IARC致癌物分类1

WORLD HEALTH ORGANIZATION INTERNATIONAL AGENCY FOR RESEARCH ON CANCER IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 17 Some N-Nitroso Compounds N-Nitrosodi-n-butylamine N-Nitrosodiethanolamine N-Nitrosodiethylamine N-Nitrosodimethylamine N-Nitrosodi-n-propylamine N-Nitrosodi-N-ethylurea N-Nitrosofolic acid N-Nitrosomethylethylamine N-Nitroso-N-methylurea N-Nitrosomethylvinylamine N-Nitrosomorpholine N'-Nitrosonornicotine N-Nitrosopiperidine N-Nitrosoproline and N-Nitrosohydroxyproline N-Nitrosopyrrolidine N-Nitrososarcosine Streptozotocin Last updated: 27 March 1998 N-NITROSODI-n-BUTYLAMINE VOL.: 17 (1978) (p. 51) CAS No.: 924-16-3 Chem. Abstr. Name: N-Butyl-N-nitroso-l-butamine 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitrosodi-n-butylamine is carcinogenic in all animal species tested: mice, rats, Syrian golden, Chinese and European hamsters, rabbits and guinea-pigs, after its oral, subcutaneous, intraperitoneal or intravenous administration. It produces benign and malignant tumours in the urinary bladder, oesophagus, liver, respiratory tract, stomach and intestine, and also leukaemia; it is particularly effective as a bladder carcinogen. It is carcinogenic following its administration prenatally and in single doses. The two metabolites, N-nitroso-n-butyl-N-(4-hydroxybutyl)amine and N-nitroso-n-butyl-N- (3-carboxypropyl)amine are also carcinogenic, the first in mice, rats, hamsters and dogs and the second in rats. When given orally to mice, N-nitroso-n-butyl-N-(4-hydroxybutyl)amine produces carcinomas of the urinary bladder; when given orally or intravesicularly to rats, it produces papillomas and carcinomas of the urinary bladder; when given subcutaneously to hamsters, it produces tumours of the urinary bladder and respiratory tract and cholangiocellular tumours; and when given subcutaneously to dogs, it produces urinary bladder tumours. N-nitroso-n-butyl-N-(3-carboxy- propyl)amine produces tumours of the urinary bladder in rats after its oral administration or intravesicular instillation. 5.2 Human data No case reports or epidemiological studies were available to the Working Croup. Available information on occurrence suggests that the general population may be exposed sporadically to low levels of N-nitrosodi-n- butylamine; however, no exposed group suitable for an epidemiological investigation has yet been identified. 5.3 Evaluation There is sufficient evidence of a carcinogenic effect of N-nitrosodi- n-butylamine in several experimental animal species. Although no epidemiological data were available, N-nitrosodi-n-butylamine should be regarded for practical purposes as if it were carcinogenic to humans. Previous evaluation: Vol. 4 (1974) Subsequent evaluation: Suppl. 7 (1987) (p. 67: Group 2B) For definition of terms, see Preamble Evaluation. Synonyms l DBNA l DBN l N,N-Di-n-butylnitrosamine l Di-n-butylnitrosamine l NDBA Last updated: 25 March 1998 N-NITROSODIETHANOLAMINE VOL.: 17 (1978) (p. 77) CAS No.: 1116-54-7 Chem. Abstr. Name: 2,2'-(Nitrosoimino)bis-ethanol 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitrosodiethanolamine is carcinogenic in rats after its oral administration and in hamsters after its subcutaneous injection. It produces hepatocellular carcinomas and renal adenomas in rats, and adenocarcinomas of the nasal cavity, papillary tumours of the trachea, hepatocellular adenomas and local fibrosarcomas in hamsters. 5.2 Human data No case reports or epidemiological studies were available to the Working Group. N-Nitrosodiethanolamine has been found in variable concentrations in tobacco, one pesticide formation, some cosmetic preparations and, in much higher concentrations (0.02-3%), in cutting fluids. These reports should permit the identification of exposed groups. 5.3 Evaluation There is sufficient evidence of a carcinogenic effect of N-nitrosodiethanolamine in two experimental animal species. In view of the widespread exposure to appreciable concentrations of N-nitrosodiethanolamine, efforts should be made to obtain epidemiological information. Although no epidemiological data were available, N- nitrosodiethanolamine should be regarded for practical purposes as if it were carcinogenic to humans. Subsequent evaluation: Suppl. 