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Endogenous formation of N-nitrosomorpholine in mice from 15NO2 by inhalation and morpholine by gavage
E W Van Stee1, R A Sloane, J E Simmons
1National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Abstract:
Male CD-1 mice were exposed to an nominal concentration of 20 p.p.m. of 15N-nitrogen dioxide (15NO2) for 6 h/day for 4 days and for 2 h on the day 5, and to 1 g morpholine/kg body wt by gavage daily for five consecutive days. N-Nitrosomorpholine (NMOR) was found in whole mice, stomachs, skins with hair, and remains. The sum of individual tissue concentrations measured separately was 3421 ng/tissue, where the average skin weighed 4.3 g, the average stomach weighed 1.0 g and the average remains weighed 22.2 g. The average whole mouse weighed 27.7 g and contained a total of 3903 ng of NMOR. The concentration of NMOR was highest in the skin, next highest in the stomach, and lowest in the remains. However, the total quantity of NMOR per tissue, while highest in the skin (83%), was next highest in the remains (14.8%) and lowest in the stomach (2.2%). GC-MS analysis served to distinguish between the NMOR of 15NO2 origin and that of other origin. All of the NMOR in the whole mouse homogenates was identified as 15NMOR. In the stomach 73% was identified as 14NMOR, representing 1.6% of the total NMOR in the mouse, and 27% as 15NMOR, representing 0.6% of the total NMOR in the mouse. N-Nitrosamine formation in vivo is discussed as a possibly ongoing mammalian process.
Insights
Mice exposed to nitrogen dioxide and morpholine produced N-nitrosomorpholine (NMOR). The study found NMOR in various tissues, with most originating from the nitrogen dioxide exposure, suggesting in vivo nitrosamine formation.
Area of Science:
- Toxicology
- Biochemistry
- Environmental Health
Background:
- Nitrogen dioxide (NO2) is an environmental pollutant.
- Morpholine is a chemical compound.
- N-nitrosamines are a class of potentially carcinogenic compounds.
Purpose of the Study:
- To investigate the in vivo formation of N-nitrosomorpholine (NMOR) in mice exposed to nitrogen dioxide (15NO2) and morpholine.
- To determine the distribution and origin of NMOR in different mouse tissues.
Main Methods:
- Male CD-1 mice were administered 15NO2 and morpholine daily for five days.
- NMOR levels and distribution were measured in whole mice, stomachs, skins, and remains using GC-MS analysis.
- Isotopic labeling (15N) was used to trace the origin of NMOR.
Main Results:
- NMOR was detected in all examined tissues, with the highest concentration in the skin.
- The majority of NMOR found in whole mouse homogenates was identified as 15NMOR, indicating formation from the administered 15NO2.
- A significant portion of NMOR in the stomach was identified as 14NMOR, suggesting endogenous or other exogenous sources.
Conclusions:
- The study provides evidence for in vivo N-nitrosamine formation in mammals, specifically NMOR from exposure to NO2 and morpholine.
- Nitrogen dioxide can contribute to endogenous N-nitrosamine synthesis.
- These findings highlight potential health risks associated with environmental exposure to nitrogen dioxide and amines.