National Toxicology Program

National Toxicology Program

CAS Registry Number: 62-75-9 Toxicity Effects

http://ntp.niehs.nih.gov/go/23659

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • N-Nitrosodimethylamine
  • N-METHYL-N-NITROSOMETHANAMINE (9CI)
  • TGMX RAT LIVER EVALUATION (N-NITROSODIMETHYLAMINE)
  • N-NITROSO-DIMETHYLAMINE
  • N-Nitrosodimethylamine (TGMX rat liver evaluation)

Human Toxicity Excerpts

  • IN 4 MEN, LAB EXPOSURE TO ... /NDMA/ GAVE RISE TO ACUTE LIVER NECROSIS WHICH LATER DEVELOPED INTO CIRRHOSIS; IN 1 CASE, THE ACUTE LIVER INJURY PROVED TO BE FATAL.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V17 151 (1978)] **PEER REVIEWED**
  • ... TWO CASES OF POISONING FROM DIMETHYLNITROSAMINE ... IN SURVEY OF LARGE AUTOMOBILE FACTORY. APPARENTLY, THE ACTION OF THE POISON WAS ON THE LIVER, PRODUCING CIRRHOSIS WITH JAUNDICE & ASCITES.[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974., p. 311] **PEER REVIEWED**
  • IN 8 HR PERIOD, FIVE MEMBERS OF TWO KINDRED FAMILIES SUDDENLY BECAME ILL WITH NAUSEA, VOMITING & MALAISE. THIS WAS FOLLOWED BY ACUTE LIVER DISEASE, GENERALIZED BLEEDING, & LOW PLATELET COUNT. 2 OF THE PATIENTS DIED FOUR AND FIVE DAYS AFTER ONSET. DMNA HAD BEEN ADDED TO BEVERAGES.[COOPER SW, KIMBROUGH RD; J FORENSIC SCI 25 (4): 874-82 (1980)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7430995?dopt=Abstract" target=new>PubMed Abstract</a>
  • UNSCHEDULED DNA SYNTH ... OBSERVED ... IN HUMAN FIBROBLASTS IN CULTURE IN PRESENCE OF NDMA & MOUSE LIVER MICROSOMAL FRACTION.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V17 150 (1978)] **PEER REVIEWED**
  • Systemic effects are characterized by onset in a few hr of nausea and vomiting, abdominal cramps and diarrhea. ... Headache, fever, weakness ... may occur.[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 669] **PEER REVIEWED**
  • DIMETHYLNITROSAMINE (NDMA) WAS DETECTED AT LEVELS OF ABOUT 32 UG/L IN DIALYZATE FROM 5 OF 16 DIALYSIS UNITS SURVEYED /SRP: NDMA ENTERED DIALYSIS UNITS VIA PLASTIC COMPONENTS OF THE DIALYZER/. BLOOD DRAWN FROM PATIENTS AT 1 OF THESE UNITS IN WHICH NDMA WAS RAISED IN THE DIALYZATE SHOWED A SIGNIFICANT INCREASE IN THE AMOUNT OF NDMA IN THE PATIENT'S BLOOD WHEN PREDIALYSIS LEVELS WERE COMPARED WITH 15 MIN INTRADIALYSIS LEVELS.[SIMENHOFF ML ET AL; J AM MED ASSOC 250 (15): 2020-4 (1983)] **PEER REVIEWED**
  • ... Although it is acknowledged that endogenous formation of N-nitroso compounds has been associated with increased risk of certain cancers, eg, stomach and esophagus, it was concluded that "no convincing epidemiological evidence has been presented concerning the etiological role of these compounds in human cancer." Likewise, in spite of several epidemiological studies "consistent with the hypothesis that exposure of humans to high levels of nitrate and/or nitrite may be associated with an increased incidence of cancers of the stomach and esophagus," the overall "epidemiological evidence suggesting that nitrate, nitrite, and N-nitroso compounds play a role in the development of cancer in humans is largely circumstantial." /N-Nitroso Cmpd/[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 513] **PEER REVIEWED**
  • In persons with acute poisoning due to systemic exposure, headaches, a feeling of generalized malaise, fever, and weakness often occur. Gastrointestinal effects are frequent and include abdominal cramping and nausea. Vomiting and diarrhea occur within hours of absorption. Liver enlargement and jaundice may follow.[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 1277] **PEER REVIEWED**
  • ... Health hazards ... related to the consumption of water containing large concentrations of nitrate (or nitrite) ... /include/ potential formation of carcinogenic nitrosamines. /Nitrosamines/[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 416] **PEER REVIEWED**
  • Caution: Potential symptoms of overexposure are nausea, vomiting, diarrhea and abdominal cramps; headache; fever; enlarged liver, jaundice; reduced function of liver, kidneys and lungs.[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1140] **PEER REVIEWED**
  • Has caused fatal liver disease in humans. Symptoms include headache, fever, weakness, nausea, vomiting, dizziness, diarrhea, GI hemorrhage, hepatomegaly, jaundice, and ascites.[Prager, J.C. Environmental Contaminant Reference Databook Volume 1. New York, NY: Van Nostrand Reinhold, 1995., p. 611] **PEER REVIEWED**
  • DNA, ISOLATED FROM 2 SAMPLES OF HUMAN LIVER OBTAINED FROM SUSPECTED DIMETHYLNITROSAMINE POISONING, CONTAINED 1363-1373 UMOL OF 7-METHYLGUANINE/MOLE OF GUANINE & 273-317 UMOLE OF O6-METHYLGUANINE/MOLE OF GUANINE. FROM DNA METHYLATION LEVELS, IT IS EST THAT VICTIM OF DIMETHYLNITROSAMINE-POISONING WAS EXPOSED TO DOSE OF 20 MG OR MORE/KG OF BODY WT.[HERRON DC, SHANK RC; CANCER RES 40 (9): 3116-17 (1980)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7427930?dopt=Abstract" target=new>PubMed Abstract</a>

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Non-Human Toxicity Excerpts

