4-(N-나이트로소메틸아미노)-1-(3-피리딜)-1-뷰타논

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: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces 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: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No method should be applied ... until it has been thoroughly tested for its effectiveness & safety on material to be inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by reaction with 4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As a general technique ... treatment with sodium dichromate in strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 1-2 days is generally considered sufficient when freshly prepd reagent is used. ... Carcinogens that are easily oxidizable can be destroyed with milder oxidative agents, such as saturated soln of potassium permanganate in acetone, which appears to be a suitable agent for destruction of hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone (6 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens are used ... should be marked distinctively with appropriate labels. Access ... limited to persons involved in expt. ... A prominently displayed notice should give the name of the Scientific Investigator or other person who can advise in an emergency & who can inform others (such as firemen) on the handling of carcinogenic substances. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has occurred, such as spillage, should be decontaminated by lab personnel engaged in expt. Design of expt should ... avoid contamination of permanent equipment. ... Procedures should ensure that maintenance workers are not exposed to carcinogens. ... Particular care should be taken to avoid contamination of drains or ventilation ducts. In cleaning labs, procedures should be used which do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner equipped with high-efficiency particulate filter on exhaust, which are avail commercially, should be used. Sweeping, brushing & use of dry dusters or mops should be prohibited. Grossly contaminated cleaning materials should not be re-used ... If gowns or towels are contaminated, they should not be sent to laundry, but ... decontaminated or burnt, to avoid any hazard to laundry personnel. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in lab could build up during conduct of expt, periodic checks should be carried out on lab atmospheres, surfaces, such as walls, floors & benches, & ... interior of fume hoods & airducts. As well as regular monitoring, check must be carried out after cleaning-up of spillage. Sensitive methods are required when testing lab atmospheres. ... Methods ... should ... where possible, be simple & sensitive. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to skin, animals should be kept in cages with solid bottoms & sides & fitted with a filter top. When volatile carcinogens are given, filter tops should not be used. Cages which have been used to house animals that received carcinogens should be decontaminated. Cage-cleaning facilities should be installed in area in which carcinogens are being used, to avoid moving of ... contaminated /cages/. It is difficult to ensure that cages are decontaminated, & monitoring methods are necessary. Situations may exist in which the use of disposable cages should be recommended, depending on type & amt of carcinogen & efficiency with which it can be removed. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone (9 total), please visit the HSDB record page.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

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/

4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone is formed by oxidation and nitrosation of nicotine and is produced during the curing of tobacco and in smoking. 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone is extracted from snuff by the saliva of users, and as much as 0.2 g/g of saliva has been measured(1).

... Male ICR mice were exposed to NNK (0.5 mg/mouse) and sodium arsenite (0, 10, or 20 mg/kg) daily via gavaging for 10 days and their urine was collected at day 10 for NNK metabolite analysis. Liver samples were also obtained for CYP2A enzyme and DNA adducts evaluations. Both the cyp2a4/5 mRNA levels and the CYP2A enzyme activity were significantly elevated in arsenic-treated mice liver. Furthermore, urinary NNK metabolites in NNK/arsenic co-treated mice also increased compared to those treated with NNK alone. Concomitantly, DNA adducts (N(7)-methylguanine and O(6)-methylguanine) were significantly elevated in the livers of mice co-treated with NNK and arsenic. Our findings provide clear evidence that arsenic increased NNK metabolism by up-regulation of CYP2A expression and activity leading to an increased NNK metabolism and DNA adducts (N(7)-methylguanine and O(6)-methylguanine). These findings suggest that in the presence of arsenic, NNK could induce greater DNA adducts formation in hepatic tissues resulting in higher carcinogenic potential.

