TY  - CHAP
A1  - Shephard, S. E.
A1  - Schlatter, C.
A1  - Lutz, Werner K.
T1  - Model risk analysis of nitrosatable compounds in the diet as precursors of potential endogenous carcinogens
N2  - The potential health risk posed by the endogenous formation of N-nitroso compounds (NOC) from nitrosation of dietary ureas, guanidines, amides, amino acids and amanes (primary, secondary and aromatic) was estimated according to the model:
Risk = ( daily intake of precursor] X (gastric concentration of nitrite ]n X [nitrosatability rate constant] X [cilrcinogenicity of derivative].
The daily intakes ofthese compound classes span five orders ofmagnitude (100 g/day amides, top; 1-10 mg/day secondary amines, ureas, bottom); the nitrosation rate constants span seven orders of magnitude (aryl amines, ureas, top; amides, secondary amines, bottom); and the carcinogenicity estimates span a 10 000-fold range from 'very strong' to 'virtually noncarcinogenic'. The resulting risk estimates likewise span an enormous range (nine orders of magnitude ): dietary ureas and aromatic amines combined with high nitrite concentration could pose as great a risk as the intake of preformed N-nitrosodimethylamine in the diet. In contrast, the risk posed by the in-vivo nitrosation of primary and secondary amines is probably negligible. The risk contributed by amides (including protein), guanidines and primary amino acids is intermediate between these two extremes.
KW  - Risikoanalyse
KW  - Carcinogen
KW  - Ernährung
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86188
ER  - 
TY  - JOUR
A1  - Shephard, S. E.
A1  - Lutz, Werner K.
T1  - Nitrosation of dietary precursors
N2  - The diet contains a large number of constituents which can be nitrosated in the gastrointestinal tract (especially in the stomach) to potentially carcinogenic nitroso compounds (NOC). The nitrosation of food mixtures has been investigated with a number of assays, such as chemical analysis or detection of alkylating potential, mutagenicity and carcinogenicity. Relatively good information is available on the formation of stable nitrosamines using high nitrite concentrations. Little is known, however, about the formation of chemically unstable NOC at low nitrite concentration and their genotoxicity in target cells. A comparison of the precursor classes, alkylamines, aromatic amines, amino acids, amides and peptides, ureas and guanidines, reveals a vast range, both with respect to daily intake (105-fold) and nitrosation rate (104-fold both for 1st and 2nd order nitrite dependence). A total span of 108 results for the relative yield of NOC in the stomach. The endogenous NOC burden from dietary ureas and aromatic amines may represent as large a hazard as the intake of preformed NOC. Recent evidence also indicates that heterocyclic amines and phenols must be considered and that the half-life of nitrosated a-amino acids can be much longer than that of nitrosated primary alkylamines. In these classes, more information should be collected on dietary concentrations, on the nitrosation under realistic conditions and on the genotoxicity in stomach lining cells. Within a chemical precursor class, a wide range is seen with respect to alkylating potency. It cannot, therefore, be excluded that individual precursors within the top ranking classes might become more important than single preformed NOC. Not considered in the above analysis but probably just as important for a risk evaluation in a population is the knowledge of the nitrosation conditions and target cell susceptibility in individuals.
KW  - Ernährung
KW  - diet
KW  - amine
KW  - amino acid
KW  - urea
KW  - nitrosation
KW  - nitroso compound
KW  - endogenous
KW  - stomach
KW  - alkylation
KW  - 4-(p-nitrobenzyl)pyridine
KW  - DNA binding
KW  - genotoxic
KW  - mutagen
KW  - carcinogen
KW  - Nitrosierung
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-70311
ER  - 
TY  - JOUR
A1  - Adami, Hans-Olov
A1  - Dragsted, Lars
A1  - Enig, Bent
A1  - Hansen, Jens
A1  - Haraldsdóttir, Jóhanna
A1  - Hill, Michael J.
A1  - Holm, Lars Erik
A1  - Knudsen, Ib
A1  - Larsen, Jens-Jorgen
A1  - Lutz, Werner K.
A1  - Osler, Merete
A1  - Overvad, Kim
A1  - Sabroe, Svend
A1  - Sanner, Tore
A1  - Strube, Michael
A1  - Sorensen, Thorkild I. A.
A1  - Thorling, Eivind B.
T1  - Report from the working group on diet and cancer.
N2  - No abstract available.
KW  - Krebs <Medizin>
KW  - Ernährung
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-71601
ER  -