  • ADMIN BY STOMACH TUBE OF 1.6, 1.0 & 1.0 MG/ANIMAL OVER 5 WK, OR OF 1 DOSE OF 1.6 MG/ANIMAL, TO SYRIAN GOLDEN HAMSTERS INDUCED CHOLANGIOADENOMA, CHOLANGIOCARCINOMAS & HEMANGIOSARCOMAS AS WELL AS HEMANGIOENDOTHELIOMAS OF LIVER.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V17 137 (1978)] **PEER REVIEWED**
  • WEEKLY SC INJECTIONS OF 0.5-1.0 MG NDMA FOR 6-20 WK ... CAUSED ... ESTHESIONEUROEPITHELIOMAS OF NASAL CAVITY IN SYRIAN GOLDEN HAMSTERS.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V17 139 (1978)] **PEER REVIEWED**
  • MALE GUINEA PIGS GIVEN 1-2 MG/KG BODY WT ORALLY FOR 40-55 WK DEVELOPED PAPILLARY CHOLANGIOMAS & LIVER-CELL CARCINOMAS. ... DOSES OF 25 PPM & 50 PPM GIVEN TO RABBITS IN DIET FOR 17-51 WK RESULTED IN HEPATOCELLULAR CARCINOMA WITH LUNG METASTASES & BENIGN PAPILLARY CHOLANGIOMAS. DOSES OF 300 PPM, 1200 PPM, 4800 PPM & 19200 PPM GIVEN IN DIET FOR MORE THAN 6 MO INDUCED ADENOMAS & ADENOCARCINOMAS OF LIVER /IN RAINBOW TROUT/.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V1 99 (1972)] **PEER REVIEWED**
  • MASTOMYS (RATS): TWICE-WEEKLY SC INJECTIONS OF 0.1 MG NDMA PER ANIMAL FOR 10 TO 44 WEEKS INDUCED LIVER TUMORS IN 6/36 MALES: 2 CHOLANGIOMAS, 2 CHOLANGIOCARCINOMAS, 1 HEMANGIOENDOTHELIOMA AND 1 HEPATIC CELL CARCINOMA; NONE WERE SEEN IN FEMALES. IN CONTROLS, 4/82 LIVER TUMORS WERE SEEN IN FEMALES AND NONE IN MALES.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V17 140 (1978)] **PEER REVIEWED**
  • RAT: SINGLE OR REPEATED INHALATION EXPOSURES ... RESULTED IN TUMORS OF NASAL CAVITIES & KIDNEYS. ... RATS GIVEN A SINGLE INJECTION OF 18 MG/KG BODY WT EITHER IM, RETROPERITONEALLY OR DIRECTLY INTO THE KIDNEY, DEVELOPED RENAL TUMORS.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V1 100 (1972)] **PEER REVIEWED**
  • ... VAPOR CAUSED LIVER DAMAGE, ASCITES, & DISRUPTION OF BLOOD COAGULATION WITH BLEEDING IN DOGS, RATS, & MICE. CONCENTRATION: DOG, 16-144 PPM/4 HR INHALATION; RATS, 51-151 PPM/4 HR INHALATION; MICE, 39-60 PPM/4 HR INHALATION.[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 2788] **PEER REVIEWED**
  • IN MICE, SINGLE OR REPEATED INJECTIONS OF 12.5-75 MG/KG BODY WT NDMA DURING LAST DAYS OF PREGNANCY RESULTED IN LUNG ADENOMAS & HEPATOMAS IN OFFSPRING. NDMA INDUCED A LOW FREQUENCY OF KIDNEY TUMORS IN OFFSPRING OF PREGNANT RATS TREATED DURING LAST WEEK OR DURING THE WHOLE PREGNANCY (TOTAL DOSE, 11 MG) .[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V17 142 (1978)] **PEER REVIEWED**
  • DIMETHYLNITROSAMINE REQUIRES MAMMALIAN METABOLIC ACTIVATION BEFORE SHOWING MUTAGENIC ACTIVITY. USING A COMPLEMENT-RESISTANT ESCHERICHIA COLI STRAIN INJECTED INTO MICE GIVEN A SINGLE DOSE OF DMN, A LINEAR RESPONSE CURVE WAS ESTABLISHED USING AMPICILLIN & NALIDIXIC ACID AS 2 FORWARD MUTATION MARKERS.[NEALE S, SOLT AK; CHEM-BIOL INTERACT 31 (2): 221-26 (1980)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6993028?dopt=Abstract" target=new>PubMed Abstract</a>
  • AN IN VIVO INTRASANGUINE HOST-MEDIATED ASSAY REVEALED THAT MUTATIONS OCCURRED @ SIGNIFICANT RATE IN SALMONELLA TYPHIMURIUM G-46 EMPLOYED AS INDICATOR ORGANISMS RECOVERED FROM LIVER, LUNG, KIDNEY AND SPLEEN OF NDMA-TREATED MICE, COMPARED TO NEGATIVE CONTROL ANIMALS.[BAKSHI K, BRUSICK D; MUTAT RES 72 (1): 79-89 (1980)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7003367?dopt=Abstract" target=new>PubMed Abstract</a>
  • SHORT-TERM MAMMALIAN CARCINOGENICITY TEST IS PRESENTED IN WHICH AN IN VIVO ADMIN TO RATS IS FOLLOWED AFTER 2 WK BY IN VITRO CULTURE OF PERITONEAL CELLS. THE INCIDENCE OF RATS SHOWING TRANSFORMED COLONIES IN CULTURES AFTER SINGLE NDMA DOSE OF 20 MG/KG WAS NEARLY DOUBLE THAT REPORTED FOR RATS DEVELOPING TUMORS AFTER A HIGHER SINGLE DOSE OF 30 MG/KG.[NASHED N, CHANDRA P; CANCER LETT 10 (2): 95-108 (1980)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/7459837?dopt=Abstract" target=new>PubMed Abstract</a>
  • DIMETHYLNITROSAMINE WAS ACTIVATED TO MUTAGEN ON INCUBATION WITH DROSOPHILA MELANOGASTER MICROSOMES. MUTAGENICITY WAS OBSERVED IN CHINESE HAMSTER OVARY CELLS, ESCHERICHIA COLI STRAINS 343/113/R-9 AND 343/113/UVRB, AND SALMONELLA TYPHIMURIUM TA 1538. DROSOPHILA MICROSOMES APPEARED TO BE AT LEAST AS ACTIVE AS RAT LIVER MICROSOMES WHEN COMPARED IN THIS TYPE OF MUTAGENICITY TESTING.[BAARS AJ ET AL; MUTAT RES 72 (2): 257-64 (1980)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6777691?dopt=Abstract" target=new>PubMed Abstract</a>
  • COMBINED INTRASANGUINEOUS & URINARY MUTAGENIC ASSAY IN VIVO WAS TESTED WITH DIMETHYLNITROSAMINE, USING SCHIZOSACCHAROMYCES POMBE. DOSE OF 0, 250 AND 405 MG/KG CYCLOPHOSPHAMIDE OR 5, 10, OR 100 MG/KG DIMETHYLNITROSAMINE WERE GIVEN TO MICE AND RATS IMMEDIATELY AFTER THEY WERE INJECTED WITH THE YEAST CELLS. TESTED; LUNG AND KIDNEYS WERE MORE ACTIVE THAN SPLEEN & TESTES. DMNA WAS INACTIVE IN URINE.[BAUER C ET AL; MUTAT RES 74 (4): 291-302 (1980)] **PEER REVIEWED**
