N-Nitrosodimethylamine

More recent studies have shown that 10-day gavage treatment of rats with up to 2 mmol/kg 2-nitropropane caused an increased incidence of cell proliferation similar treatment with the noncarcinogenic isomer 1-nitropropane did not cause an increase in cell proliferation.  

The lARC has determined that there is sufficient evidence for carcinogenicity of 2-nitropropane in experimental animals and that it is possibly carcinogenic to humans.  

2-Nitropropane is genotoxic in a variety of assays including the kmes Salmonella assay, in vitro sister chromatid exchange, and chromosome aberrations and unscheduled DNA synthesis assay.  

Although the early literature stated that the odor threshold was above 80 ppm and therefore not capable of providing adequate warning of exposure, a more recent study has determined that a lower threshold of approximately 5 ppm exists that should provide some warning of exposure, especially if workers are familiarized with the odor.  

The 2003 ACGIH threshold limit valuetime-weighted average (TLV-TWA) for 2-nitropropane is 10 ppm (36mg/m ) with an A2-suspected human carcinogen designation. 

Severe poison.2 Has caused fatal liver disease in humans.3 Animal carcinogen reasonably anticipated to be a human carcinogen.4 Exposure by all routes should be carefully controlled to the lowest possible levels.2 

Wear nitrile rubber gloves, eye protection or all-purpose canister respirator, and laboratory coat. Cover spill with a 1 1 1 mixture by weight of sodium carbonate or calcium carbonate, clay cat litter (bentonite), and sand. Scoop the mixture into an appropriately labeled container for disposal by burning (see Waste Disposal).2,5 

Package Lots. Place in a separate labeled container for recycling or disposal by burning.2 

Gram Quantities. Work in the fume hood. Wear nitrile rubber gloves, eye protection, and laboratory coat. Prepare a solution of 0.05 mol (3.7 g, 3.7 mL) of the N-nitrosodimethylamine in 500 mL of water in a 2-L, three-necked, round-bottom flask 

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N Nitrosodimethylamine (formed dunng tanning of leather also found in beer and herbicides)... 

N-Nilrosoamines are reduced easily lo ihe hydrazine and, if continued, lo the amine (62). Early workers ruled out cleavage of dimeihylhydrazine as the source of dimethylamine in hydrogenation of N-nitrosodimethylamine since liule ammonia was found the letramethylietrazene was implicated in the hydrogenolysis (fSI). Palladium-on-carbon under mild conditions is used for industrial production of dialkyl hydrazines from N-nitrosoamines. 

There is evidence that N-nitrosodimethylamine can be among its oxidation products (1,- ) but, other than studies of the gas phase... 

Dark Reaction of UDMH with Oq. When O3 was injected into UDMH-air mixtures, consumption of UDMH and O3 was "instantaneous" and formation of N-nitrosodimethylamine was immediately observed. The reaction was complete within 2 minutes, by which time either the hydrazine or the O3 was totally consumed. Figure 1 shows IR spectra before and 2 minutes after -2 ppm of O3 was injected into air containing -2 ppm of UDMH. The nitrosamine is positively identified by its IR absorptions at 1296, 1016, and 848 cm . ... 

Dark Decay of UDMH in the Presence of NO, When 1.3 ppm of UDMH in air was reacted in the dark with an approximately equal amount of NO, 0.25 ppm of UDMH was consumed and formation of -0.16 ppm HONO and -0.07 ppm N2O was observed after -3 hours. Throughout the reaction, a broad infrared absorption at -988 cm" corresponding to an unidentified product(s), progressively grew in intensity. The residual infrared spectrum of the unknown product(s) is shown in Figure 2a. It is possible that a very small amount (50.03 ppm) of N-nitrosodimethylamine could also have been formed but the interference by the absorptions of the unknown product(s) made nitrosamine (as well as nitramine) detection difficult. No significant increase in NH3 levels was observed, in contrast to the UDMH dark decay in the absence of NO. Approximately 70% of the UDMH remained at the end of the 3-hour reaction period this corresponds to a half-life of -9 hours which is essentially the same decay rate as that observed in the absence of NO. 

The results of the study reported here show clearly that, upon release into the atmosphere, N,N-dlmethylhydrazlne (UDMH) can be rapidly converted to N-nitrosodimethylamine by its reaction with atmospheric ozone. A similar conclusion can be reached concerning nitrosamine formation from other unsymmetrically disubstituted hydrazines ... 

In 1976, Ross al. first reported that the powerful carcinogens, N-nitrosodimethylamine (NOMA) and N-nitrosodi-n-propyl-amine (NDPA) were found at parts per million (ppm) concentrations in certain commercial herbicide formulations (1., ). Since then, scientists have learned that carcinogenic N-nitroso compounds can be formed in a wide variety of media of interest to those who manufacture, use, or study pesticide products. Some of these nitrosation-supporting media are listed in Table I. 

An attempt to estimate human daily impact of N nitroso compounds is shown in Table I. The apparent intake from food of preformed nitrosamines is comparatively low, at least in these surveys of a Western diet in England (3). The Intake directly to the respiratory tract from smoking could be somewhat larger. However, if the blood levels reported are confirmed as correct, then inputs of up to 700 meg per day of at least N nitrosodimethylamine (NDMA) may be calculated, based on pharmacokinetic considerations of data obtained in animals and extrapolated to man. It should be emphasized that no information is available at present on nitrosamide intake or in vivo formation, largely because of analytical limitations. 

The complex pattern of human exposure to environmental N-nitroso compounds is summarized. Recent results are given in three areas, where a significant reduction of human exposure has been achieved after elucidation of its causes 1, N-Nitrosodimethylamine in beer. 2, Volatile N-nitrosamines in baby nipples and pacifiers and 3. occupational exposure in the rubber industry. 

We have previously shown in a survey on the occurence of volatile nitrosamines in commercial food of the German market that beer is the most important source of N-nitrosodimethylamine (NDMA) (Spiegelhalder et al, 1979 Preussmann et al., 1980 Spiegelhalder et al, 1980) The investigation of about 3000 food samples allowed the calculation of an average daily intake of 1.1 /ug NDMA and of 0.1-0.15/ig N-nitrosopyrrolidine (NPYR) for a male adult in the year 1978. For NDMA 64% (= 0.7yug/day) of the total daily intake resulted from the consumption of beer. 

NDMA = N-nitrosodimethylamine NDEA N-nitrosodiethylcunine NDBA = N-nitroso-dibutylamine NPIP = N-nitrosopiperidine NMPhA = N-nitrosomethylphenylamine... 

N-Nitrosodimethylamine (NDMA) levels in malt and beer have been significantly reduced, and methods for the inhibition of NDMA formation are discussed. 

Since the first report of N-nitrosodimethylamine (NDMA) contamination in beer (ij ), there have been a number of surveys on volatile nitrosamine occurrence in beers of different types and origins. The data in Table I includes NDMA analyses on light beers, dark beers, ales, and malt liquors. Table I shows that the... 

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