Inhalation and epidermal exposure of volunteers to ethylene glycol: Kinetics of absorption, urinary excretion, and metabolism to glycolate and oxalate
Ethylene glycol (EG) is a widely used liquid. Limited data are published regarding inhaled EG and no data regarding transdermal EG uptake in humans. In order to gain information on the quantitative fate of EG, four male volunteers inhaled between 1340 and 1610 μmol vaporous 13C-labeled EG ( 13C 2-EG...
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| Veröffentlicht in: | Toxicology letters 2008-05, Vol.178 (2), p.131-141 |
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| creator | Upadhyay, Swapna Carstens, Joern Klein, Dominik Faller, Thomas H. Halbach, Stephan Kirchinger, Werner Kessler, Winfried Csanády, György A. Filser, Johannes G. |
| description | Ethylene glycol (EG) is a widely used liquid. Limited data are published regarding inhaled EG and no data regarding transdermal EG uptake in humans. In order to gain information on the quantitative fate of EG, four male volunteers inhaled between 1340 and 1610
μmol vaporous
13C-labeled EG (
13C
2-EG) for 4
h. Separately, three of these subjects were epidermally exposed for up to 6
h to liquid
13C
2-EG (skin area 66
cm
2). Plasma concentrations and urinary amounts of
13C
2-EG were determined by gas chromatography with mass selective detection. Additionally, plasma was assayed for
13C-labeled glycolic acid (
13C
2-GA) and urine for
13C
2-GA and
13C-labeled oxalic acid (
13C
2-OA). Both EG metabolites were nephrotoxic in animals and humans and embryotoxic in rodents.
13C-labels enabled to differentiate from also determined endogenous EG, glycolic acid (GA), and oxalic acid (OA). Of
13C
2-EG inhaled, 5.5
±
3.0%, 0.77
±
0.15%, and 0.10
±
0.12% were detected in urine as
13C
2-EG,
13C
2-GA, and
13C
2-OA, respectively. The skin permeability constant of liquid EG was 2.7
×
10
−5
±
0.5
×
10
−5
cm/h. Of the dose taken up transdermally, 8.1
±
3.2% and up to 0.4% were excreted in urine as
13C
2-EG and
13C
2-GA, respectively. It is calculated that equally long-lasting exposure to 10
ppm vaporous EG or wetting of both hands by liquid EG leads to about the same body burden by EG and metabolites. The amounts of GA and OA excreted daily in urine as a result of exposure (8
h/day) to 10
ppm EG are about 15% and 2%, respectively, of those excreted from naturally occurring endogenous GA and OA. |
| doi_str_mv | 10.1016/j.toxlet.2008.02.010 |
| format | Article |
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μmol vaporous
13C-labeled EG (
13C
2-EG) for 4
h. Separately, three of these subjects were epidermally exposed for up to 6
h to liquid
13C
2-EG (skin area 66
cm
2). Plasma concentrations and urinary amounts of
13C
2-EG were determined by gas chromatography with mass selective detection. Additionally, plasma was assayed for
13C-labeled glycolic acid (
13C
2-GA) and urine for
13C
2-GA and
13C-labeled oxalic acid (
13C
2-OA). Both EG metabolites were nephrotoxic in animals and humans and embryotoxic in rodents.