  • MALE RATS RECEIVED A SINGLE INJECTION OF DIMETHYLNITROSAMINE (NDMA). SIGNIFICANT INCREASES IN FREQUENCIES OF SISTER CHROMATID EXCHANGES (SCE) IN LYMPHOCYTES & INCIDENCE OF MICRONUCLEATED HEPATOCYTE WERE OBSERVED. NDMA-INDUCED PRECLASTOGENIC DAMAGE IN HEPATOCYTES WAS LOST BETWEEN 28 & 56 DAYS AFTER INJECTION.[TATES AD ET AL; MUTAT RES 107 (1): 131-51 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6828034?dopt=Abstract" target=new>PubMed Abstract</a>
  • WHOLE CELL PREPARATIONS DERIVED FROM COLLAGENASE-TREATED RAT LIVER WERE COCULTIVATED OVERNIGHT WITH STATIONARY CULTURES OF L 5178 Y/TK+/- CELLS IN N-NITROSODIMETHYLAMINE. SUBSTANTIAL DOSE-DEPENDENT INCREASES IN TRIFLUOROTHYMIDINE-RESISTANT VARIANTS WERE OBSERVED AFTER 20 HR TOTAL EXPOSURE TIME.[AMACHER DE, PAILLET SC; MUTAT RES 113 (1): 77-88 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6828044?dopt=Abstract" target=new>PubMed Abstract</a>
  • MUTAGENESIS STUDIES ON DROSOPHILA OOGONIAL CELLS WITH DIMETHYLNITROSAMINE REVEALED HIGH RATES OF SEX-LINKED RECESSIVE LETHALS.[ABRAHAMSON S ET AL; ENVIRON MUTAGEN 5 (6): 891-905 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6653508?dopt=Abstract" target=new>PubMed Abstract</a>
  • CELL-MEDIATED ASSAYS WERE USED TO STUDY ORGAN (LIVER, LUNG, KIDNEY, & BLADDER) & SPECIES (RAT & HAMSTER) SPECIFICITY OF NITROSODIMETHYLAMINE (NDMA) & OTHER CHEMICALS. NDMA WAS HIGHLY ACTIVE IN LIVER CELL-MEDIATED SYSTEM. WITH REGARD TO SPECIES SPECIFICITY, HAMSTER HEPATOCYTES WERE 3-4 TIMES AS ACTIVE AT METABOLIZING NDMA TO MUTAGENIC INTERMEDIATES AS WERE RAT HEPATOCYTES.[LANGENBACH R, NESNOW S; USEPA, RES DEV, (REP) EPA (EPA-600/9-83-008, ORGAN SPECIES SPECIF CHEM CARCINOG; PB83-220137): 377-90 (1983)] **PEER REVIEWED**
  • DNA REPAIR WAS ELICITED BY DIMETHYLNITROSAMINE IN HEPATOCYTES FROM B6C3F1 MICE & SYRIAN HAMSTERS.[MCQUEEN CA ET AL; ENVIRON MUTAGEN 5 (1): 1-8 (1983)] **PEER REVIEWED**
  • ALTERATIONS IN GENE EXPRESSION BY DIMETHYLNITROSAMINE (NDMA) WERE ANALYZED ON 3 UNSTABLE ALLELES OF THE WHITE (W+) LOCUS OF DROSOPHILA MELANOGASTER: WHITE-CREAM (WC); WHITE-IVORY 16 (WI16); & WHITE-UNSTABLE 11 (WU11). THE CMPD APPLIED TOPICALLY DURING THE EARLY LARVAL STAGES INFLUENCED THE DIFFERENT UNSTABLE W ALLELES. THE GENETIC EFFECTS ASSAYED WERE THE ALTERATIONS IN EYE COLOR EITHER WILD-TYPE (W+) OR TO OTHER W MUTANTS, INITIATED BOTH SOMATICALLY & GERMINALLY, AS WELL AS THE SIMULTANEOUSLY INDUCED X-CHROMOSOME RECESSIVE MUTATIONS.[FAHMY MJ, FAHMY OG; CANCER RES 43 (2): 801-7 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6401223?dopt=Abstract" target=new>PubMed Abstract</a>
  • SPONGIOSIS HEPATITIS WAS OBSERVED IN RATS AFTER THE ADMIN OF RELATIVELY LOW DOSES OF DIMETHYLNITROSAMINE. SPONGIOSIS IS A PERSISTING LESION DUE TO SPECIFIC CHANGES OF LIVER CELLS BY HEPATOTROPIC CARCINOGENS.[ZERBAN H, BANNASCH P; CANCER LETT 19 (3): 247-52 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6883311?dopt=Abstract" target=new>PubMed Abstract</a>
  • LIVERS OF GERM-FREE RATS WERE MORE SUSCEPTIBLE TO THE ACUTE TOXIC EFFECTS OF DIMETHYLNITROSAMINE (NDMA) AS WELL AS NDMA + SODIUM NITRITE ADMIN THAN WERE LIVERS OF CONVENTIONAL RATS.[SUMI Y, MIYAKAWA M; CANCER RES 43 (6): 2942-6 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6850604?dopt=Abstract" target=new>PubMed Abstract</a>
  • INDUCTION OF SINGLE-STRAND BREAKS IN THE DNA OF 3 ORGANS OF BD-VI RATS & SYRIAN GOLDEN HAMSTERS WAS EXAM 4 HR AFTER DOSAGE. RATS RECEIVED 40 TO 80 MG/KG IP DOSE OF N-NITROSODIMETHYLAMINE (NDMA) AND HAMSTERS RECEIVED 30 MG/KG NDMA. DNA DAMAGE OCCURRED IN THE LIVER & KIDNEY OF RATS & IN THE LIVER & LUNGS OF HAMSTERS. DAMAGE WAS MONITORED IN VIVO BY ALKALINE ELUTION METHOD, FLUOROMETRICALLY.[BARBIN A ET AL; CARCINOGENESIS (LONDON) 4 (5): 541-5 (1983)] **PEER REVIEWED**
  • NO EVIDENCE OF LIVER NECROSIS WAS OBSERVED AT 24, 48, OR 72 HR AFTER IP INJECTION OF 70 MG/KG INTO PIGEONS. RESISTANCE OF PIGEON LIVER IS RELATED TO ITS LACK TO ACTIVATE NDMA METABOLICALLY.[DIAZ GOMEZ MI ET AL; CANCER LETT 18 (2): 157 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6403221?dopt=Abstract" target=new>PubMed Abstract</a>
  • HOLTZMAN RATS WERE ADMIN SINGLE ORAL DOSES OF N-NITROSODIMETHYLAMINE (NDMA) ON DIFFERENT DAYS OF PREGNANCY. NDMA WAS NOT LETHAL TO PREGNANT RATS UP TO DAY 16 OF PREGNANCY, BUT SINGLE ORAL DOSE OF 15 & 20 MG/KG KILLED 9.4% & 35.3%, RESPECTIVELY, OF RATS TREATED ON DAY 18 OF PREGNANCY. THE ACUTE TOXIC EFFECT OF NDMA WAS GREATER IN PREGNANT THAN IN NONPREGNANT RATS, ESPECIALLY NEAR THE END OF PREGNANCY.[NISHIE K; FOOD CHEM TOXICOL 21 (4): 453-62 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6684627?dopt=Abstract" target=new>PubMed Abstract</a>
  • NAGASE ANALBUMINEMIC RATS (NA) AND NORMAL MALE SPRAGUE-DAWLEY RATS (SD). ANALBUMINEMIC RATS /SRP: A MUTANT STRAIN OF SPRAGUE-DAWLEY RAT/ WERE HIGHLY SUSCEPTIBLE TO INDUCTION OF RENAL TUMORS. AT 6 WEEKS OF AGE, NA-RATS AND SD-RATS RECEIVED A SINGLE INTRAPERITONEAL INJECTION OF DMN AT 50 MG/KG. THIRTY-NINE WEEKS AFTER N-DIMETHYLNITROSAMINE ADMIN, THE INCIDENCE OF RENAL TUMORS & AVG WT OF KIDNEYS (INCLUDING TUMORS) WERE 76% & 10.8 G IN ANALBUMINEMIC RATS, RESPECTIVELY, WHEREAS THEY WERE 37.1% & 3.5 G, RESPECTIVELY, IN NORMAL MALE SPRAGUE-DAWLEY RATS.[NAGASE S ET AL; GANN 74 (3): 317-8 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6884689?dopt=Abstract" target=new>PubMed Abstract</a>
