N-Nitrosonornicotine

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for N-NITROSONORNICOTINE (7 total), please visit the HSDB record page.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. The completeness of the cleaning procedures should be considered before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at the end of shift, but should remain at employee's place of work for cleaning.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for N-NITROSONORNICOTINE (10 total), please visit the HSDB record page.

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves.

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

The saliva of long term oral snuff users has been found to contain N-nitrosonornicotine levels of 0.003 to 0.4 ug/g(1). The saliva of tobacco chewers had levels of 16.5 to 59.7 ng/mL(1). N-Nitrosonornicotine was not detected in the combined gastric juices of 14 volunteers who each smoked 28 cigarettes per day(1).

Previous studies indicate that Herpes simplex virus enhances the carcinogenic activity of smokeless tobacco and tobacco related chemical carcinogens in animals. Since tobacco specific N'-nitrosamines such as N'-nitrosonornicotine and 4-(N-methyl-N'-nitrosamino)-1-(3-pyridyl)-1-butanone are major chemical carcinogens of smokeless tobacco and are known to be responsible for the development of oral cancers in smokeless tobacco users, the combined effects of tobacco specific N'-nitrosamines and Herpes simplex virus in cell transformation were investigated. Exposure of cells to N'-nitrosonornicotine or 4-(N-methyl-N'-nitrosamino)-1-(3-pyridyl)-1-butanone followed by virus infection resulted in a significant enhancement of transformation frequency when compared with that observed with chemical carcinogens or virus alone. This study suggests that tobacco-specific N'-nitrosamines and Herpes simplex virus can interact together and show synergism in cell transformation.

... Young male and female mink (Mustela vision) were found to be highly susceptible to the carcinogenic effect of N-nitrosonornicotine (NNN). In this ... study /researchres/ tested (i) the importance of the age of the animals with regard to the carcinogenic effect of N'-nitrosonornicotine, (ii) the carcinogenic activity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and (iii) the combined carcinogenic effect of N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. (I) In a prior study, the latency of nasal tumor induction by N'-nitrosonornicotine (11.9 mM) averaged 84 +/- 40 weeks upon twice weekly applications, starting at the age of 3 weeks and continuing for 38 weeks. In this bioassay, giving N'-nitrosonornicotine in 28 weeks but starting at the age of 3 months, it took, on the average, 97 +/- 29 weeks to induce malignant nasal tumors, primarily esthesioneuroepithelioma with invasion of the brain. (ii) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (6.3 mM), given by sc injection, induced nasal carcinomas with invasion of the forebrain after 77 +/- 39 weeks. (iii) N'-nitrosonornicotine (11.9 mM) plus 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (6.3 mM) led to the same type of carcinoma but at an accelerated pace, namely after 71 +/- 57 weeks. This study supports the earlier observation that tobacco-specific N-nitrosamines induce malignant tumors of the nasal cavity with invasion of the brain, dependent to some degree on the age of the mink at first application. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone appears to be a stronger carcinogen than N'-nitrosonornicotine in mink which follows the observations made with mice, rats and hamsters. ... combined administration of N'-nitrosonornicotine with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induces a stronger carcinogenic effect than N'-nitrosonornicotine or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone given alone.

During incubation with hamster liver microsomes, the tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was metabolized by alpha-carbon hydroxylation, pyridine N-oxidation and carbonyl reduction. The modulation of the activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone to intermediates, alkylating microsomal proteins, by some compounds related to tobacco smoke, P-450 inhibitors, thiol and alcohol compounds, has been determined. Binding of both the pyridyloxobutyl and the methyl moieties of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone was inhibited by more than 40% by N'-nitrosonornicotine or N-nitrosodimethylamine. In contrast, nicotine and 3-acetylpyridine inhibited only the binding of the pyridyloxobutyl moiety. Binding of both moieties of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone was not inhibited by its deactivation metabolite, the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-Ne-oxide. Whereas the P-450 inhibitors metyrapone, (2-(diethylamino)ethyl 2,2-diphenyl pentenoate)hydrochloride and piperonyl butoxide inhibit the binding of the pyridyloxobutyl moiety selectively, carbon monoxide inhibits the binding of both moieties. Metyrapone reduced alpha-carbon hydroxylation but not pyridine N-oxidation, suggesting that in hamster livers pyridine N-oxidation is not mediated by P-450-dependent monooxygenases. The binding of the pyridyloxobutyl and methyl moieties was partially dependent on the presence of NADPH in the incubation mixture. Glutathione had no effect on the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone but inhibited the enzymatic and non-enzymatic binding of its pyridyloxobutyl moiety. ... the binding of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-derived intermediates to cellular proteins is inhibited by various substances present in tobacco smoke and by inhibitors of P-450 monooxygenases. Only part of this binding is enzymatically mediated.

