Biological and medical sciences ; BIOLOGICAL HALF-LIFE ; BIOLOGICAL MATERIALS ; Biotransformation ; BLOOD ; BODY FLUIDS ; CARBON 13 ; CARBON 14 COMPOUNDS ; CARBON COMPOUNDS ; CARBON ISOTOPES ; Carbon Radioisotopes ; CARBONATES ; Chemical and industrial products toxicology. Toxic occupational diseases ; CHROMATOGRAPHY ; Chromatography, High Pressure Liquid ; Dioxolanes - metabolism ; Dioxolanes - pharmacokinetics ; Dioxoles - metabolism ; ETHYLENE ; Ethylene Glycol ; Ethylene Glycols - urine ; EVEN-ODD NUCLEI ; GAS CHROMATOGRAPHY ; GLYCOLS ; HYDROCARBONS ; Hydrolysis ; HYDROXY COMPOUNDS ; ISOTOPE APPLICATIONS ; ISOTOPES ; LABELLED COMPOUNDS ; LIGHT NUCLEI ; LIQUID COLUMN CHROMATOGRAPHY ; Male ; MASS SPECTROSCOPY ; MATERIALS ; Medical sciences ; METABOLISM ; METABOLITES ; NUCLEI ; ORAL ADMINISTRATION ; ORGANIC COMPOUNDS ; OXYGEN COMPOUNDS ; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT ; Rats ; Rats, Inbred F344 ; SEPARATION PROCESSES ; SPECTROSCOPY ; STABLE ISOTOPES ; TOXICITY ; Toxicology ; TRACER TECHNIQUES ; Various organic compounds</subject><ispartof>Toxicology and applied pharmacology, 1989-08, Vol.100 (1), p.24-31</ispartof><rights>1989</rights><rights>1990 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-bdff05b86e49e3bd2ec33a9b063240248ad5948230b23bae4d45a991b14fd5e03</citedby><cites>FETCH-LOGICAL-c444t-bdff05b86e49e3bd2ec33a9b063240248ad5948230b23bae4d45a991b14fd5e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0041008X89900884$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=6811995$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2763299$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/5599411$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Hanley, T.R.</creatorcontrib><creatorcontrib>Schumann, A.M.</creatorcontrib><creatorcontrib>Langvardt, P.W.</creatorcontrib><creatorcontrib>Rusek, T.F.</creatorcontrib><creatorcontrib>Watanabe, P.G.</creatorcontrib><title>Metabolism and disposition of ethylene carbonate in male Fischer 344 rats</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Ethylene carbonate (EC) has a toxicity profile which resembles that of ethylene glycol (EG). To determine whether the toxicity of EC could be explained on the basis of its metabolism to EG, male Fischer 344 rats were given 200 mg/kg of uniformly labeled [
14C]EC in water by gavage and the disposition of the radiolabel was then followed for 72 hr. EC was rapidly metabolized, with approximately 57 and 27% of the administered dose eliminated in the expired air as
14CO
2 and in the urine, respectively; the remainder was found in the carcass. Separation of the urinary metabolites using liquid chromatography revealed a single radioactive peak. This metabolite was unequivocally identified as ethylene glycol via gas chromatography-mass spectrometry with the aid of
13C enrichment of the EC dose. Measurement of whole blood levels of EC and EG in rats given 200 mg/kg of EC by gavage revealed blood levels of EG approximately 100-fold higher than the levels of EC in these same animals, with a half-life of EG in blood of 2 hr, indicating rapid conversion of EC to EG. In a separate group of animals administered an equimolar dose of [
14C]EG (141 mg/kg), approximately 37% of the dose was expired as
14CO
2 and 42% was excreted in the urine as parent compound. When expressed on the basis of the ethanediol moiety, the disposition of EC was identical to that of EG. In view of the rapid and extensive biotransformation of EC to EG and the similarity of the existing (though limited) toxicity data base of EC compared to EG, utilization of the extensive EG systemic toxicity data base for assessing the safety of EC appears justified.