Urinary metabolites from F344 rats and B6C3F1 mice coadministered acrylamide and acrylonitrile for 1 or 5 days

The purpose of this study was to examine the feasibility of using C-13 NMR spectroscopy to analyze urinary metabolites produced following-coadministration of two structurally similar carbon-13-labeled compounds to rodents. Acrylonitrile(AN) and acrylamide (AM) are used in the chemical industry to manufacture plastics and polymers. These compounds are known to produce carcinogenic, reproductive, or neurotoxic effects in laboratory animals. The potential for human exposure to AN and AM occurs in manufacturing facilities and environmentally, Male F344 rats and B6C3F1 mice were coadministered po [1,2,3-C-13]AN (16-17 mg/kg) and [1,2,3-C-13]AM (21-22 mg/kg) after 0 or 4 days of administration of unlabeled AN or AM. Urine was collected for 24 h following administration of the C-13-labeled compounds and analyzed by C-13 NMR spectroscopy. Rats and mice excreted metabolites derived from glutathione (GSH) conjugation with AM or AN or derived from GSH conjugation with the epoxides cyanoethylene oxide (CEO) or glycidamide (GA). GA and its hydrolysis product were also detected in the urine of rats and. mice. For mice; an increased urinary excretion of total AN- and total AM-derived metatsolites (p < 0.05) an repeated coadministration suggested a possible increase in metabolism via oxidation, In addition, mice had an increased (p < 0.05) precentage of dose excreted as metabolites derived from GSH conjugation with AM, AN, CEO, or GA after five exposures as compared with One exposure that may be related to a significant increase in the synthesis of GSH or an increase in glutathione transferase activity. The only significant, (p < 0.05) increase between one. and five exposures for tl-ie rat was in the percentage of metabolites produced following conversion of AM to GA. The use of C-13 NMR spectroscopy has provided a powerful methodology for elucidation of the metabolism of two C-13-labeled chemicals administered simultaneously.