  • RATS WERE GIVEN A SINGLE DOSE OF 200 MG/KG N-NITROSODIETHYLAMINE (DEN) AND 2 WK LATER WERE TREATED WITH VARIOUS TEST COMPOUNDS FOR 6 OR 10 WK. IN TESTS ON DOSE-DEPENDENT EFFECTS OF PROMOTING AGENTS, DIMETHYLNITROSAMINE (NDMA) WAS GIVEN AT DIFFERENT CONCENTRATIONS FOR 6 WK AFTER N-NITROSODIETHYLAMINE TREATMENT. CLEAR DOSE-DEPENDENT EFFECTS OF NDMA WERE SEEN IN INDUCTION OF GAMMA-GLUTAMYL TRANSPEPTIDASE POSITIVE FOCI IN THE SHORT-TERM EXPERIMENT & NEOPLASTIC LESIONS IN THE LONG-TERM ONE.[ITO N ET AL; ENVIRON HEALTH PERSPECT 50: 131-8 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6191977?dopt=Abstract" target=new>PubMed Abstract</a>
  • N-NITROSODIMETHYLAMINE AT 50PPM INDUCED HEPATOMAS IN BRACHYDANIO RERIO (FISH) EXPOSED FOR 22-23 WK.[AYDIN NE, BULAY OM; DOGA SERI C 7 (1): 1-7 (1983)] **PEER REVIEWED**
  • TOXIC EFFECTS OF N-NITROSODIMETHYLAMINE (NDMA) WERE STUDIED BY LIGHT & ELECTRON MICROSCOPY AFTER INJECTION INTO THE FOOT OF MUSSELS. ONE INJECTION OF NDMA AT 0.1, 0.2, 0.4, & 0.8 MG/MUSSEL PRODUCED, WITHIN 15 DAYS EXTENSIVE INFLAMMATORY REACTIONS IN THE SUPPORTING LEYDIG CELL TISSUE IN THE DIGESTIVE DIVERTICULA, NECROSIS OF THE EPITHELIUM LINING, THE DIGESTIVE TUBULES, & NECROSIS OF GERMINAL EPITHELIUM LINING THE GENITAL FOLLICLES. 8 WEEKLY INJECTIONS OF 0.2 MG, EXAM FOR 3O WK PRODUCED EXTENSIVE COLLAGENOUS SCAR TISSUE FORMATION BETWEEN THE TUBULES OF THE DIGESTIVE DIVERTICULA, PRESENCE OF NUMEROUS GRANULOCYTOMAS, & NECROSIS OF THE GERMINAL EPITHELIUM OF THE GENITAL FOLLICLES.[RASMUSSEN LP D ET AL; AQUAT TOXICOL 3 (4): 285-99 (1983)] **PEER REVIEWED**
  • Shasta strain of rainbow trout were fed N-nitrosodimethylamine in the diet for 52 weeks. After this time the fish were placed on a control diet for an additional 26 weeks. No hepatocellular carcinomas were detected at 26 weeks after feeding of the nitrosamine began. At 52 weeks, however, a direct dose-related response of hepatocellular carcinoma occurred in trout fed 200, 400, and 800 mg dimethylnitrosamine/kg. A greater incidence of carcinomas was observed at 78 weeks, even though feeding was discontinued after 52 weeks.[USEPA; Ambient Water Quality Criteria Doc: Nitrosamines p.1127 (1980) EPA-440/5-80-064] **PEER REVIEWED**
  • Of the 107 N-nitroso compounds (including 83 N-nitrosamines) listed, 87 (including 67 N-nitrosamines) are reported as having carcinogenic activity. Since that time more compounds have been tested and, to date, approximately 100 N-nitroso compounds are known to be carcinogenic in one or more species of experimental animals. /N-Nitrosamines/[USEPA; Ambient Water Quality Criteria Doc: Nitrosamines p.C-26 (1980) EPA-440/5-80-064] **PEER REVIEWED**
  • Single doses of DMNA (dimethylnitrosamine) from 8 to 15 mg/kg body weight were given to 37 foxes. The course and intensity of the disease was not influenced by the application route, but was directly related to the amount of DMNA given per kg body weight, causing hemorrhagic centrolobular liver necrosis and acute vessel changes. ... The LD50 determined after 4 wk was 10 mg DMNA/kg body weight In a longer experiment 18 foxes in 3 groups were given 2 weekly doses of DMNA in food. They were treated with daily estimated doses of 1.0, 0.2 and 0.1 mg DMNA/kg body weight, respectively. The foxes in groups 1 and 2 developed ascites, jaundice, and liver failure after intake of 45-70 mg DMNA/kg body weight. The foxes treated with 1 mg DMNA/kg body weight showed centrolobular hemorrhagic liver necrosis and productive vessel changes in the hepatic vein system. The second group given 0.2 mg DMNA/kg body weight developed hemorrhagic centrolobular necrosis which healed with fibrosis leading to cirrhosis and chronic occlusion in many hepatic veins. Noduli of chondroid lamellae and foci of hematopoietic tissue and early stages of hemagiomatous liver tumors were found in the liver. The group exposed to 0.1 mg of DMNA/kg body weight/day developed thickening in the walls of the hepatic veins. After more than 3.5 yr of exposure, multiple hemangiosarcomas grew out from the changed vessel walls. In a shorter experiment with daily DMNA doses in the feed below 0.165 mg/kg body weight, all the foxes were completely healthy and only some showed beginning changes in the hepatic vein walls. Hematomas were often seen in foxes dying after a single DMNA dose. One fox treated with 0.1 mg DMNA/kg body weight died of brain bleeding after 220 days of treatment. Chronic vessel changes were found in the heart and kidneys of the DMNA treated foxes. DMNA produces vessel changes of a more general nature.[Koppang N et al; Acta Vet Scand 22 (3-4): 501-16 (1982)] **PEER REVIEWED**