7 (1987) (p. 67: Group 2B); Vol. 77 (2000) For definition of terms, see Preamble Evaluation. Synonyms l Diethanolnitrosamine l NDELA l N-Nitroso-bis(2-hydroxyethyl)amine l Nitrosoimino diethanol Last updated: 25 March 1998 N-NITROSODIETHYLAMINE VOL.: 17 (1978) (p. 83) CAS No.: 55-18-5 Chem. Abstr. Name: N-Ethyl-N-nitroso-ethanamine 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitrosodiethylamine is carcinogenic in all animal species tested: mice, rats, Syrian golden, Chinese and European hamsters, guinea-pigs, rabbits, dogs, gerbils, pigs, monkeys, hedgehogs, various fish, frogs and birds. It induces benign and malignant tumours after its administration by various routes including ingestion, parenteral injection, inhalation and rectal instillation. The major target organs are the liver, respiratory and upper digestive tracts and kidney. It is carcinogenic following its administration prenatally and in single doses. In several studies, dose-response relationships were established. N-Nitroso-N-ethyl-N-(2-hydroxyethyl)amine, a metabolite of N-nitrosodiethylamine, produced mainly liver tumours after its oral administration to rats. 5.2 Human data No case reports or epidemiological studies were available to the Working Group. Available information on occurrence suggests that the general population may be exposed to low levels of N-nitrosodiethylamine; however, no exposed group suitable for an epidemiological investigation has yet been identified. 5.3 Evaluation There is sufficient evidence of a carcinogenic effect of N-nitrosodiethylamine in many experimental animal species. Although no epidemiological data were available, N-nitrosodiethylamine should be regarded for practical purposes as if it were carcinogenic to humans. Previous evaluation: Vol 1 (1972) Subsequent evaluation: Suppl. 7 (p. 67: Group 2A) For definition of terms, see Preamble Evaluation. Synonyms l DEN l DENA l N,N-Diethylnitrosamine l Diethylnitrosamine l Nitrosodiethylamine l NDEA Last updated: 27 March 1998 N-NITROSODIMETHYLAMINE VOL.: 17 (1978) (p. 125) CAS No.: 62-75-9 Chem. Abstr. Name: N-Methyl-N-nitrosomethanamine 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitrosodimethylamine is carcinogenic in all animal species tested: mice, rats, Syrian golden, Chinese and European hamsters, guinea-pigs, rabbits, ducks, mastomys, various fish, newts and frogs. It induces benign and malignant tumours following its administration by various routes, including ingestion and inhalation, in various organs in various species. It produces tumours, mainly of the liver, kidney and respiratory tract. It is carcinogenic following its administration prenatally and in single doses. In several studies, dose-response relationships were established. 5.2 Human data No case reports or epidemiological studies were available to the Working Group. Available information on occurrence suggests that the general population may be exposed to low levels of N-nitrosodimethylamine; however, no exposed group suitable for an epidemiological investigation has yet been identified. Reports of relatively high levels in certain pesticide formulations and of occupational exposures that may have occurred in the manufacture and use of rocket fuels may permit the identification of exposed groups. 5.3 Evaluation There is sufficient evidence of a carcinogenic effect of N-nitrosodimethylamine in many experimental animal species. Similarities in its metabolism by human and rodent tissues have been demonstrated. Although no epidemiological data were available (and efforts should be directed toward this end), N-nitrosodimethylamine should be regarded for practical purposes as if it were carcinogenic to humans. Previous evaluation: Vol 1 (1972) Subsequent evaluation: Suppl. 7 (1987) (p. 67: Group 2A) For definition of terms, see Preamble Evaluation. Synonyms l N,N-Dimethylnitrosamine l Dimethylnitrosamine l DMN l DMNA l NDMA Last updated: 27 March 1998 N-NITROSODI-n-PROPYLAMINE VOL.: 17 (1978) (p. 177) CAS No.: 621-64-7 Chem. Abstr. Name: N-nitroso-N-propyl-1-propanamine 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitrosodi-n-propylamine is carcinogenic in rats after its oral administration and in rats and hamsters after its subcutaneous injection. It produces benign and malignant tumours of the liver, kidney, oesophagus and respiratory tract. The metabolite N-nitroso-N-(2-hydroxy-n-propyl)-n-propylamine is also carcinogenic in rats and hamsters: it produces benign and malignant tumours of the respiratory tract and liver after its subcutaneous injection. 5.2 Human data No case reports or epidemiological studies were available to the Working Group. Available information on occurrence suggests that the general population may be exposed sporadically to low levels of N-nitrosodi-n- propylamine; however, no exposed group suitable for an epidemiological investigation has yet been identified. The report of relatively high levels in one pesticide formulation may permit the identification of exposed groups. 5.3 Evaluation There is sufficient evidence of a carcinogenic effect of N-nitrosodi-n-propylamine in two experimental animal species. Although no epidemiological data were available (and efforts should be directed toward this end), N- nitrosodi-n-propylamine should be regarded for practical purposes as if it were carcinogenic to humans. Subsequent evaluation: Suppl. 