13C-labels enabled to differentiate from also determined endogenous EG, glycolic acid (GA), and oxalic acid (OA). Of
13C
2-EG inhaled, 5.5
±
3.0%, 0.77
±
0.15%, and 0.10
±
0.12% were detected in urine as
13C
2-EG,
13C
2-GA, and
13C
2-OA, respectively. The skin permeability constant of liquid EG was 2.7
×
10
−5
±
0.5
×
10
−5
cm/h. Of the dose taken up transdermally, 8.1
±
3.2% and up to 0.4% were excreted in urine as
13C
2-EG and
13C
2-GA, respectively. It is calculated that equally long-lasting exposure to 10
ppm vaporous EG or wetting of both hands by liquid EG leads to about the same body burden by EG and metabolites. The amounts of GA and OA excreted daily in urine as a result of exposure (8
h/day) to 10
ppm EG are about 15% and 2%, respectively, of those excreted from naturally occurring endogenous GA and OA.</description><identifier>ISSN: 0378-4274</identifier><identifier>EISSN: 1879-3169</identifier><identifier>DOI: 10.1016/j.toxlet.2008.02.010</identifier><identifier>PMID: 18430528</identifier><identifier>CODEN: TOLED5</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Administration, Topical ; Adult ; Area Under Curve ; Biological and medical sciences ; Chemical and industrial products toxicology. Toxic occupational diseases ; Chromatography, Gas ; Diffusion ; Epidermal exposure ; Ethylene glycol ; Ethylene Glycol - pharmacokinetics ; Ethylene Glycol - toxicity ; Female ; Glycolates - metabolism ; Glycolates - pharmacokinetics ; Glycolates - urine ; Half-Life ; Health risk ; Human ; Humans ; Inhalation Exposure ; Iodine Radioisotopes ; Kidney - metabolism ; Male ; Medical sciences ; Middle Aged ; Oxalates - metabolism ; Oxalates - pharmacokinetics ; Oxalates - urine ; Permeability constant ; Pharmacokinetics ; Skin Absorption - physiology ; Solvents ; Toxicology</subject><ispartof>Toxicology letters, 2008-05, Vol.178 (2), p.131-141</ispartof><rights>2008 Elsevier Ireland Ltd</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-108c408e1550b0614c7b8c5374cf947f46203cd34f7f9f061e87c2890b3833e53</citedby><cites>FETCH-LOGICAL-c487t-108c408e1550b0614c7b8c5374cf947f46203cd34f7f9f061e87c2890b3833e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.toxlet.2008.02.010$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20325221$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18430528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Upadhyay, Swapna</creatorcontrib><creatorcontrib>Carstens, Joern</creatorcontrib><creatorcontrib>Klein, Dominik</creatorcontrib><creatorcontrib>Faller, Thomas H.</creatorcontrib><creatorcontrib>Halbach, Stephan</creatorcontrib><creatorcontrib>Kirchinger, Werner</creatorcontrib><creatorcontrib>Kessler, Winfried</creatorcontrib><creatorcontrib>Csanády, György A.</creatorcontrib><creatorcontrib>Filser, Johannes G.</creatorcontrib><title>Inhalation and epidermal exposure of volunteers to ethylene glycol: Kinetics of absorption, urinary excretion, and metabolism to glycolate and oxalate</title><title>Toxicology letters</title><addtitle>Toxicol Lett</addtitle><description>Ethylene glycol (EG) is a widely used liquid. Limited data are published regarding inhaled EG and no data regarding transdermal EG uptake in humans. In order to gain information on the quantitative fate of EG, four male volunteers inhaled between 1340 and 1610
μmol vaporous
13C-labeled EG (
13C
2-EG) for 4
h. Separately, three of these subjects were epidermally exposed for up to 6
h to liquid
13C
2-EG (skin area 66
cm
2). Plasma concentrations and urinary amounts of
13C
2-EG were determined by gas chromatography with mass selective detection. Additionally, plasma was assayed for
13C-labeled glycolic acid (
13C
2-GA) and urine for
13C
2-GA and
13C-labeled oxalic acid (
13C
2-OA). Both EG metabolites were nephrotoxic in animals and humans and embryotoxic in rodents.