  • ... In vitro RNA synthesis and methylation were proportional to time and nuclear concentration and dependent on exogenous nucleoside triphosphates and S-adenosylmethionine. Of the in vitro synthesis, 60-70% was inhibited by 1 ug/ml alpha-amanitin. Total liver nuclear RNA systhesis was increased after dimethylnitrosamine exposure but, unlike RNA synthesis in nuclei after partial hepatectomy, alpha-amanitin sensitive and resistant synthesis were increased. Differences were found between dimethylnitrosamine-treated liver and kidney nuclear RNA synthesis which was sensitive to inhibition by 1-10 ug/ml alpha-amanitin, presumably a product of RNA polymerase III. Nuclear RNA methylation with S-adenosylmethionine, which was dependent on new RNA synthesis, differed between dimethylnitrosamine-treated rat liver and kidney nuclei. The endogenous RNA methyl substituents labeled in vitro showed differences in levels of methylation of bases, the 2'-O position of ribose and caps in comparisons between control and dimethylnitrosamine-treated nuclei from liver and kidney. Significant differences were obtained in nuclear RNA transcription and methylation in vitro between the 2 tissues in response to pretreatment of the rat in vitro with dimethylnitrosamine.[Winicov I; Biochim Biophys Acta 654 (1): 31-41 (1981)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6168289?dopt=Abstract" target=new>PubMed Abstract</a>
  • Although N-nitrosamines are rapidly and fairly evenly distributed throughout the bodies of rats after injection, the acute toxic damage they produce is more severe in the liver than elsewhere, and tumors following chronic exposure are confined mainly to the liver and kidney. /N-Nitrosamines/[USEPA; Ambient Water Quality Criteria Doc: Nitrosamines p.C-41 (1980) EPA-440/5-80-064] **PEER REVIEWED**
  • Many N-nitrosamines are teratogenic, mutagenic, and carcinogenic. Evidence from experimental animals suggests that, as carcinogens, they are /effective by all routes of administration/. However, some are capable of inducing tumors after a single dose, and they are also capable of inducing tumors in certain organs and tissues regardless of the route of administration, ie, they are systemic carcinogens. /N-Nitrosamines/[USEPA; Ambient Water Quality Criteria Doc: Nitrosamines p.C-42 (1980) EPA-440/5-80-064] **PEER REVIEWED**
  • All animal species are susceptible to carcinogenesis induced by N-nitroso compounds, including nitrosamines. /Nitrosamines and other N-nitroso carcinogens/[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 513] **PEER REVIEWED**
  • Dimethylnitrosamine given on the last day of pregnancy produced only a few uncharacteristic tumors. Dimethylnitrosamine was not teratogenic in rats when 30 mg was given orally in single days during gestation.[Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 199] **PEER REVIEWED**
  • Deuterated and non-deuterated N-nitrosodimethylamine, epichlorohydrin and dimethyl sulfate were evaluated for the ability to induce DNA single-strand breaks in rat hepatocytes as measured by alkaline elution. Non-deuterated nitrosodimethylamine induced twice the amount of DNA-strand breaks as the deuterated form. No evidence of a deuterium isotope effect was seen for the direct-acting alkylating agents epichlorohydrin and dimethyl sulfate.[Sargent EV et al; Mutation Res 263 (1): 9-12 (1991)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2034243?dopt=Abstract" target=new>PubMed Abstract</a>
  • IN ALKALINE CONDITIONS (PH 12.5), THE REDUCED VISCOSITY OF KIDNEY & LUNG DNA FROM CONTROL RATS INCR SLOWLY WITH TIME REACHING MAX AFTER 9-12 HR. CARCINOGENS, BY INDUCING DNA STRAND BREAKS EITHER CHEMICALLY OR INDIRECTLY BY EXCISION REPAIR OR DURING INCUBATION IN ALKALI, CAUSE A REDN OF DNA SUPERCOILING WHICH CAN BE SENSITIVELY MEASURED BY MONITORING CHANGES IN VISCOSITY. COMPUTERIZED ANALYSES OF TIME-VISCOSITY CURVES SHOWED 95% OF ITS MAX VALUE (T-95) WAS INDUCED BY IP DOSES OF N-NITROSODIMETHYLAMINE: KIDNEY 0.07 MG/KG, LUNG 0.28 MG/KG. THE DECREASE IN T-95 WAS DOSE-RELATED.[CARLO P ET AL; CARCINOGENESIS 4 (2): 137-40 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6825203?dopt=Abstract" target=new>PubMed Abstract</a>
  • VISCOMETRIC ASSAY OF DNA DAMAGE IN RAT LIVER AFTER SINGLE IP DOSES OF N-NITROSODIMETHYLAMINE (0.07 MG/KG) REVEALED THE TIME REQUIRED FOR DNA REDUCED VISCOSITY TO REACH ITS MAXIMUM VALUE WAS SIGNIFICANTLY REDUCED.[BRAMBILLA G ET AL; CANCER RES 43 (1): 202-9 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6847769?dopt=Abstract" target=new>PubMed Abstract</a>
  • THE INDIRECT-ACTING ALKYLATING AGENT, DIMETHYLNITROSAMINE INDUCED DNA DAMAGE ONLY WHEN NADPH GENERATING SYSTEM WAS INCLUDED IN THE INCUBATION MIXTURE.[COHEN AM, PRABHAKAR H; CANCER LETT 18 (2): 163-7 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6831392?dopt=Abstract" target=new>PubMed Abstract</a>
  • STRUCTURAL ANALYSES BY CHROMATOGRAPHY ON BENZOYLATED-DEAE-CELLULOSE WAS MADE OF HEPATIC DNA FROM RATS TREATED IP DAILY (1 MG/KG) FOR UP TO 21 WK WITH DIMETHYLNITROSAMINE (NDMA). THE PROPORTION OF DNA RETAINED INCREASED. IN THE COURSE OF CHRONIC ADMIN INCREASING TIME IS REQUIRED TO COMPLETE DNA REPAIR PROCESSES OPERATIVE IN RAT LIVER.[KOSIC J, STEWART BW; CANCER LETT 20 (1): 5-12 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6318966?dopt=Abstract" target=new>PubMed Abstract</a>