TERRESTRIAL FATE: Based on a classification scheme(1), estimated Koc values of 1600 and 17(SRC), determined respectively from a structure estimation method(2) and using an estimated log Kow of 0.32(2) and a regression-derived equation(2), indicates that N-nitrosonornicotine may have very high to low mobility in soil(SRC). The contradiction may be explained by N-nitrosonornicotine's ability to protonate at environmental pHs(SRC). The estimated pKa of N-nitrosonornicotine is 5.25(3), indicating that this compound will partially exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Adsorption of pyridine has been observed to vary several orders of magnitude depending upon the pH of the soil matrix with sorption higher in acidic soil than in basic soil(5), and the pyridine ring is the structural portion of N-nitrosonornicotine that is protonated(SRC). Volatilization of N-nitrosonornicotine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.69X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(2). N-Nitrosonornicotine is not expected to volatilize from dry soil surfaces based on an estimated vapor pressure of 5.1X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). N-Nitrosonornicotine is expected to photolyze on surfaces exposed to sunlight(SRC) based on observed photolysis rates of similar nitrosamines in aqueous solution(6). Biodegradation data in soil were not available(SRC, 2012).

AQUATIC FATE: Based on a classification scheme(1), estimated Koc values of 1600 and 17(SRC), determined respectively from a structure estimation method(2) and using an estimated log Kow of 0.32(2) and a regression-derived equation(2), indicates that N-nitrosonornicotine may have no to strong adsorption to suspended solids and sediment(SRC). The estimated pKa of N-nitrosonornicotine is 5.25(3), indicating that this compound will partially exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(3); therefore, adsorption may be more likely to occur with the cation form under acid conditions(SRC). Volatilization from water surfaces is not expected(5) based upon an estimated Henry's Law constant of 1.69X10-10 atm-cu m/mole at 25 °C(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(6), an estimated BCF of 3(SRC), from an estimated log Kow of 0.32(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). The direct photolysis rate constant for the analogous compound N-nitrosopyrrolidine in aqueous solution exposed to irradiation representing Southern California midsummer, midday sun was observed to be 0.055/min with a half-life of 14 minutes and a quantum yield of 0.55(7); the photolysis rate N-nitrosonornicotine is expected to be similar(SRC). Biodegradation data in water were not available(SRC, 2012).

Burley tobacco was harvested at 1, 4, and 7 weeks after topping, ie, immature, mature, and overmature plants, respectively, and cured in two curing environments (24 °C at 70% relative humidity and 32 °C at 83% RH). Concentrations of N-nitrosonornicotine increased with time of curing and were markedly higher in the higher temperature, higher humidity treatment. N-nitrosonornicotine levels before curing were 0.40, 0.43, and 0.56 ug/g for the immature, recommended harvest time, and overmature tobacco. The maximum levels obtained during the 21 day curing period at the lower temperature and humidity, were 2.06 (day 21), 5.45 (day 19), and 4.74 (day 14) ug/g, respectively, for the three types of harvest. The maximum levels obtained during the 21 day curing period at the higher temperature and humidity were 88.33 (day 21), 221.96 (day 19), and 71.04 ug/g, respectively, for the three types of harvest.

