{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:04:35Z","timestamp":1790593475273,"version":"4.1.0"},"reference-count":50,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2015,9,25]],"date-time":"2015-09-25T00:00:00Z","timestamp":1443139200000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["HHSN29120077563"],"award-info":[{"award-number":["HHSN29120077563"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["N01-ES-75563"],"award-info":[{"award-number":["N01-ES-75563"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The observed toxicity and carcinogenicity of 1,3-dichloro-2-propanol (DCP) in rodents is thought to be due to the formation of reactive metabolites, epichlorohydrin (ECH) and dichloroacetone (DCA). However, there is no direct evidence for the formation of these metabolites from exposure to DCP in rodents due to the challenges of measuring these reactive intermediates directly in vivo. The objective of this work was to investigate the metabolism of DCP to ECH and DCA in vivo by first developing a sensitive analytical method in a suitable biological matrix and analyzing samples from rats administered DCP. DCA reacted rapidly in vitro in rat blood, plasma, and liver homogenate, precluding its detection. Because ECH rapidly disappeared in liver homogenate, but was relatively long-lived in plasma and blood in vitro, blood was selected for analysis of this metabolite. Following a single oral dose of 50 mg\/kg DCP in male or female Harlan Sprague\u2013Dawley rats, ECH was detected in blood with a maximum concentration reached at \u226413.7 min. ECH was cleared rapidly with a half-life of ca. 33 and 48 min in males and females, respectively. Following a single oral dose of 25 mg\/kg ECH in male and female rats, the elimination half-life of ECH was ca. 34 and 20 min, respectively; the oral bioavailability of ECH was low (males, 5.2%; females, 2.1%), suggesting extensive first pass metabolism of ECH following oral administration. The area under the concentration vs time curve for ECH following oral administration of DCP and intravenous administration of ECH was used to estimate the percent of the DCP dose converted to ECH in rats. On the basis of this analysis, we concluded that in male and female rats following oral administration of 50 mg\/kg DCP, \u22651.26% or \u22651.78% of the administered dose was metabolized to ECH, respectively.<\/jats:p>","DOI":"10.1021\/tx500239q","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T18:50:35Z","timestamp":1411671035000},"page":"1787-1795","source":"Crossref","is-referenced-by-count":15,"title":["Formation of Epichlorohydrin,\na Known Rodent Carcinogen,\nFollowing Oral Administration of 1,3-Dichloro-2-propanol in Rats"],"prefix":"10.1021","volume":"27","author":[{"given":"Suramya","family":"Waidyanatha","sequence":"first","affiliation":[{"name":"National Institute of Environmental Health Sciences , , , ,","place":["Research Triangle Park, North Carolina, United States, 27709"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman F.","family":"Gaudette","sequence":"additional","affiliation":[{"name":"RTI International , , ,","place":["Research Triangle Park, North Carolina, United States, 27709"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Hong","sequence":"additional","affiliation":[{"name":"RTI International , , ,","place":["Research Triangle Park, North Carolina, United States, 27709"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Fennell","sequence":"additional","affiliation":[{"name":"RTI International , , ,","place":["Research Triangle Park, North Carolina, United States, 27709"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,9,25]]},"reference":[{"key":"2026092806065011800_cit1","unstructured":"(1992)  Toxicological\nprofile for 1,2,3-trichloropropane, pp 57\u201358, Agency for Toxic Substances and Disease\nRegistry, U.S. Public Health\nService, Atlanta, GA, http:\/\/www.atsdr.cdc.gov\/toxprofiles\/tp57-c4.pdf."},{"key":"2026092806065011800_cit2","unstructured":"(2005)  1,3-Dichloro-2-propanol [CAS No. 96-23-1]: review\nof toxicological\nliterature, National Toxicology Program, Research Triangle Park, NC, http:\/\/ntp.niehs.nih.gov\/ntp\/htdocs\/Chem_Background\/ExSumPdf\/dichloropropanol_508.pdf."},{"key":"2026092806065011800_cit3","unstructured":"(2001)  Evaluation of certain food additives\nand food contaminants.\nWHO technical report series 909, Joint FAO\/WHO\nExpert Committee on Food Additives, Geneva, Switzerland, http:\/\/www.who.int\/pcs\/jecfa\/trs909.pdf."},{"key":"2026092806065011800_cit4","unstructured":"(2003)  Position paper on chloropropanols, CX\/FAC 03\/34\n35th Session, CCFAC, Arusha, United Republic of Tanzania, ftp:\/\/ftp.fao.org\/codex\/ccfac35\/fa03_34e.pdf."},{"key":"2026092806065011800_cit5","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/BF01607726","article-title":"Levels of triaryl\nphosphates in human adipose tissue\nfrom Eastern Ontario","volume":"37","author":"LeBel","year":"1986","journal-title":"Bull. 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Toxicol."