  • A SINGLE ADMIN OF 50 MG N-NITROSODIMETHYLAMINE/KG REDUCED THE TOTAL PROTEIN CONTENT IN THE HEPATIC MICROSOMES OF RATS. IT REDUCED PROTEIN SYNTHESIS, PARTICULARLY AT THE TRANSLATIONAL LEVEL, & THIRDLY ITS INTERACTION WITH CELL MEMBRANE LIPID COMPONENTS RESULTED IN THE DISINTEGRATION & CONFORMATIONAL CHARGES IN MEMBRANE-BOUND PROTEINS.[TUTELYAN VA, LASHNEVA NV; FARMAKOL TOKSIKOL (MOSCOW) 46 (2): 111-4 (1983)] **PEER REVIEWED**
  • The product(s) of metabolism of N-nitrosamines are thought to be responsible for the mutagenicity and/or carcinogenicity of many of these compounds. One hypothesis is that these active intermediates alkylate DNA at specific sites. Although the liver appears to be the major site of decomposition, other organs, such as kidney and lung, possess varying capacity to metabolize nitrosamines. The relative metabolic activity of different organs toward the same compound varies among species. /Nitrosamines/[USEPA; Ambient Water Quality Criteria Doc: Nitrosamines p.C-23 (1980) EPA-440/5-80-064] **PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LC50 Rat inhalation 78 ppm/4 hr[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1128] **PEER REVIEWED**
  • LC50 Mouse inhalation 57 ppm/4 hr[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1128] **PEER REVIEWED**
  • Ip LD50 rat = 34 mg/kg[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1140] **PEER REVIEWED**
  • LD50 Rat oral 27-41 mg/kg[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1128] **PEER REVIEWED**

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Absorption, Distribution and Excretion

  • IT IS ABSORBED FROM GASTROINTESTINAL TRACT & LUNG ... SKIN ABSORPTION IS SLOW. WHEN ADMINISTERED TO RATS, MICE, & RABBITS, IT IS DISTRIBUTED UNIFORMLY IN TISSUE ... ALTHOUGH THE LIVER IS MAIN ORGAN CONCERNED WITH ITS METABOLISM & IS SITE OF SELECTIVE TOXICITY, DIMETHYLNITROSAMINE DOES NOT CONCENTRATE THERE. ONLY A SMALL PERCENTAGE IS EXCRETED UNCHANGED IN RAT URINE AFTER ORAL & IV DOSES OF 50 TO 100 MG/KG. A LARGE PROPORTION ... APPEARS IN THE EXPIRED AIR AS ... CARBON DIOXIDE (APPROX 60% IN 24 HR).[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 2787] **PEER REVIEWED**
  • N-NITROSODIMETHYLAMINE (NDMA) REACHED EQUAL MAX CONCN IN THE MATERNAL & FETAL BLOOD & TISSUES WITHIN 5-15 MIN & 30-60 MIN, RESPECTIVELY, AFTER AN IV INJECTION OF 50 MG/KG INTO MICE & RATS ON DAYS 21-23 OF PREGNANCY. THE SUBSEQUENT EXPONENTIAL DECR IN NDMA WAS MORE RAPID IN MICE THAN IN RATS. INCREASING THE NDMA LEVEL IN MATERNAL BLOOD BY INCREASED DOSES, LINEARLY INCREASED THE FETAL BLOOD NDMA TO A PEAK OF 120 MUG/ML IN MICE & 220 UG/ML IN RATS, WHEREAS THE LEVEL OF NDMA IN MATERNAL BLOOD CONTINUED TO INCREASE AS DOSES WERE INCREASED TO 300 MG/KG.[SHENDRIKOVA IA ET AL; FARMAKOL TOKSIKOL (MOSCOW) 46 (6): 53-7 (1983)] **PEER REVIEWED**
  • N-Nitrosodimethylamine (DMN) was shown to be assimilated by the roots and translocated to the tops of lettuce and spinach plants.[Dean-Raymond D, Alexander M; Nature 262: 394-6 (1976)] **PEER REVIEWED**
  • The acute toxicities of dimethylnitrosamine and diethylnitrosamine were evaluated in adult male crayfish. Toxicokinetic studies of (14)C dimethylnitrosamine and (14)C diethylnitrosamine in Austropotamobius pallipes (crayfish), administered by iv injection, show high concns of (14)C in abdominal muscle and hepatopancreas. Excretion is greater with dimethylnitrosamine, and retention in tissues, especially the hepatopancreas, is greater with diethylnitrosamine.[Alibaud R et al; Xenobiotica 15 (12): 1103-10 (1985)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/4090529?dopt=Abstract" target=new>PubMed Abstract</a>

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Metabolism/Metabolites

  • FORMATION OF N-NITROSODIMETHYLAMINE (NDMA) IN THE STOMACHS OF RATS & MICE AFTER SIMULTANEOUS ORAL ADMIN OF (14)C-LABELED DIMETHYLAMINE & POTASSIUM NITRITE WAS DETERMINED BY MEASURING THE METHYLATION OF LIVER DNA. SIMULTANEOUS ADMIN OF 50 MG ASCORBATE/KG INHIBITED THE NITROSATION BY APPROX 80%. 50 MG ALPHA-TOCOPHEROL ACETATE/KG REDUCED THE NITROSATION BY APPROX 50%.[MEIER-BRATSCHI A ET AL; FOOD CHEM TOXICOL 21 (3): 285-9 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6683225?dopt=Abstract" target=new>PubMed Abstract</a>
  • A METHOD FOR QUANTITATIVE ESTIMATION OF THE FORMATION OF N-NITROSODIMETHYLAMINE (NDMA) IN MICE WAS DEVELOPED. WHEN 0.25 UMOLE OF AMINOPYRINE & 0.25-2.0 UMOLE OF SODIUM NITRITE WERE SIMULTANEOUSLY ADMIN ORALLY TO MICE, THE AMT OF NDMA FORMED IN 20 MIN WAS 8.2-60.3 NMOL. THESE VALUES ARE EQUAL TO APPROX 30-200 UG/KG OF BODY WT WHICH ARE NEARLY DAILY DOSES EXPECTED TO CAUSE CARCINOGENIC EFFECT IN MICE OR RATS.[KAWANISHI T ET AL; ARCH TOXICOL 54 (4): 323-30 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6667123?dopt=Abstract" target=new>PubMed Abstract</a>