Changes in N'-nitrosonornicotine (NNN) and its alkaloid precursors during growth and curing of tobacco were quantified in seven NC95 flue cured isolines with alkaloid levels ranging from 3 to 36 mg/g. Tobacco samples were taken at harvest (mature leaves), during flue curing at end of yellowing, and after curing was complete. Leaves were harvested at three primings (first= lower stalk position; second= middle stalk position; third= upper stalk position). Analysis was done by gas chromatography with a thermionic N-P detector. Mean NNN content (ug/g) increased during the curing process: 0.26 at harvest, 0.28 at end of yellowing, and 1.56 after curing. Leaves from higher stalk positions had higher levels of NNN (measured in ug/g): 0.19, 0.19, and 0.39 at harvest; 0.23, 0.17, and 0.44 at end of yellowing; and 0.88, 1.02, and 2.80 after curing. Nornicotine concentrations in the leaves were significantly correlated with NNN (0.95).

... Using 0.01N sodium hydroxide NNN /N'-nitrosonornicotine/ extracted from cigarette tobacco after 1, 2, 3, and 24 hr was 0.86, 0.84, 0.85, and 0.96 ug/g, respectively.

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

The Koc of N-nitrosonornicotine is estimated as 17(SRC), using an estimated log Kow of 0.32(1) and a regression-derived equation(1). Using a structure estimation method based on molecular connectivity indices(1), the Koc can be estimated to be 1600(SRC). According to a classification scheme(2), these estimated Koc values suggest that nornicotine may have very high to low mobility in soil. The contradiction may be explained by N-nitrosonornicotine's ability to protonate at environmental pHs(SRC). The estimated pKa of N-nitrosonornicotine is 5.25(3), indicating that this compound will partially exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Adsorption of pyridine has been observed to vary several orders of magnitude depending upon the pH of the soil matrix with sorption higher in acidic soil than in basic soil(5), and the pyridine ring is the structural portion of N-nitrosonornicotine that is protonated(SRC).

N-Nitrosopyrrolidine has been identified as a chemical component in tobacco(1). N-Nitrosonornicotine is reportedly produced by nitrosation of nicotine (the most prevalent alkaloid in commercial tobacco) during the curing, aging and processing of tobacco(2). N-Nitrosonornicotine may be formed in human saliva by the reaction of salivary nitrite with nicotine or nornicotine during oral use of snuff or chewing tobacco(2).

/HUMAN EXPOSURE STUDIES/ Smokers with head and neck squamous cell carcinoma (HNSCC) (cases) were compared with smokers without HNSCC (controls) in a matched cohort. The tobacco metabolites studied were: 1-hydroxypyrene (1-HOP), N'-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). In 33 subjects, mean 1-HOP was 1.82 pmol/mg creatinine versus 1.08 pmol/mg creatinine (p = .004) and mean NNN was 0.10 pmol/mg creatinine versus 0.04 pmol/mg creatinine (p = .01) in cases and controls, respectively. NNAL did not differ between groups. Smokers with HNSCC have elevated urinary levels of 1-HOP and total NNN compared with matched controls, suggesting an increased effective exposure to these carcinogens. ...

/HUMAN EXPOSURE STUDIES/ N-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are tobacco-specific nitrosamines. NNN and NNK can induce cancers of the esophagus and lung, respectively, in laboratory animals, but data on human esophageal cancer are lacking. The association between levels of NNN and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), an NNK metabolite, in urine samples collected before diagnosis and risk of esophageal cancer was examined in 77 patients with esophageal cancer and 223 individually matched controls, all current smokers, from a cohort of 18244 Chinese men in Shanghai, China, followed from 1986 to 2008. Urinary total NNN (free NNN plus NNN-N-glucuronide) was significantly higher, whereas the percentage of its detoxification product NNN-N-glucuronide was significantly lower in cases than controls. Odds ratios (95% confidence intervals) of esophageal cancer for the second and third tertiles of total NNN were 3.99 (1.25-12.7) and 17.0 (3.99-72.8), respectively, compared with the first tertile after adjustment for urinary total NNAL and total cotinine and smoking intensity and duration (P(trend) < 0.001). The corresponding figures for the percentage of NNN-N-glucuronides were 0.37 (0.17-0.80) and 0.27 (0.11-0.62) (P(trend) = 0.001). Urinary total NNN and the percentage of NNN-N-glucuronides almost completely accounted for the observed association for urinary total NNAL (free NNAL plus its glucuronides), urinary total cotinine and smoking intensity with esophageal cancer risk. ...