},{"key":"2026092806065011800_cit18","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/j.1600-0676.1993.tb00618.x","article-title":"Submassive\nhepatic necrosis induced by dichloropropanol","volume":"13","author":"Haratake","year":"1993","journal-title":"Liver"},{"key":"2026092806065011800_cit19","first-page":"375","article-title":"1,3-Dichloro-2-propanol","volume":"101","author":"IARC.","year":"2007","journal-title":"IARC\nMonogr."},{"key":"2026092806065011800_cit20","unstructured":"(2010)  Evidence\non the carcinogenicity of 1,3-dichloro-2-propanol\n(1,3-DCP; \u03b1,\u03b3-dichlorohydrin), Office of Environmental Health Hazard Assessment (OEHHA), California\nEnvironmental Protection Agency, Sacramento,\nCA, http:\/\/www.oehha.ca.gov\/prop65\/hazard_ident\/pdf_zip\/13dcp.pdf."},{"key":"2026092806065011800_cit21","first-page":"922","article-title":"Forestomach\ntumors induced by orally\nadministered epichlorohydrin in male Wistar rats","volume":"71","author":"Konishi","year":"1980","journal-title":"Gann"},{"key":"2026092806065011800_cit22","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0300-483X(85)90034-4","article-title":"Carcinogenicity\nstudy with epichlorohydrin (CEP) by gavage in rats","volume":"36","author":"Wester","year":"1985","journal-title":"Toxicology"},{"key":"2026092806065011800_cit23","first-page":"603","article-title":"Epichlorohydrin","volume":"71","author":"IARC.","year":"1997","journal-title":"IARC Monogr."},{"key":"2026092806065011800_cit24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0165-1218(94)90019-1","article-title":"Study of the genotoxic\nactivity of five chlorinated propanones using the SOS chromotest,\nthe Ames-fluctuation test and the newt micronucleus test","volume":"341","author":"Le Curieux","year":"1994","journal-title":"Mutat. Res."},{"key":"2026092806065011800_cit25","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/0041-008X(87)90192-X","article-title":"Chemical reactivity, cytotoxicity, and mutagenicity\nof chloropropanones","volume":"91","author":"Merrick","year":"1987","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"2026092806065011800_cit26","doi-asserted-by":"crossref","first-page":"595","DOI":"10.3109\/00498257909042326","article-title":"Epoxides as obligatory\nintermediates in the metabolism\nof \u03b1-halohydrins","volume":"9","author":"Jones","year":"1979","journal-title":"Xenobiotica"},{"key":"2026092806065011800_cit27","doi-asserted-by":"crossref","first-page":"13","DOI":"10.7888\/juoeh.14.13","article-title":"Identification\nand quantitative analysis of urinary metabolites of dichloropropanols\nin rats","volume":"14","author":"Koga","year":"1992","journal-title":"J. UOEH"},{"key":"2026092806065011800_cit28","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0278-6915(99)00012-5","article-title":"Depression\nof glutathione content, elevation of CYP2E1-dependent activation,\nand the principal determinant of the fasting-mediated enhancement\nof 1,3-dichloro-2-propanol hepatotoxicity in the rat","volume":"37","author":"Fry","year":"1999","journal-title":"Food Chem. Toxicol."},{"key":"2026092806065011800_cit29","first-page":"420","article-title":"Role of\nP450 in the metabolism-mediated glutathione depletion by 1,3-dichloro-2-propanol\nand structural analogues","volume":"16","author":"Garle","year":"1997","journal-title":"Hum. Exp. Toxicol."},{"key":"2026092806065011800_cit30","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1080\/004982599238524","article-title":"Haloalcohols deplete\nglutathione when incubated with fortified liver fractions","volume":"29","author":"Garle","year":"1999","journal-title":"Xenobiotica"},{"key":"2026092806065011800_cit31","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/0887-2333(96)00001-X","article-title":"Effects of culture duration, cytochrome P-450 inhibition\nand glutathione depletion on toxicity of diverse xenobiotics","volume":"10","author":"Hammond","year":"1996","journal-title":"Toxicol. In Vitro"},{"key":"2026092806065011800_cit32","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0300-483X(96)03604-9","article-title":"Involvement of cytochrome P4502E1 in the toxicity of\ndichloropropanol to rat hepatocyte cultures","volume":"118","author":"Hammond","year":"1997","journal-title":"Toxicology"},{"key":"2026092806065011800_cit33","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0009-2797(99)00118-0","article-title":"Effect\nof cyanamide on toxicity and glutathione depletion\nin rat hepatocyte cultures: Differences between two dichloropropanol\nisomers","volume":"122","author":"Hammond","year":"1999","journal-title":"Chem.\u2013Biol. Interact."