Formation of N-nitrosomorpholine in mice treated with morpholine and exposed to nitrogen dioxide.
The possibility of N-nitrosomorpholine formation was investigated in mice treated with morpholine and then exposed to 45 p.p.m. nitrogen dioxide in an inhalation chamber for 2 h. Following this treatment, the mice were frozen and pulverized in liquid nitrogen and concentrated extracts from the powders of these animals were analyzed for N-nitrosomorpholine using a thermal energy analyzer interfaced to a gas chromatograph. The data indicate that nitrogen dioxide exposure causes the nitrosation of morpholine in vivo. Additional data show that significant levels of artifactually formed N-nitrosomorpholine are found in control animals that are treated with morpholine after exposure to nitrogen dioxide for 2 h unless a combination of L-ascorbic acid and d,1-alpha-tocopherol are used to inhibit nitrosation during the homogenization, extraction, and analysis of the samples. The need for both a lipid phase nitrosation blocker (d,1-alpha-tocopherol) and an aqueous phase nitrosation blocker (L-ascorbic acid) indicates that the nitrosation of morpholine occurs in both a lipid and an aqueous phase in vitro and therefore may occur in both a lipid and an aqueous environment in vivo. The data from this study also demonstrate the importance of adding suitable inhibitors of nitrosation, such as L-ascorbic acid and d,1-alpha-tocopherol to the extraction solution to prevent possible artifactual formation of N-nitrosomorpholine during the extraction and analysis of the samples.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002273:Carcinogens / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D009025:Morpholines / Q000378:metabolism*; D009585:Nitrogen Dioxide / Q000378:metabolism* / Q000494:pharmacology; D009602:Nitrosamines / Q000302:isolation & purification / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology
D002273:Carcinogens; D009025:Morpholines; D009602:Nitrosamines; D014810:Vitamin E; C002741:N-nitrosomorpholine; C037574:morpholine; D001205:Ascorbic Acid; D009585:Nitrogen Dioxide