7 (1987) (p. 68: Group 2B) For definition of terms, see Preamble Evaluation. Synonyms l N,N-Di-n-propylnitrosamine l Di-n-propylnitrosamine l DPNA l NDPA l N-Nitrosodipropylamine Last updated: 27 March 1998 N-NITROSO-N-ETHYLUREA VOL.: 17 (1978) (p. 191) CAS No.: 759-73-9 Chem. Abstr. Name: N-Ethyl-N-nitrosourea 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitroso-N-ethylurea is carcinogenic in all animal species tested: mice, rats, Syrian golden hamsters, rabbits, opossums, pigs and monkeys. It produces benign and malignant tumours following its administration by different routes including single oral doses; the main target organ appears to vary with the route of administration. Prenatal exposure to the substance has been shown to be particularly effective in producing tumours of the nervous system. In several studies, dose-response relationships were established. 5.2 Human data No case reports or epidemiological studies were available to the Working Group. No information on the occurrence or use of N-nitroso-N-ethylurea was available. 5.3 Evaluation There is sufficient evidence of a carcinogenic effect of N-nitroso-N-ethylurea in several experimental animal species. Although no epidemiological data or information on occurrence were available, N-nitroso-N-ethylurea should be regarded for practical purposes as if it were carcinogenic to humans. Previous evaluation: Vol 1 (1972) Subsequent evaluation: Suppl. 7 (1987) (p. 63: Group 2A) For definition of terms, see Preamble Evaluation. Synonyms l ANH l ENU l 1-Ethyl-1-nitrosourea l NCS 45403 l NEU l Nitrosoethylurea Last updated: 27 March 1998 N-NITROSOFOLIC ACID VOL.: 17 (1978) (p. 217) CAS No.: 29291-35-8 Chem. Abstr. Name: N-{4-[(2-Amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino}- benzoyl-N-nitroso-L-glutanmic acid 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitrosofolic acid has been tested only in newborn mice by intraperitoneal injection, with inconclusive results. 5.2 Human data No case reports or epidemiological studies were available to the Working Group. No data on the occurrence or use of this material were available which would permit the identification of exposed groups. 5.3 Evaluation No evaluation of the carcinogenicity of N-nitrosofolic acid could be made on the basis of the available data. Subsequent evaluation: Suppl. 7 (1987) (p. 68: Group 3) For definition of terms, see Preamble Evaluation. Synonym l N-Nitroso-N-pteroyl-L-glutamic acid Last updated: 27 March 1998 N-NITROSOMETHYLETHYLAMINE VOL.: 17 (1978) (p. 221) CAS No.: 10595-95-6 Chem. Abstr. Name: N-Methyl-N-nitroso-ethamine 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitrosomethylethylamine is carcinogenic in rats after its oral administration, the only species and route tested: it produces hepatocellular carcinomas. 5.2 Human data No case reports or epidemiological studies were available to the Working Group. Available information on occurrence suggests that the general population may be exposed sporadically to low levels of N- nitrosomethylethylamine; however, no exposed group suitable for an epidemiological investigation has yet been identified. Reports suggest that tobacco smokers way be exposed to N-nitrosomthylethylamine together with other N-nitroso compounds. 5.3 Evaluation There is sufficient evidence of a carcinogenic effect of N-nitrosomethylethylamine in one experimental animal species. No epidemiological data were available. Subsequent evaluation: Suppl. 7 (1987) (p. 68: Group 2B) For definition of terms, see Preamble Evaluation. Synonyms l N,N-Methylethylnitrosamine l NEMA l NMEA Last updated: 27 March 1998 N-NITROSO-N-METHYLUREA VOL.: 17 (1978) (p. 227) CAS No.: 684-93-5 Chem. Abstr. Name: N-Methyl-N-nitrosourea 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitroso-N-methylurea is carcinogenic in all animal species tested: mice, rats, Syrian golden, Chinese and European hamsters, guinea-pigs, rabbits, gerbils, pigs, dogs and monkeys. It induces benign and malignant tumours following its administration by different routes, including ingestion. It produces tumours at different sites, including the nervous tissue, stomach, oesophagus, pancreas, respiratory tract, intestine, lymphoreticular tissues, skin and kidney. It is carcinogenic following its administration prenatally and in single doses. 5.2 Human data No case reports or epidemiological studies were available to the Working Group. Except for reported investigation of its use as a chemotherapeutic agent, no information on the occurrence or use of N-nitroso-N- methylurea was available. 