The NNK/mouse lung model has been used extensively by numerous investigators to determine factors, conditions, drugs or chemopreventive compounds that can modulate the formation of lung tumors in mice. One of these studies is summarized below. A study was conducted to determine the capacity of cigarette smoke to induce lung tumors and promote lung tumorigenesis induced by NNK. Groups of 20 female A/J mice, 7 weeks of age, were exposed for 6 hr per day on 5 days per week for 26 weeks to filtered air (FA), cigarette smoke (CS; diluted mainstream smoke (target concentration, 250 mg total particulate matter/cu m) from IR3 research cigarettes), NNK or NNK plus CS. Mice were exposed for 3 days to 50% of the target concentration of CS and for 4 days to 75% of the target concentration of CS before full exposure. Three days before CS exposure, mice received an intraperitoneal injection of 100 mg/kg bw NNK in 0.1 mL saline. Mice were killed 5 weeks after the exposures were terminated. Total tumors were enumerated macroscopically and characterized microscopically. Differences in survival were analysed by Breslow statistics in a Kaplan-Meier survival analysis. Student's t-test with a Bonferroni multiple comparisons correction was used to examine group differences in lung weight, tumor multiplicity for all animals and tumor multiplicity in tumor-bearing animals, with significance set at the p < 0.05 level. The lung tumor incidence among the four groups was: FA, 5/19 (26%); CS, 0/19 (0%); FA + NNK, 19/20 (95%); and CS + NNK, 13/16 (81%). The lung tumor multiplicities (total tumors/animal at risk) were: FA, 0.32 +/- 0.58 tumors per animal; FA+ NNK, 2.50 +/- 1.67 tumors per animal; and CS + NNK, 2.50 +/- 1.97. Those among tumour-bearing animals were: FA, 1.20 +/- 0.44 tumors per animal; FA+ NNK, 2.63 1.61 tumors per animal; and CS + NNK, 3.08 +/- 1.71. CS exposure decreased both body weights and lung weights, but treatment with NNK had no additional effect. Tumor multiplicity was greater in the FA + NNK- and the CS + NNK-treated groups compared with the FA- and CS-treated groups (p < 0.05) among all animals, but tumor multiplicity in the tumor-bearing animals did not differ between the FA-, FA + NNK- or CS + NNK-treated groups.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 320(SRC), determined from a structure estimation method(2), indicates that 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone is expected to have moderate mobility in soil(SRC). Volatilization of 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.3X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(3). 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.8X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2009).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 320(SRC), determined from a structure estimation method(2), indicates that 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 8.3X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3.2(SRC), from an estimated log Kow of 0(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2009).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone, which has an estimated vapor pressure of 6.8X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 22 hours(SRC), calculated from its rate constant of 1.8X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone may be removed from the air by wet or dry deposition(SRC). 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Exposure: Tobacco-specific N-nitrosamines, including 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK), N'-nitrosonornicotine (NNN), N'-nitrosoanabasine (NAB) and N'-nitrosoanatabine (NAT), occur widely in tobacco and tobacco smoke. They are formed by the nitrosation of nicotine and other tobacco alkaloids and have been detected in green tobacco leaves from Nicotiana tabacum and N. rustica species; however, the largest quantities of tobacco-specific N-nitrosamines are formed during tobacco curing and processing and additional amounts are formed during smoking. Tobacco-specific N-nitrosamines occur in all commercially and non-commercially prepared tobacco products including cigarettes, cigars, bidis, pipe tobacco and smokeless tobacco products. N-Nitrosamines occur in a wide variety of both food and non-food products, but the amounts of tobacco-specific N-nitrosamines in all tobacco products exceed the levels of other N-nitrosamines in other commercial products by several orders of magnitude. The highest levels of tobacco-specific N-nitrosamines are measured in smokeless tobacco products. ... The degree of exposure to tobacco-specific N-nitrosamines depends not only on the levels of these compounds in tobacco products or smoke, but also on the manner in which the products are used. Effects in Humans: No data were available. Effects in Animals: In numerous studies in mice, NNK induced lung adenomas independent of the route of administration. In studies by subcutaneous injection, benign and malignant tumors of the lung, nasal cavity and liver were induced in rats. In two of four experiments in hamsters, lung adenomas and adenocarcinomas or adenosquamous carcinomas were induced in males and females. In the two other experiments, adenomas were observed. Nasal cavity tumours involving the forebrain were observed in a limited study in mink. In a study by administration in the drinking-water and another by oral swabbing, combined benign and malignant lung tumours (adenoma, adenosquamous carcinoma and carcinoma) were induced in male rats. In the drinking-water study, NNK produced benign and malignant pancreatic tumours. In the oral swabbing study, combined benign and malignant tumours of the liver and nasal cavity were observed. Asignificant increase in the incidence of liver and lung tumours was reported in female rats when NNK was instilled into the urinary bladder. In two studies, the offspring of mice were exposed transplacentally by intraperitoneal injection of the dams. Liver tumors were observed in male offspring in both studies and in female offspring in one study. In one of these studies, lung tumors were also observed in male offspring. In studies of the offspring of hamsters given NNK during pregnancy, intratracheal instillation of the dams resulted in adenocarcinomas of the nasal cavity in male offspring and adrenal pheochromocytomas in male and female offspring in one study. In a second study, subcutaneous injection of NNK into dams induced respiratory tract (nasal cavity, larynx and trachea) tumors in male and female offspring. When dams were injected subcutanously or treated by intratracheal instillation, nasal cavity and adrenal gland tumors developed in male and female offspring in a third study. Intraperitoneal administration of NNK-N-oxide induced lung adenomas in female mice. In an oral swabbing study, NNK in combination with NNN increased the incidence of oral tumors in rats.

