Urinary excretion of N-nitrosamines in rats and humans

Various sources may contribute to the total human exposure to nitrosamines (foods, drugs, cosmetics, polluted air and endogenous formation of N-nitroso compounds). The average intake of nitrosamines can be calculated using analytical data. The more relevant method of biological monitoring can be used, however, to estimate individual exposure, in which case possible in vivo formation may also be detected. Since blood measurements can be carried out only under great difficulty and reflect only the momentary situation, the urinary excretion of nitrosamines was studied in animal experiments. The urinary excretion of nitrosodimethylamine (NDMA), nitrosomorpholine (NMOR) and nitrosodiethanolamine (NDELA) in SD-rats was measured within 24 h after epicutaneous, intratracheal, oral and intravenous application. The dose range covered was 5, 50 and 500 micrograms/animal for NDMA, 4, 44 and 440 micrograms/animal for NMOR and 0.03-300 mg/animal for NDELA. Under the influence of diethylether, a 7- to 20-fold increase of excretion was observed. Biological monitoring in humans at low doses (10-100 micrograms NDMA) is possible only if the excretion rate is increased by administration of ethanol. By reducing the activity of metabolizing enzymes with ethanol or other suitable compounds, possible in vivo formation of nitrosamines might also be more easily detectable. Excretion rates do not seem to be dose-dependent in the ranges investigated.