Urinary Metabolites from F344 Rats and B6C3F1 Mice Coadministered Acrylamide and Acrylonitrile for 1 or 5 Days

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• 作者：Susan C. J. Sumner ; Leena Selvaraj ; Sara K. Nauhaus ; and Timothy R. Fennell
• 刊名：Chemical Research in Toxicology
• 出版年：1997
• 出版时间：October 1997
• 年：1997
• 卷：10
• 期：10
• 页码：1152 - 1160
• 全文大小：162K
• 年卷期：v.10,no.10(October 1997)
• ISSN：1520-5010

文摘

The purpose of this study was to examine the feasibility of using¹³C NMR spectroscopy toanalyze urinary metabolites produced following coadministration of twostructurally similarcarbon-13-labeled compounds to rodents. Acrylonitrile (AN) andacrylamide (AM) are used inthe chemical industry to manufacture plastics and polymers. Thesecompounds are known toproduce carcinogenic, reproductive, or neurotoxic effects in laboratoryanimals. The potentialfor human exposure to AN and AM occurs in manufacturing facilities andenvironmentally.Male F344 rats and B6C3F1 mice were coadministered po[1,2,3-¹³C]AN (16-17 mg/kg) and[1,2,3-¹³C]AM (21-22 mg/kg) after 0 or 4 days ofadministration of unlabeled AN or AM. Urinewas collected for 24 h following administration of the¹³C-labeled compounds and analyzed by¹³C NMR spectroscopy. Rats and mice excretedmetabolites derived from glutathione (GSH)conjugation with AM or AN or derived from GSH conjugation with theepoxides cyanoethyleneoxide (CEO) or glycidamide (GA). GA and its hydrolysis productwere also detected in theurine of rats and mice. For mice, an increased urinary excretionof total AN- and total AM-derived metabolites (p < 0.05) on repeated coadministrationsuggested a possible increase inmetabolism via oxidation. In addition, mice had an increased(p < 0.05) percentage of doseexcreted as metabolites derived from GSH conjugation with AM, AN, CEO,or GA after fiveexposures as compared with one exposure that may be related to asignificant increase in thesynthesis of GSH or an increase in glutathione transferase activity.The only significant (p <0.05) increase between one and five exposures for the rat was in thepercentage of metabolitesproduced following conversion of AM to GA. The use of¹³C NMR spectroscopy has provideda powerful methodology for elucidation of the metabolism of two¹³C-labeled chemicalsadministered simultaneously.