},{"key":"2026092806065011800_cit34","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/1382-6689(95)00007-0","article-title":"Toxicity\nof dichloropropanols in\nrat hepatocyte cultures","volume":"1","author":"Hammond","year":"1996","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"2026092806065011800_cit35","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1006\/taap.1998.8610","article-title":"The nature\nof halogen substitution\ndetermines the mode of cytotoxicity of halopropanols","volume":"155","author":"Hammond","year":"1999","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"2026092806065011800_cit36","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0887-2333(02)00008-5","article-title":"Modulation of hepatocytes\nthiol content by medium composition: Implications for toxicity studies","volume":"16","author":"Hammond","year":"2002","journal-title":"Toxicol. In Vitro"},{"key":"2026092806065011800_cit37","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1177\/096032719701600505","article-title":"Low-dose\ndiethyldithiocarbamate attenuates the hepatotoxicity of 1,3-dichloro-2-propanol\nand selectively inhibits CYP2E1 activity in the rat","volume":"16","author":"Stott","year":"1997","journal-title":"Hum. Exp. Toxicol."},{"key":"2026092806065011800_cit38","unstructured":"(2002)  1,3-Dichloro-2-propanol, Hazardous Substances\nData Bank, Bethesda, MD."},{"key":"2026092806065011800_cit39","unstructured":"(2000)  1,3-Dichloro-2-propanol: toxicity, carcinogenicity,\ntumorigenicity,\nmutagenicity, and teratogenicity, RTECS, Hamilton, ON, Canada, no. UB1400000."},{"key":"2026092806065011800_cit40","volume-title":"Guide\nfor the Care and Use of Laboratory Animals","author":"National Research Council.","year":"1996"},{"key":"2026092806065011800_cit41","volume-title":"Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts\nand Applications","author":"Gabrielsonn","year":"2005"},{"key":"2026092806065011800_cit42","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1023\/A:1018943613122","article-title":"Physiological parameters\nin laboratory animals and\nhumans","volume":"10","author":"Davies","year":"1993","journal-title":"Pharm. Res."},{"key":"2026092806065011800_cit43","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/0165-1218(83)90144-1","article-title":"Genotoxicty,\nmetabolism and blood kinetics of epichlorohydrin in mice","volume":"118","author":"Rossi","year":"1983","journal-title":"Mutat. Res."},{"key":"2026092806065011800_cit44","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1016\/0006-2952(83)90125-9","article-title":"Microsomal epoxide hydrolase in different\nrat strains","volume":"32","author":"Oesch","year":"1983","journal-title":"Biochem. Pharmacol."},{"key":"2026092806065011800_cit45","first-page":"333","article-title":"Disposition and metabolism\nof [2\u201314C]epichlorohydrin after\noral administration to rats","volume":"13","author":"Gingell","year":"1985","journal-title":"Drug Metab. Dispos."},{"key":"2026092806065011800_cit46","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0009-2797(98)00099-4","article-title":"Adducts with\nhaemoglobin and with DNA in epichlorohydrin-exposed rats","volume":"117","author":"Landin","year":"1999","journal-title":"Chem.\u2013Biol. Interact."},{"key":"2026092806065011800_cit47","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.jchromb.2008.11.028","article-title":"Quantification of N-(3-chloro-2-hydroxypropyl)valine in human haemoglobin\nas a biomarker of epichlorohydrin exposure by gas chromatography-tandem\nmass spectrometry with stable-isotope dilution","volume":"877","author":"Bader","year":"2009","journal-title":"J. Chromatogr. B: Anal. Technol. Biomed. Life Sci."},{"key":"2026092806065011800_cit48","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/B978-008045382-8.00163-5","article-title":"Mechanistic and structural studies\nof microbial\ndehalogenases: how nature cleaves a carbon-halogen bond","volume-title":"Comprehensive Natural Products II: Chemistry and Biology","author":"Poelarends","year":"2010"},{"key":"2026092806065011800_cit49","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0014-5793(94)80278-5","article-title":"Sequence similarity\nof mammalian\nepoxide hydrolases to the bacterial haloalkane dehalogenase and other\nrelated proteins. Implication for the potential catalytic mechanism\nof enzymatic epoxide hydrolase","volume":"338","author":"Arand","year":"1994","journal-title":"FEBS Lett."},{"key":"2026092806065011800_cit50","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1093\/bioinformatics\/bth284","article-title":"The database of epoxide\nhydrolases and haloalkane dehalogenases: one structure, many functions","volume":"20","author":"Barth","year":"2004","journal-title":"Bioinformatics"}],"container-title":["Chemical Research in Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/tx500239q","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/crtoec\/article-pdf\/27\/10\/1787\/12921719\/tx500239q.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/crtoec\/article-pdf\/27\/10\/1787\/12921719\/tx500239q.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T10:30:34Z","timestamp":1790591434000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/crtoec\/article\/27\/10\/1787\/1303578\/Formation-of-Epichlorohydrin-a-Known-Rodent"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,25]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,9,25]]},"published-print":{"date-parts":[[2014,10,20]]}},"URL":"https:\/\/doi.org\/10.1021\/tx500239q","relation":{},"ISSN":["0893-228X","1520-5010"],"issn-type":[{"value":"0893-228X","type":"print"},{"value":"1520-5010","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,25]]}}}