13C-labels enabled to differentiate from also determined endogenous EG, glycolic acid (GA), and oxalic acid (OA). Of
13C
2-EG inhaled, 5.5
±
3.0%, 0.77
±
0.15%, and 0.10
±
0.12% were detected in urine as
13C
2-EG,
13C
2-GA, and
13C
2-OA, respectively. The skin permeability constant of liquid EG was 2.7
×
10
−5
±
0.5
×
10
−5
cm/h. Of the dose taken up transdermally, 8.1
±
3.2% and up to 0.4% were excreted in urine as
13C
2-EG and
13C
2-GA, respectively. It is calculated that equally long-lasting exposure to 10
ppm vaporous EG or wetting of both hands by liquid EG leads to about the same body burden by EG and metabolites. The amounts of GA and OA excreted daily in urine as a result of exposure (8
h/day) to 10
ppm EG are about 15% and 2%, respectively, of those excreted from naturally occurring endogenous GA and OA.</description><subject>Administration, Topical</subject><subject>Adult</subject><subject>Area Under Curve</subject><subject>Biological and medical sciences</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>Chromatography, Gas</subject><subject>Diffusion</subject><subject>Epidermal exposure</subject><subject>Ethylene glycol</subject><subject>Ethylene Glycol - pharmacokinetics</subject><subject>Ethylene Glycol - toxicity</subject><subject>Female</subject><subject>Glycolates - metabolism</subject><subject>Glycolates - pharmacokinetics</subject><subject>Glycolates - urine</subject><subject>Half-Life</subject><subject>Health risk</subject><subject>Human</subject><subject>Humans</subject><subject>Inhalation Exposure</subject><subject>Iodine Radioisotopes</subject><subject>Kidney - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Oxalates - metabolism</subject><subject>Oxalates - pharmacokinetics</subject><subject>Oxalates - urine</subject><subject>Permeability constant</subject><subject>Pharmacokinetics</subject><subject>Skin Absorption - physiology</subject><subject>Solvents</subject><subject>Toxicology</subject><issn>0378-4274</issn><issn>1879-3169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhSMEotPCGyDkDazIcP2TxGGBhCoKFZXYwNpynBvqkRMH26lmXoTnxSEj2LGyZH_n-Nx7iuIFhT0FWr897JM_Okx7BiD3wPZA4VGxo7JpS07r9nGxA97IUrBGXBSXMR4AoBZ19bS4oFJwqJjcFb9up3vtdLJ-InrqCc62xzBqR_A4-7gEJH4gD94tU0IMkSRPMN2fHE5IfriT8e4d-WInTNbEFdVd9GFe_d6QJdhJh1O2MgG3q_WPEZPuvLNxXN02E53wz5s_rmnwWfFk0C7i8_N5VXy_-fjt-nN59_XT7fWHu9II2aSSgjQCJNKqgg5qKkzTSVPxRpihFc0gagbc9FwMzdAOGUDZGCZb6LjkHCt-VbzefOfgfy4YkxptNOicntAvUTFoWN4rZFBsoAk-xoCDmoMd83CKglr7UAe19aHWPhQwlXVZ9vLsv3Qj9v9E5wIy8OoM6Gi0G4KejI1_uRyfVYzRzL3fOMzbeLAYVDQWJ4O9DWiS6r39f5LffUetlg</recordid><startdate>20080505</startdate><enddate>20080505</enddate><creator>Upadhyay, Swapna</creator><creator>Carstens, Joern</creator><creator>Klein, Dominik</creator><creator>Faller, Thomas H.</creator><creator>Halbach, Stephan</creator><creator>Kirchinger, Werner</creator><creator>Kessler, Winfried</creator><creator>Csanády, György A.</creator><creator>Filser, Johannes G.</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Science</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></search><sort><creationdate>20080505</creationdate><title>Inhalation and epidermal exposure of volunteers to ethylene glycol: Kinetics of absorption, urinary excretion, and metabolism to glycolate and oxalate</title><author>Upadhyay, Swapna ; Carstens, Joern ; Klein, Dominik ; Faller, Thomas H. ; Halbach, Stephan ; Kirchinger, Werner ; Kessler, Winfried ; Csanády, György A. ; Filser, Johannes G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-108c408e1550b0614c7b8c5374cf947f46203cd34f7f9f061e87c2890b3833e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Administration, Topical</topic><topic>Adult</topic><topic>Area Under Curve</topic><topic>Biological and medical sciences</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>Chromatography, Gas</topic><topic>Diffusion</topic><topic>Epidermal exposure</topic><topic>Ethylene glycol</topic><topic>Ethylene Glycol - pharmacokinetics</topic><topic>Ethylene Glycol - toxicity</topic><topic>Female</topic><topic>Glycolates - metabolism</topic><topic>Glycolates - pharmacokinetics</topic><topic>Glycolates - urine</topic><topic>Half-Life</topic><topic>Health risk</topic><topic>Human</topic><topic>Humans</topic><topic>Inhalation Exposure</topic><topic>Iodine Radioisotopes</topic><topic>Kidney - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Oxalates - metabolism</topic><topic>Oxalates - pharmacokinetics</topic><topic>Oxalates - urine</topic><topic>Permeability constant</topic><topic>Pharmacokinetics</topic><topic>Skin Absorption - physiology</topic><topic>Solvents</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Upadhyay, Swapna</creatorcontrib><creatorcontrib>Carstens, Joern</creatorcontrib><creatorcontrib>Klein, Dominik</creatorcontrib><creatorcontrib>Faller, Thomas H.