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/

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone can be estimated to be 320(SRC). According to a classification scheme(2), this estimated Koc value suggests that 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone is expected to have moderate mobility in soil.

/HUMAN EXPOSURE STUDIES/ 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen present in both unburned tobacco and cigarette smoke. The sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides, referred to as total NNAL, is an established urinary biomarker of human NNK uptake. Metabolic activation of NNK to DNA adducts proceeds via alpha-hydroxylation pathways, and 4-oxo-4-(3-pyridyl)butanoic acid (keto acid) and 4-hydroxy-4-(3-pyridyl)butanoic acid (hydroxy acid) are the principal end products of these pathways in rodents and primates. The purpose of this study was to determine NNK metabolic activation in smokers, as measured by the sum of keto acid and hydroxy acid, relative to total NNAL. To specifically identify NNK-derived keto acid and hydroxy acid, which are also formed from nicotine, we added [pyridine-D(4)]NNK to cigarettes that were originally low in NNK, and measured the deuterium-labeled metabolites in the urine of people who smoked these cigarettes. The total amount of [pyridine-D(4)]keto acid plus [pyridine-D(4)]hydroxy acid averaged 4.00 +/- 2.49 nmol/24 hr, whereas the average amount of total [pyridine-D(4)]NNAL was 0.511 +/- 0.368 nmol/24 hr. The results of this study show for the first time that NNK metabolic activation is a quantitatively significant pathway in smokers, accounting for approximately 86% of total urinary excretion of NNK metabolites. The large interindividual variation in the excreted [pyridine-D(4)]keto acid and [pyridine-D(4)]hydroxy acid among 20 smokers strongly supports our hypothesis that some smokers activate NNK more extensively than others and that the ratio between biomarkers of metabolic activation and detoxification at a given dose of NNK could be a potential indicator of cancer risk.

/EPIDEMIOLOGY STUDIES/ 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (sum of which is denoted as total NNAL) are metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK and NNAL can induce lung cancer in laboratory animals but human data are limited. The association between prediagnostic levels of urinary total NNAL and risk of lung cancer development was evaluated in two prospective cohorts of Chinese cigarette smokers. ... A nested case-control study /was conducted/ involving 246 cases of incident lung cancer and 245 cohort controls who were individually matched to the index cases by age, gender, neighborhood of residence at cohort enrollment, and date of urine collection. Urinary levels of total NNAL were significantly associated with risk of lung cancer in a dose-dependent manner. Relative to the lowest tertile, risks associated with the second and third tertiles of total NNAL were 1.43 [95% confidence interval (95% CI), 0.86-2.37] and 2.11 (95% CI, 1.25-3.54), respectively (P for trend=0.005) after adjustment for self-reported smoking history and urinary total cotinine. Smokers in the highest tertiles of urinary total NNAL and total cotinine exhibited a 8.5-fold (95% CI, 3.7-19.5) increased risk for lung cancer relative to smokers with comparable smoking history but possessing the lowest tertiles of urinary total NNAL and total cotinine. Findings of the present study directly link NNK exposure to lung cancer development in humans.

4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone's formation during curing of tobacco leaves, and subsequent presence in cigarette smoke and snuff(1), formation during various manufacturing processes(2), and limited application as a laboratory reagent(3) may result in its release into the environment through various waste streams(SRC).