</description><subject>550501 - Metabolism- Tracer Techniques</subject><subject>560300 - Chemicals Metabolism & Toxicology</subject><subject>Administration, Oral</subject><subject>ALCOHOLS</subject><subject>ALKENES</subject><subject>Animals</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Biological and medical sciences</subject><subject>BIOLOGICAL HALF-LIFE</subject><subject>BIOLOGICAL MATERIALS</subject><subject>Biotransformation</subject><subject>BLOOD</subject><subject>BODY FLUIDS</subject><subject>CARBON 13</subject><subject>CARBON 14 COMPOUNDS</subject><subject>CARBON COMPOUNDS</subject><subject>CARBON ISOTOPES</subject><subject>Carbon Radioisotopes</subject><subject>CARBONATES</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>CHROMATOGRAPHY</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Dioxolanes - metabolism</subject><subject>Dioxolanes - pharmacokinetics</subject><subject>Dioxoles - metabolism</subject><subject>ETHYLENE</subject><subject>Ethylene Glycol</subject><subject>Ethylene Glycols - urine</subject><subject>EVEN-ODD NUCLEI</subject><subject>GAS CHROMATOGRAPHY</subject><subject>GLYCOLS</subject><subject>HYDROCARBONS</subject><subject>Hydrolysis</subject><subject>HYDROXY COMPOUNDS</subject><subject>ISOTOPE APPLICATIONS</subject><subject>ISOTOPES</subject><subject>LABELLED COMPOUNDS</subject><subject>LIGHT NUCLEI</subject><subject>LIQUID COLUMN CHROMATOGRAPHY</subject><subject>Male</subject><subject>MASS SPECTROSCOPY</subject><subject>MATERIALS</subject><subject>Medical sciences</subject><subject>METABOLISM</subject><subject>METABOLITES</subject><subject>NUCLEI</subject><subject>ORAL ADMINISTRATION</subject><subject>ORGANIC COMPOUNDS</subject><subject>OXYGEN COMPOUNDS</subject><subject>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>SEPARATION PROCESSES</subject><subject>SPECTROSCOPY</subject><subject>STABLE ISOTOPES</subject><subject>TOXICITY</subject><subject>Toxicology</subject><subject>TRACER TECHNIQUES</subject><subject>Various organic compounds</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2LFDEQhoMo67j6DxSCiLiH1qRT3ZtcBFlcd2FlLwreQj6qmUh3MiaZhf33pp1hjp6qoJ4q3noIec3ZR874-Ikx4B1j8tcHqS5Ua2QHT8iGMzV2TAjxlGxOyHPyopTfjDEFwM_IWX85il6pDbn9jtXYNIeyUBM99aHsUgk1pEjTRLFuH2eMSJ3JNkVTkYZIFzMjvQ7FbTFTAUCzqeUleTaZueCrYz0nP6-__ri66e7uv91efbnrHADUzvppYoOVI4JCYX2PTgijLGuBgPUgjR8UyF4w2wtrEDwMRiluOUx-QCbOydvD3VRq0MWFim7rUozoqh4GpYDzBr0_QLuc_uyxVL20uDjPJmLaF82HFgbkZQPhALqcSsk46V0Oi8mPmjO9atarQ7061FLpf5o1tLU3x_t7u6A_LR29tvm749wUZ-Ypm-hCOWGj5FypoWGfDxg2YQ8B8_oPRoc-5PUdn8L_c_wFjgKXmA</recordid><startdate>19890801</startdate><enddate>19890801</enddate><creator>Hanley, T.R.</creator><creator>Schumann, A.M.</creator><creator>Langvardt, P.W.</creator><creator>Rusek, T.F.</creator><creator>Watanabe, P.G.</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>7U7</scope><scope>C1K</scope><scope>OTOTI</scope></search><sort><creationdate>19890801</creationdate><title>Metabolism and disposition of ethylene carbonate in male Fischer 344 rats</title><author>Hanley, T.R. ; Schumann, A.M. ; Langvardt, P.W. ; Rusek, T.F. ; Watanabe, P.G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-bdff05b86e49e3bd2ec33a9b063240248ad5948230b23bae4d45a991b14fd5e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1989</creationdate><topic>550501 - Metabolism- Tracer Techniques</topic><topic>560300 - Chemicals Metabolism & Toxicology</topic><topic>Administration, Oral</topic><topic>ALCOHOLS</topic><topic>ALKENES</topic><topic>Animals</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Biological and medical sciences</topic><topic>BIOLOGICAL HALF-LIFE</topic><topic>BIOLOGICAL MATERIALS</topic><topic>Biotransformation</topic><topic>BLOOD</topic><topic>BODY FLUIDS</topic><topic>CARBON 13</topic><topic>CARBON 14 COMPOUNDS</topic><topic>CARBON COMPOUNDS</topic><topic>CARBON ISOTOPES</topic><topic>Carbon Radioisotopes</topic><topic>CARBONATES</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>CHROMATOGRAPHY</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Dioxolanes - metabolism</topic><topic>Dioxolanes - pharmacokinetics</topic><topic>Dioxoles - metabolism</topic><topic>ETHYLENE</topic><topic>Ethylene Glycol</topic><topic>Ethylene Glycols - urine</topic><topic>EVEN-ODD NUCLEI</topic><topic>GAS CHROMATOGRAPHY</topic><topic>GLYCOLS</topic><topic>HYDROCARBONS</topic><topic>Hydrolysis</topic><topic>HYDROXY COMPOUNDS</topic><topic>ISOTOPE APPLICATIONS</topic><topic>ISOTOPES</topic><topic>LABELLED COMPOUNDS</topic><topic>LIGHT NUCLEI</topic><topic>LIQUID COLUMN CHROMATOGRAPHY</topic><topic>Male</topic><topic>MASS SPECTROSCOPY</topic><topic>MATERIALS</topic><topic>Medical sciences</topic><topic>METABOLISM</topic><topic>METABOLITES</topic><topic>NUCLEI</topic><topic>ORAL ADMINISTRATION</topic><topic>ORGANIC COMPOUNDS</topic><topic>OXYGEN COMPOUNDS</topic><topic>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>SEPARATION PROCESSES</topic><topic>SPECTROSCOPY</topic><topic>STABLE ISOTOPES</topic><topic>TOXICITY</topic><topic>Toxicology</topic><topic>TRACER TECHNIQUES</topic><topic>Various organic compounds</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hanley, T.R.