5.3 Evaluation There is sufficient evidence of a carcinogenic effect of N-nitroso-N-methylurea in several experimental animal species. Although no epidemiological data were available, N-nitroso-N-methylurea should be regarded for practical purposes as if it were carcinogenic to humans. Previous evaluation: Vol 1 (1972) Subsequent evaluation: Suppl. 7 (1987) (p. 66: Group 2A) For definition of terms, see Preamble Evaluation. Synonyms l Methyl nitrosourea l 1-Methyl-1-nitrosourea l MNU l N-Nitroso-N-methylcarbamide l Nitrosomethylurea l NMH l NMU l NSC 23909 Last updated: 27 March 1998 N-NITROSOMETHYLVINYLAMINE VOL.: 17 (1978) (p. 257) CAS No.: 4549-40-0 Chem. Abstr. Name: Name: N-Methyl-N-nitroso-ethenylamine 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitrosomethylvinylamine is carcinogenic in rats, the only species tested. It produces carcinomas of the oesophagus, tongue and pharynx after its continuous oral administration and carcinomas of the nasal cavities after inhalation exposure. 5.2 Human data No case reports or epidemiological studies were available to the Working Group. Insufficient information on the occurrence or use of this compound was available to permit identification of exposed groups. 5.3 Evaluation There is sufficient evidence of a carcinogenic effect of N-nitrosomethylvinylamine in one experimental animal species. Although no epidemiological data were available, N-nitrosomethylvinylamine should be regarded for practical purposes as if it were carcinogenic to humans. Subsequent evaluation: Suppl. 7 (1987) (p. 68: Group 2B) For definition of terms, see Preamble Evaluation. Synonyms l N-Methyl-N-nitrosovinylamine l Methylvinylnitrosamine l NMVA Last updated: 27 March 1998 N-NITROSOMORPHOLINE VOL.: 17 (1978) (p. 263) CAS No.: 59-89-2 Chem. Abstr. Name: 4-Nitrosomorpholine 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitrosomorpholine is carcinogenic in mice, rats, Syrian golden, Chinese and European hamsters and various fish. Following its oral administration, it produces benign and malignant tumours of the liver and lung in mice, of the liver, kidney and blood vessels in rats and of the liver in hamsters. After its subcutaneous injection it produces tumours of the upper digestive and respiratory tracts in hamsters; it is carcinogenic after its administration in single doses. It produces liver tumours in rats following its intravenous injection. It produces liver tumours in various fish following its administration in tank-water. A study in hamsters has been reported in which a dose-response relationship was established. 5.2 Human data No case reports or epidemiological studies were available to the Working Group. Insufficient information on the occurrence of N-nitrosomorpholine was available to permit identification of exposed groups. 5.3 Evaluation There is sufficient evidence for a carcinogenic effect of N-nitrosomorpholine in several experimental animal species. Although no epidemiological data were available, N-nitrosomorpholine should be regarded for practical purposes as if it were carcinogenic to humans. Subsequent evaluation: Suppl. 7 (1987) (p. 68: Group 2B) For definition of terms, see Preamble Evaluation. Synonym l NMOR Last updated: 27 March 1998 N'-NITROSONORNICOTINE VOL.: 17 (1978) (p. 281) 5. Summary of Data Reported and Evaluation 5.1 Experimental data N'-Nitrosonornicotine is carcinogenic in rats, mice and Syrian golden hamsters. Following its oral administration to rats, it produces carcinomas of the upper digestive tract, mainly the oesophagus, and of the nasal cavities. In hamsters, its subcutaneous injection produces mainly tracheal tumours. In mice, its intraperitoneal injection produces lung tumours. 5.2 Human data No case reports or epidemiological studies were available to the Working Group. Available information on occurrence suggests that tobacco users are exposed to N'-nitrosonornicotine together with other N-nitroso compounds. 5.3 Evaluation There is sufficient evidence of a carcinogenic effect of N'-nitrosonornicotine in several experimental animal species. Although no epidemiological data were available, N'-nitrosonornicotine should be regarded for practical purposes as if it were carcinogenic to humans. Subsequent evaluations: Vol. 37 (1985); Suppl. 7 (1987) (p. 68: Group 2B) For definition of terms, see Preamble Evaluation. Last updated: 27 March 1998 N-NITROSOPIPERIDINE VOL.: 17 (1978) (p. 287) CAS No.: 100-75-4 Chem. Abstr. Name: 1-Nitroso-piperidine 5. Summary of Data Reported and Evaluation 5.1 Experimental data N-Nitrosopiperidine is carcinogenic in mice, rats, Syrian golden, European and Chinese hamsters and monkeys after its administration by oral and other routes. It produces benign and malignant tumours of the liver, lung, forestomach and oesophagus in mice, of the liver, oesophagus and respiratory system in rats, and of the upper digestive tract, respiratory system and li