An estimated BCF of 3.2 was calculated in fish for 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone(SRC), using an estimated log Kow of 0.0(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone is estimated as 8.3X10-14 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone is expected to be essentially nonvolatile from water surfaces(2). 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone's Henry's Law constant indicates that volatilization from moist soil surfaces will not occur(SRC). 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.7X10-5 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of 25 female strain A/J mice, 6 to 8 weeks of age, received thrice-weekly intraperitoneal injections of 0.1 mL of a 1% solution of NNK [purity not specified] in trioctanoin for a total of 22 injections (total dose, 22 mg or 0.11 mmol per mouse) and were observed for 30 weeks after the final injection. Controls consisted of groups of 25 of untreated mice, vehicle controls and positive (urethane-treated) controls. When animals were killed, lungs were examined macroscopically for total lesions and microscopically for histological type. The Student's t-test was used to determine statistical significance. In untreated controls, 1/25 animals developed lung tumors at a multiplicity of 0.04 +/- 0.20 tumors per mouse; in the vehicle controls, 5/24 animals developed lung tumours at a multiplicity of 0.2 +/- 0.41 tumours per mouse. Of the NNK-treated animals, 20/23 developed lung tumors with a multiplicity of 2.61 +/- 1.85 tumours per mouse (p < 0.05 compared with vehicle controls). Tumors were described as adenomas.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of 25 female strain A/J mice, 6-8 weeks of age, received thrice-weekly intraperitoneal injections of 0.1 mL of a 1% solution of NNK (> 99% pure) suspended in trioctanoin for 7.3 weeks (22 injections; total dose, 0.11 mmol/mouse) and were held for 30 weeks after the last injections. Untreated and vehicle-treated animals served as controls. formalin for histological evaluation. The Student's t-test was used to determine statistical significance. Of the NNK-treated mice, 23/23 developed 865 lung tumours (412 carcinomas) with a multiplicity of 37.6+/- 11.8 tumors per mouse (p < 0.0001 compared with vehicle controls). Six treated mice had tumors other than lung adenomas: three hepatocellular adenomas, two hepatocellular carcinomas and one squamous-cell papilloma of the nasal cavity. In untreated animals, 10/25 animals developed lung adenomas with a multiplicity of 0.6 +/- 0.9 adenomas per surviving mouse whereas 4/25 trioctanoin controls developed lung adenomas with a multiplicity of 0.2 +/- 0.5 adenomas per mouse.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In a study in which NNK and several structural analogues of NNK and NNN were examined, groups of 30 female strain A/J mice, 6 to 8 weeks of age, received thrice-weekly intraperitoneal injections of NNK (total dose, 20 umol/mouse) in 0.2 mL saline for 7 weeks. NNK was synthesized and considered pure by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Mice were held for 30 weeks after the last injection. The Student's t-test was used to determine statistical significance. Saline control mice had a lung tumor incidence of 40% (12/30), with a tumor multiplicity of 0.5 +/- 0.7. NNK induced a 100% (30/30) incidence of lung tumors with a multiplicity of 7.2 +/- 3.4 tumors per mouse (p < 0.0001).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of 25 female strain A/J mice mice [age unspecified] received thrice-weekly intraperitoneal injections of NNK (99% pure by HPLC and gas chromatography-mass spectrometry) in 0.1 mL saline for a total of 20 injections (total dose, 20 umol/mouse). Animals were held for 30 weeks after the final injection and statistical significance wasevaluated using Student's t-test. Controls consisted of animals injected over the same schedule with saline only. NNK induced a lung tumor incidence of 100% (25/25) and a multiplicity of 15.7 +/- 4.1 tumours per mouse (saline control: 20% incidence (5/25); tumor multiplicity of 0.20 +/- 0.40 tumours per mouse; [p < 0.0001]). Twenty-three treated mice had adenomas only and two had both adenomas and adenocarcinomas.

A constituent of tobacco smoke; [ChemIDplus]

NNK has no known use other than as a laboratory chemical.

... By reaction of sodium hydroxide and sodium nitrite with 4-(N-methyl)-1-(3-pyridyl)-1-butanone dichloride

One of the products of the reaction of nicotine with nitrite