  • AVAIL EVIDENCE SUGGESTS THAT NDMA REQUIRES METABOLIC ACTIVATION TO EXERT ITS TOXIC & CARCINOGENIC EFFECTS. RATE OF METAB ... IN VIVO HAS BEEN EXAM BY MEASURING RATE OF LOSS OF NDMA FROM BLOOD & EXHALATION OF (14)CO2 FOLLOWING ADMIN OF (14)C-NDMA. IN RATS ... 30 MG/KG ADMIN BY IP INJECTION IS METABOLIZED WITHIN 6 HR. RATE OF METAB OF NDMA IN VITRO ... MEASURED BY USE OF SLICES OF LIVER & OTHER ORGANS ... FROM RATS, HAMSTERS, MONKEYS, TROUT, GOLDFISH & VARIOUS AMPHIBIANS. ... OXIDATIVE N-DEMETHYLATION TO FORM FORMALDEHYDE HAS BEEN DEMONSTRATED WITH LIVER MICROSOMES FROM RATS, MICE & HAMSTERS. MICROSOMAL OXIDN HAS BEEN SUGGESTED TO RESULT IN UNSTABLE N-NITROSO-N-METHYL-N-HYDROXYMETHYLAMINE, WHICH DECOMP TO YIELD METHYLATING SPECIES & FORMALDEHYDE ...[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/index.php, p. V17 146 (1978)] **PEER REVIEWED**
  • ... IN THE METABOLISM ... ONE OF THE INTERMEDIARY PRODUCTS IS DIAZOMETHANE.[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 621] **PEER REVIEWED**
  • NITROSODIMETHYLAMINE (NDMA) & 2 OF ITS METABOLITES, METHYLHYDRAZINE & 1,1-DIMETHYLHYDRAZINE, WERE METABOLIZED TO CARBON DIOXIDE BY LIVER SLICES OBTAINED FROM RATS. RAT LIVER MICROSOMES OR 9,000XG SUPERNATANTS TRANSFORMED NDMA TO FORMALDEHYDE. NDMA LED TO COVALENT BINDING TO PROTEINS IN INCUBATION MIXTURES CONTAINING MICROSOMES OR 9,000XG SUPERNATANTS. IN THE CASE OF NDMA, THE PROCESS WAS ENZYMIC & REQUIRED NADPH IN BOTH CELLULAR FRACTIONS.[GODOY HM ET AL; J NATL CANCER INST 71 (5): 1047-51 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6580481?dopt=Abstract" target=new>PubMed Abstract</a>
  • MAXIMAL RATES OF METABOLIC OXIDATION OF N-NITROSODIMETHYLAMINE (NDMA) & NDMA-D6 IN VIVO WERE MEASURED BY FOLLOWING (14)CO2 EXHALATION IN RATS AFTER IP INJECTION OF 2 (14)C-LABELED CARCINOGENS AT DOSES OF 20 OR 40 MG/KG. COMPLETE DEUTERATION OF NDMA REDUCED ONLY SLIGHTLY THE MAXIMAL RATE OF METABOLISM WHEN THE 2 SUBSTRATES WERE ADMIN SEPARATELY. HOWEVER, MUCH LARGER DEUTERIUM ISOTOPE EFFECTS WERE OBSERVED WHEN MIXTURES OF NDMA WITH NDMA-D6 WERE INJECTED. THESE RESULTS ARE TENTATIVELY INTERPRETED AS EVIDENCE THAT C-H BOND CLEAVAGE IS NOT A RATE-LIMITING FEATURE OF OVERALL METABOLISM, BUT THAT THE COMPLEX BETWEEN NDMA & THE PRINCIPAL ENZYME(S) METABOLIZING IT IN VIVO FREELY EQUILIBRATES WITH UNBOUND SUBSTRATE.[SWANN PF ET AL; CARCINOGENESIS (LONDON) 4 (7): 821-5 (1983)] **PEER REVIEWED**
  • Highly purified NADPH-cytochrome p450 reductase and the other major forms of cytochrome p450 induced by phenobarbital and beta-naphthoflavone were used in reconsitituted systems to study the demethylation and activation of dimethylnitrosamine to mutagenic intermediates. Both forms of cytrochrome p450 were active in the demethylation of dimethylnitrosamine, but cytochrome p450 from phenobarbital treated rats was more active and produced nearly twice as much formaldehyde per mole of hemoprotein.[Masson HA et al; Toxicol Lett 17 (1-2): 131-5 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6414108?dopt=Abstract" target=new>PubMed Abstract</a>
  • THE DEMETHYLATION OF NDMA BY RAT HEPATIC MICROSOMES WAS NOT CHANGED BY PRETREATMENT WITH PHENOBARBITAL & METHYLCHOLANTHRENE.[KAWANISHI T ET AL; CANCER LETT (SHANNON, IREL) 20 (2): 157-64 (1983)] **PEER REVIEWED**
  • FASTING FOR 1-3 DAYS CAUSES A 2- OR 3-FOLD ENHANCEMENT OF THE REDUCED NADP-DEPENDENT NITROSODIMETHYLAMINE DEMETHYLASE (NDMAD) ACTIVITY. THE CYTOCHROME P450 (P450) CONTENT & ACTIVITIES OF REDUCED NADP P450 REDUCTASE & BENZPHETAMINE DEMETHYLASE, HOWEVER, ARE ONLY MODESTLY INCREASED. ELECTROPHORETIC ANALYSIS REVEALED THE INDUCTION OF A 50,000-DALTON PROTEIN BAND DURING FASTING.[TU YY, YANG CS; CANCER RES 43 (2): 623-9 (1983)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/6401221?dopt=Abstract" target=new>PubMed Abstract</a>
  • DNA BREAKS INDUCED BY DIMETHYLNITROSAMINE IN CULTURED LIVER CELLS WERE MORE DETECTABLE FROM RAT TREATED WITH PHENOBARBITAL. TREATMENT FOR 24 HR WITH 60 & 13.5 UMOLAR DIMETHYLNITROSAMINE (NDMA) OF HEPATOCYTES FROM UNTREATED & PHENOBARBITAL TREATED RATS, RESPECTIVELY, DECREASED THE MOLECULAR WT OF DNA BY 50%. IT IS MORE GENOTOXIC FOR HEPATOCYTES FROM PHENOBARBITAL-TREATED RATS, PROBABLY DUE TO AUGUMENTED METABOLISM OF NDMA BY THESE CULTURES.[MENDOZA-FIGUEROA T ET AL; TOXICOL 27 (1): 55-69 (1983)] **PEER REVIEWED**
  • Metabolites identified inexcreta /from Austropotamobius pallipes, crayfish/ include monomethylnitrosamine from dimethylnitrosamine, and (hydroxyethyl)ethyl, bis(hydroxyethyl), and (carboxyethyl)ethylnitrosamine from diethylnitrosamine.[Alibaud R et al; Xenobiotica 15 (12): 1103-10 (1985)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/4090529?dopt=Abstract" target=new>PubMed Abstract</a>
  • ... Reduction of nitrate to nitrite /in the gastrointestinal tract/ permits the formation of highly carcinogenic nitrosamines by reaction with secondary amines from the diet. /Nitrosamines/[National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 33] **PEER REVIEWED**
