In vivo formation of N-nitrosomorpholine in CD-1 mice exposed by inhalation to nitrogen dioxide and by gavage to morpholine.

Male CD-1 mice were exposed to approximately 20 ppm nitrogen dioxide (NO2) for 5-6 hours, to 1 g morpholine/kg body weight by gavage, or to both. Treatments were repeated daily for 5 consecutive days. N-nitrosomorpholine (NMOR) was found in whole carcasses (16-146 ng NMOR/mouse) in all animals that had been exposed to both NO2 and to morpholine, but NMOR was not found in tissues from animals that had been exposed to either chemical alone. Approximately one-third of the NMOR was found in the gastrointestinal tract, mainly in the stomach. The coadministration of 2 g sodium ascorbate/kg body weight or 1 g alpha-tocopheryl acetate/kg body weight had no effect on the amount of NMOR that was found in any tissue. Another possible product of the interaction of NO2 and morpholine, N-nitromorpholine, was not detected in any tissue. We concluded that the repeated, concurrent exposures of mice to NO2 by inhalation and to morpholine by gavage resulted in the in vivo formation of significant quantities of NMOR. The biological significance of the observation remains unknown.