N-nitroso compounds and man: sources of exposure, endogenous formation and occurrence in body fluids

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Based on recent analytical data, total human exoenous exposure to N-nitrosamines is estimated to be 1.10 μmol/day: the major exposure sources are the diet (0.79 μmol/day, 80–120 μg/day; 72%), occupational exposure (0.15–0.30 μmol/day; 25%), cigarette smoking (0.02 μmol/day, 3.4 μg/day; 2%), and miscellaneous minor sources, including pharmaceutical products, cosmetics, indoor and outdoor air (0.001 μmol/day, 0.1 μg/day; 1%). Excretion of apparent total N-nitroso compounds (ATNC) in healthy adults is estimated to be 1.30 ± 1.05 μmol/day in urine and between 1.56 ± 1.56 and 3.17 ± 2.58 μmol/day in faeces. The excretion of volatile N-nitrososarcosine, (N-nitrosodimethylamine), and N-nitrosamino acids and their derivatives (N-nitrososarcosine, N-nitrosoproline, N-nitrosothiazolidine-4-carboxylic acid and N-nitroso-2-methylthiazolidine-4-carboxylic acid) accounts for approximately 0.03% and 16.0% of urinary ATNC, respectively. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol and its O-glucuronide conjugate, two metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone present in urine of smokers, account for 0.2% of the urinary ATNC response; > 1.5% of the excretion of currently identified N-nitroso compounds in urine. The remaining N-nitroso compounds excreted in urine and those present in faeces are still unidentified. A crude mass balance between exogenous exposure and excretion in urine and faeces indicates that 45–75% of the total human exposure to N-nitroso compounds results through in vivo formation.

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