</creatorcontrib><creatorcontrib>Schumann, A.M.</creatorcontrib><creatorcontrib>Langvardt, P.W.</creatorcontrib><creatorcontrib>Rusek, T.F.</creatorcontrib><creatorcontrib>Watanabe, P.G.</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hanley, T.R.</au><au>Schumann, A.M.</au><au>Langvardt, P.W.</au><au>Rusek, T.F.</au><au>Watanabe, P.G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolism and disposition of ethylene carbonate in male Fischer 344 rats</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>1989-08-01</date><risdate>1989</risdate><volume>100</volume><issue>1</issue><spage>24</spage><epage>31</epage><pages>24-31</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>Ethylene carbonate (EC) has a toxicity profile which resembles that of ethylene glycol (EG). To determine whether the toxicity of EC could be explained on the basis of its metabolism to EG, male Fischer 344 rats were given 200 mg/kg of uniformly labeled [
14C]EC in water by gavage and the disposition of the radiolabel was then followed for 72 hr. EC was rapidly metabolized, with approximately 57 and 27% of the administered dose eliminated in the expired air as
14CO
2 and in the urine, respectively; the remainder was found in the carcass. Separation of the urinary metabolites using liquid chromatography revealed a single radioactive peak. This metabolite was unequivocally identified as ethylene glycol via gas chromatography-mass spectrometry with the aid of
13C enrichment of the EC dose. Measurement of whole blood levels of EC and EG in rats given 200 mg/kg of EC by gavage revealed blood levels of EG approximately 100-fold higher than the levels of EC in these same animals, with a half-life of EG in blood of 2 hr, indicating rapid conversion of EC to EG. In a separate group of animals administered an equimolar dose of [
14C]EG (141 mg/kg), approximately 37% of the dose was expired as
14CO
2 and 42% was excreted in the urine as parent compound. When expressed on the basis of the ethanediol moiety, the disposition of EC was identical to that of EG. In view of the rapid and extensive biotransformation of EC to EG and the similarity of the existing (though limited) toxicity data base of EC compared to EG, utilization of the extensive EG systemic toxicity data base for assessing the safety of EC appears justified.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>2763299</pmid><doi>10.1016/0041-008X(89)90088-4</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0041-008X |
| ispartof | Toxicology and applied pharmacology, 1989-08, Vol.100 (1), p.24-31 |
| issn | 0041-008X 1096-0333 |
| language | eng |
| recordid | cdi_osti_scitechconnect_5599411 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 550501 - Metabolism- Tracer Techniques 560300 - Chemicals Metabolism & Toxicology Administration, Oral ALCOHOLS ALKENES Animals BASIC BIOLOGICAL SCIENCES Biological and medical sciences BIOLOGICAL HALF-LIFE BIOLOGICAL MATERIALS Biotransformation BLOOD BODY FLUIDS CARBON 13 CARBON 14 COMPOUNDS CARBON COMPOUNDS CARBON ISOTOPES Carbon Radioisotopes CARBONATES Chemical and industrial products toxicology. Toxic occupational diseases CHROMATOGRAPHY Chromatography, High Pressure Liquid Dioxolanes - metabolism Dioxolanes - pharmacokinetics Dioxoles - metabolism ETHYLENE Ethylene Glycol Ethylene Glycols - urine EVEN-ODD NUCLEI GAS CHROMATOGRAPHY GLYCOLS HYDROCARBONS Hydrolysis HYDROXY COMPOUNDS ISOTOPE APPLICATIONS ISOTOPES LABELLED COMPOUNDS LIGHT NUCLEI LIQUID COLUMN CHROMATOGRAPHY Male MASS SPECTROSCOPY MATERIALS Medical sciences METABOLISM METABOLITES NUCLEI ORAL ADMINISTRATION ORGANIC COMPOUNDS OXYGEN COMPOUNDS RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT Rats Rats, Inbred F344 SEPARATION PROCESSES SPECTROSCOPY STABLE ISOTOPES TOXICITY Toxicology TRACER TECHNIQUES Various organic compounds |
| title | Metabolism and disposition of ethylene carbonate in male Fischer 344 rats |
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