  • The metabolism of N-nitrosodimethylamine by liver microsomes from acetone-induced rats as well as by a reconstituted system containing purified cytochrome p450IIE1 was examined. The products consisted of methylamine, formaldehyde, methanol, methylphosphate and formic acid from N-nitrosodimethylamine. Compared to liver microsomes from untreated rats, the metabolic activity of acetone induced microsomes was approximately 4 times higher for N-nitrosodimethylamine. Using the reconstituted system, the enzyme activities (nmol substrate metabolized/nmol p450/min) N-nitrosodimethylamine was 9.47. Incubations carried out in the presence of a monoclonal antibody to cytochrome p450IIE1 resulted in a 85-90% inhibition in this system. The results indicate that N-nitrosodimethylamine is metabolized by the same form of rat liver cytochrome p450. The stoichiometry of N-nitrosodimethylamine products formed in these reactions indicates that denitrosation, a presumed detoxication process, and alpha-hydroxylation, an activation reaction, are also catalyzed by the same cytochrome p450 isozyme.[Sohn OS et al; Carcinogenesis 12 (1): 127-31 (1991)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/1988172?dopt=Abstract" target=new>PubMed Abstract</a>
  • A study was conducted on the mechanism by which hepatic N-nitrosodimethylamine demethylase, also known as cytochrome p450-IIE1, is induced by acetone treatment in the rat. Acetone was fed at a concentration of 5% volume/volume in drinking water to male Sprague-Dawley rats for at least 10 days before experiments. Tritiated leucine was given to some animals, which were killed 3, 8 or 15 minutes later to measure the rate of synthesis of N-nitrosodimethylamine demethylase. Another group of animals received (14)C labeled acetate and were killed at 21, 24, 48 and 72 hours later for determination of the rate of degradation of N-nitrosodimethylamine demethylase. N-nitrosodimethylamine demethylase was purified from solubilized liver microsomal protein by an immunoaffinity column coupled to mouse monocolonal antibody raised against N-nitrosodimetylamine demethylase. Acetone treatment did not alter the rate of synthesis of N-nitrosodimethylamine demethylase. In control rats, the degradation of N-nitrosodimethylamine demethylase was biphasic, with the fast and slow phases having half-lives of approximately 7 and 37 hours, respectively. In rats given acetone, the degradation curve for labeled N-nitrosodimethylamine demethylase showed only one phase, corresponding to the slower one in control rats. The mechanism for the acetone induction of N-nitrosodimethylamine demethylase is that acetone stabilizes the N-nitrosodimethylamine demethylase protein, thereby slowing its degradation.[Song BJ et al; J Biological Chem 264 (6): 3568-72 (1989)] **PEER REVIEWED**
  • The metabolism of N-nitrosodimethylamine was investigated in incubations with human liver microsomes from alcoholics and control patients who suffered from other diseases, but had a histological normal liver. All of the microsomal samples studied were able to metabolize N-nitrosodimethylamine at various concentrations to both formaldehyde and nitrite. Analysis of the liver microsomes from alcoholics revealed that both enzymatic activities, formaldyhyde and nitrite formation, were enhanced several times as compared to the control patients. Alcoholics metabolize N-nitrosodimethylamine at a higher rate probably due to the induction of one or more ethanol-inducible human liver cytochromes p450.[Amelizad S et al; Cancer Letters 46 (1): 43-9 (1989)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2736507?dopt=Abstract" target=new>PubMed Abstract</a>
  • The metabolic activation of N-nitrosodimethylamine to an active metabolite is important in its carcinogenic effect. The lung and liver were compared for their responses to the induction of N-nitrosodimethylamine demethylation by 10% ethanol in the drinking water and by repeated bolus injections. Ethanol in the drinking water increased NDMA metabolism several-fold in both the liver and the lung. Repeated ip injections with 0.6 and 3.0 ml ethanol/kg for 7 days also enhanced this activity in a dose-dependent fashion. These results suggest that in the lung, as in the liver, ethanol may influence the metabolic activation of this nitrosamine.[Carlson GP; Cancer Letters 54 (3): 153-6 (1990)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/pubmed/2224843?dopt=Abstract" target=new>PubMed Abstract</a>
  • The product(s) of metabolism of N-nitrosamines are thought to be responsible for the mutagenicity and/or carcinogenicity of many of these compounds. One hypothesis is that these active intermediates alkylate DNA at specific sites. Although the liver appears to be the major site of decomposition, other organs, such as kidney and lung, possess varying capacity to metabolize nitrosamines. The relative metabolic activity of different organs toward the same compound varies among species. /Nitrosamines/[USEPA; Ambient Water Quality Criteria Doc: Nitrosamines p.C-23 (1980) EPA-440/5-80-064] **PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 11/28/2012.

The NTP is administratively located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.

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