</creatorcontrib><creatorcontrib>Halbach, Stephan</creatorcontrib><creatorcontrib>Kirchinger, Werner</creatorcontrib><creatorcontrib>Kessler, Winfried</creatorcontrib><creatorcontrib>Csanády, György A.</creatorcontrib><creatorcontrib>Filser, Johannes 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><jtitle>Toxicology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Upadhyay, Swapna</au><au>Carstens, Joern</au><au>Klein, Dominik</au><au>Faller, Thomas H.</au><au>Halbach, Stephan</au><au>Kirchinger, Werner</au><au>Kessler, Winfried</au><au>Csanády, György A.</au><au>Filser, Johannes G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhalation and epidermal exposure of volunteers to ethylene glycol: Kinetics of absorption, urinary excretion, and metabolism to glycolate and oxalate</atitle><jtitle>Toxicology letters</jtitle><addtitle>Toxicol Lett</addtitle><date>2008-05-05</date><risdate>2008</risdate><volume>178</volume><issue>2</issue><spage>131</spage><epage>141</epage><pages>131-141</pages><issn>0378-4274</issn><eissn>1879-3169</eissn><coden>TOLED5</coden><abstract>Ethylene glycol (EG) is a widely used liquid. Limited data are published regarding inhaled EG and no data regarding transdermal EG uptake in humans. In order to gain information on the quantitative fate of EG, four male volunteers inhaled between 1340 and 1610
μmol vaporous
13C-labeled EG (
13C
2-EG) for 4
h. Separately, three of these subjects were epidermally exposed for up to 6
h to liquid
13C
2-EG (skin area 66
cm
2). Plasma concentrations and urinary amounts of
13C
2-EG were determined by gas chromatography with mass selective detection. Additionally, plasma was assayed for
13C-labeled glycolic acid (
13C
2-GA) and urine for
13C
2-GA and
13C-labeled oxalic acid (
13C
2-OA). Both EG metabolites were nephrotoxic in animals and humans and embryotoxic in rodents.
13C-labels enabled to differentiate from also determined endogenous EG, glycolic acid (GA), and oxalic acid (OA). Of
13C
2-EG inhaled, 5.5
±
3.0%, 0.77
±
0.15%, and 0.10
±
0.12% were detected in urine as
13C
2-EG,
13C
2-GA, and
13C
2-OA, respectively. The skin permeability constant of liquid EG was 2.7
×
10
−5
±
0.5
×
10
−5
cm/h. Of the dose taken up transdermally, 8.1
±
3.2% and up to 0.4% were excreted in urine as
13C
2-EG and
13C
2-GA, respectively. It is calculated that equally long-lasting exposure to 10
ppm vaporous EG or wetting of both hands by liquid EG leads to about the same body burden by EG and metabolites. The amounts of GA and OA excreted daily in urine as a result of exposure (8
h/day) to 10
ppm EG are about 15% and 2%, respectively, of those excreted from naturally occurring endogenous GA and OA.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>18430528</pmid><doi>10.1016/j.toxlet.2008.02.010</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0378-4274 |
| ispartof | Toxicology letters, 2008-05, Vol.178 (2), p.131-141 |
| issn | 0378-4274 1879-3169 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_20720100 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Administration, Topical Adult Area Under Curve Biological and medical sciences Chemical and industrial products toxicology. Toxic occupational diseases Chromatography, Gas Diffusion Epidermal exposure Ethylene glycol Ethylene Glycol - pharmacokinetics Ethylene Glycol - toxicity Female Glycolates - metabolism Glycolates - pharmacokinetics Glycolates - urine Half-Life Health risk Human Humans Inhalation Exposure Iodine Radioisotopes Kidney - metabolism Male Medical sciences Middle Aged Oxalates - metabolism Oxalates - pharmacokinetics Oxalates - urine Permeability constant Pharmacokinetics Skin Absorption - physiology Solvents Toxicology |
| title | Inhalation and epidermal exposure of volunteers to ethylene glycol: Kinetics of absorption, urinary excretion, and metabolism to glycolate and oxalate |
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