Kinetics of nitrosamine formation in mice following oral administration of trace-level precursors.

Groups of 3-5 Swiss CD1 mice were gavaged with aqueous solutions of sodium nitrite (250 micrograms), followed immediately by morpholine (5 micrograms) or dimethylamine (250 micrograms). At subsequent intervals, up to 30-60 min, mice were frozen, pulverized in liquid nitrogen and extracted with methylene chloride. Volatile nitrosamines were then quantitatively determined using a Thermal Energy Analyzer, interfaced to GC or HPLC. Biosynthesis of both N-nitrosodimethylamine (NDMA) and N-nitrosomorpholine (NMOR) showed a time-dependent increase for 3 and 9 min, respectively, followed by a steady decline. Levels of NDMA and NMOR were generally less than 0.1 ng/g in control mice gavaged with amine or nitrite alone. Zero-time recovery of NDMA and NMOR ranged from 50-70% and 70-90%, respectively. Biosynthesis of NDMA and NMOR was inhibited by prior administration of ascorbic acid, sodium ascorbate or ammonium sulfamate.