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-co administration of two structurally similar carbon-13-labeled compounds to rodents. Acrylonitrile(AN) and acrylamide (AM) are used in the che mical industry to manufacture plastics and polymers. These compounds a re known to produce carcinogenic, reproductive, or neurotoxic effects in laboratory animals. The potential for human exposure to AN and AM o ccurs in manufacturing facilities and environmentally, Male F344 rats and B6C3F1 mice were coadministered po [1,2,3-C-13]AN (16-17 mg/kg) an d [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 administrat ion of the C-13-labeled compounds and analyzed by C-13 NMR spectroscop y. Rats and mice excreted metabolites derived from glutathione (GSH) c onjugation with AM or AN or derived from GSH conjugation with the epox ides cyanoethylene oxide (CEO) or glycidamide (GA). GA and its hydroly sis product were also detected in the urine of rats and. mice. For mic e; an increased urinary excretion of total AN- and total AM-derived me tatsolites (p < 0.05) an repeated coadministration suggested a possibl e increase in metabolism via oxidation, In addition, mice had an incre ased (p < 0.05) precentage of dose excreted as metabolites derived fro m GSH conjugation with AM, AN, CEO, or GA after five exposures as comp ared with One exposure that may be related to a significant increase i n the synthesis of GSH or an increase in glutathione transferase activ ity. The only significant, (p < 0.05) increase between one. and five e xposures for tl-ie rat was in the percentage of metabolites produced f ollowing conversion of AM to GA. The use of C-13 NMR spectroscopy has provided a powerful methodology for elucidation of the metabolism of t wo C-13-labeled chemicals administered simultaneously.