While numerous laboratory studies have shown that carcinogenic nitrosamines can be formed from the aqueous nitrosation of environmentally prevalent tertiary amines there is accumulating evidence to suggest that the pathway from tertiary amine to nitrosamine is branched and less well understood than once thought. Our recent work shows that tertiary amines as well as secondary amines and N,N-dialkylamides produce nitrosamines when heated with ionic nitrite, ethylene glycol or glycerol, and an ester. This ester mediated nitrosation could explain the formation of carcinogenic nitrosamines in meats, toiletry articles, and metalworking fluids and the further elucidution of its scope and mechanism are proposed. In other experiments we have shown that a tertiary amine modeling the malt alkaloid gramine rapidly produces dimethylnitrosamine by a new substitution mechanism of nitrosation. The investigation of this nitrosation pathway will be further explored along with other routes for producing nitrosamines from tertiary amines by acidic nitrosation. A basic study of the first formed inermediate in tertiary amine nitrosation, the nitrosammonium ion is proposed in order to better understand the limits of tertiary amine nitrosation. A rich array of nitrosamine products arise from the nitrosation of heterocyclic tertiary amines and some of these substances are unusually reactive suggesting their possible activity as direct acting carcinogens. The elaboration of he chemistry of some of these compounds and heterocyclic tertiary amine nitrosation is proposed. The possibility that triethanolamine is a precursor of N-nitrosodiethanolamine during metal grinding will be examined with a model grinding machine and 14C-labeled substrate in order to establish safety limits for the use of triethanolamine in nitrite free and ontaining metalworking fluids. It is hoped that our understanding of these nitrosation pathways can point toward specific inhibitors and inhibition techniques.
| Loeppky, R N; Tomasik, W; Kerrick, B E (1987) Nitroso transfer from alpha-nitrosamino aldehydes: implications for carcinogenesis. Carcinogenesis 8:941-6 |