/SURVEILLANCE/ Reverse cigar smokers (who hold the burning end of cigars within the mouth), dippers (who place a mixture of Khaini tobacco and slaked lime into the lower gingival groove) and users of tobacco containing toothpaste (gudakhu) in Orissa, India, were examined for precancerous oral lesions, the frequency of micronucleated cells at 3 different intra-oral sites, and levels of tobacco specific nitrosamines (TSNA) in the saliva. Among reverse cigar smokers, a high incidence of leukokeratosis nicotina palati, an elevated frequency of micronucleated cells in the palate (2.5% as compared to 0.6% in non-smokers and non-chewers of tobacco) and tongue (2.1%) from which carcinomas preferentially develop, and up to 5890 ppb N-nitrosonornicotine and up to 1880 ppb N-nitrosoanatabine in the saliva were found. Among Khaini tobacco chewers, the frequency of micronucleated cells was elevated to 2.1% in the gingival groove, and up to 1580 ng N-nitrosonornicotine, 690 ng N-nitrosoanatabine, 90 ng N-nitrosoanabasine, and 180 ng 4-(methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone) per mL of saliva were observed. The localized elevation of the frequency of micronuclei and cancer development is probably due to a synergistic effect of hyperthermia and tobacco related carcinogens among reverse cigar smokers, and to the close, prolonged contact between the mucosa and tobacco among Khaini tobacco/slaked lime dippers. Neither precancerous lesions nor an elevated frequency of micronuclei were seen in the oral mucosa of users of gudakhu, a tobacco containing toothpaste, which may be due to the low amount of tobacco specific nitrosasmines released from the gudakhu and the short exposure time, which is restricted to the period of tooth brushing.

N-Nitrosonornicotine's limited production and use as a laboratory chemical(1) may result in its release to the environment through various waste streams(SRC). N-Nitrosonornicotine is formed by the combustion of tobacco(1); however, 40-50% of the N-nitrosonornicotine present in tobacco smoke has been shown to originate from direct transfer from N-nitrosonornicotine present in the unburned tobacco(1). The amount of N-nitrosonornicotine present in tobacco smoke appears to be correlated with the amount of nitrate in the tobacco(1,2); as the nitrate content increases, the N-nitrosonornicotine concn increases(1,2).

N'-Nitrosonornicotine (NNN) and 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK)

Group 1: Carcinogenic to humans

Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

2012

2009

NB Overall evaluation upgraded to Group 1 based on mechanistic and other relevant data

An estimated BCF of 3 was calculated for N-nitrosonornicotine in fish(SRC), using an estimated log Kow of 0.32(1) and a recommended regression-derived equation(1). According to a classification scheme(2), this BCF suggests that bioconcentration in aquatic organisms is low(SRC).

Toxic pollutant designated pursuant to section 307(a)(1) of the Federal Water Pollution Control Act and is subject to effluent limitations. /Nitrosoamines/

The levels for nitrosamines through ingestion of contaminated water and contaminated aquatic organisms ... which may result in incremental increase of cancer risk over the lifetime are estimated at 1X10-5, 1X10-6, and 1X10-7. The corresponding criteria are 8.0 ng/L, 0.8 ng/L, and 0.08 ng/L, respectively. For consumption of aquatic organisms only, excluding consumption of water, the levels are 12,400 ng/L, 1,240 ng/L, and 124 ng/L, respectively. /Nitrosamines/

Used as a research chemical; [HSDB]

The only known use of N.nitrosonornicotine is as a research chemical.

This is a toxic chemical found in cigarettes or generated by tobacco combustion.

(1977) NOT PRODUCED COMMERCIALLY IN USA

(1979) NOT PRODUCED COMMERCIALLY IN USA

REACTION OF NITROUS ACID WITH NORNICOTINE.

... /Prepared/ by treating nornicotine with sodium nitrite in dilute hydrochloric acid. ... It has also been made by the reaction of nicotine-N'-oxide with nitrites or nitrogen dioxide. ... No evidence was found that NNN has ever been produced in commercial quantities.