N-Nitrosopyrrolidine

100.12

100.12

213-218-8

SZ4J5WK201

18797

2810|3082

DTXSID8021062

C44424

Yellow liquid

2933990090

32.7

-0.19

N-nitrosopyrrolidine is a yellow liquid found in certain food products and tobacco smoke. Probably a carcinogen.

1.10 g/cm³

214 °C @ Press: 760 Torr

182 °F

1.565

soluble in org solvents and lipids

Refrigerator

0.06 mm Hg at 20 deg C

LD50 orally in rats: 900 mg/kg (Druckrey)

Henry's Law constant = 4.89X10-8 atm-cu m/mol at 37 °C

Can be steam-distilled; strong oxidants (peracids) oxidize it to corresponding nitramine; can be reduced to corresponding hydrazine and/or amine; relatively resistant to hydrolysis, but can be split by hydrogen bromide in acetic acid|Hydroxyl radical reaction rate constant = 1.55X10-11 cu cm/molecule-sec at 25 °C (est)

Soluble in water.

Azo, Diazo, Azido, Hydrazine, and Azide Compounds

A cyclic nitrosamine. Nitrated organics, such as N-NITROSOPYRROLIDINE, range from slight to strong oxidizing agents. If mixed with reducing agents, including hydrides, sulfides and nitrides, they may begin a vigorous reaction.

III

6.1(b)

2810

3

40

UY1575000

Xn

Half-lives of N-nitrosos compounds at 110 deg C in phosphate buffers: N-nitrosopyrrolidine pH 2.2/150 days; pH 4.0/55 days; pH 5.5/28 days; pH 7.0/28 days; pH 8.5/11.4 days; pH11.0/1.1 days; pH12.2/1.0 day. /from table/

P281

H302-H351

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U180, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.|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.|A potential candidate for liquid injection incineration at a temperature range of 650 to 1,600 °C and a residence time of 0.1 to 2 seconds. A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.|A one-step procedure for chemically degrading nitrosamine residues generated in research laboratory is described. Treatment with aluminum-nickel alloy powder & aqueous alkali rapidly reduced all 11 nitrosamines studied to the corresponding amines. Hydrazines were produced as transitory intermediates, but these potential carcinogens were also reduced under the conditions employed, & no products except amines, ammonia, & in some cases, alcohols were detected in the final reaction mixtures. Various solvent systems are discussed. Some of the nitrosamines degraded were NDMA, N-nitrosodiethylamine, N-nitrosodiisopropylamine, NDBA, N-nitrosomorpholine, N-nitroso-N-methylaniline, N-nitrosomethyl(methoxymethyl)amine, & N-nitroso-N,O-dimethylhydroxylamine. /Nitrosamines/|For more Disposal Methods (Complete) data for N-NITROSOPYRROLIDINE (14 total), please visit the HSDB record page.

Oxidizers.

U.S. Department of Health & Human Services/National Toxicology Program; Twelfth Report on Carcinogens (2011). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. N-Nitrosopyrrolidine (930-55-2) was first listed in the Second Annual Report on Carcinogens (1981) as reasonably anticipated to be a human carcinogen.[Available from, as of August 3, 2012: http://ntp.niehs.nih.gov/]|Cottrell RC et al; Investigations of the bioactivation of N-nitrosopyrrolidine in the rat; Adv Exp Med Biol 136B (Biol React Intermed-2, Chem Mech Biol Eff, part B): 1165-71 (1982). A review of metabolism incl 3 routes of biodegradation & speclations on their relative significance in bioactivation & detoxification.|TSCA CHIPs present a preliminary assessment of N-nitrosopyrrolidine's potential for injury to human health & the environment (available at EPA's TSCA Assistance Office: (202) 554-1404|USEPA; Ambient Water Quality Criteria Doc: Nitrosamines (1980) EPA-440/5-80-064.|For more Special Reports (Complete) data for N-NITROSOPYRROLIDINE (6 total), please visit the HSDB record page.

Combustible. (NTP, 1992)|Carcinogens, Flammable - 2nd degree

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P264, P270, P281, P301+P312, P308+P313, P330, P405, and P501|Aggregated GHS information provided by 47 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: You should dampen the solid spill material with acetone, then transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the adsorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store it in a freezer. (NTP, 1992)

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. 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). RECOMMENDED GLOVE MATERIALS: Permeation data indicate that neoprene gloves may provide protection to contact with this compound. Neoprene over latex gloves is recommended. However, if this chemical makes direct contact with your gloves, or if a tear, puncture or hole develops, remove them at once. (NTP, 1992)|PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent ... Safety pipettes ... for all pipetting. ... In animal laboratory ... 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 ... when working with particulates or gases, & disposable plastic aprons ... gowns ... /should be/ of distinctive color. /Chemical carcinogens/|Wear nitrile rubber gloves, protective laboratory coat, self-contained breathing apparatus, eye protection and protective shoes. /Nitrosamines/

Use dry chemical, carbon dioxide, alcohol foam, or polymer foam extinguishers.

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/|Decontamination of N-nitrosamine contaminated glassware /was described/. /N-Nitrosamines/|Nitrosamine residues generated in laboratory research or accidental spills in research laboratories and diluted to concn of 10 mg/L or less are rapidly reduced to innocuous amines, ammonia, or alcohols by aluminum-nickel alloy powder and aqueous alkali. The method is applicable to a variety of media (water, mineral oil, olive oil, dimethylsulfoxide, soln of agar gel) but is not recommended for use with nitrosamines in acetone or dichloromethane because reactions are slow and incomplete. After the reduced reaction mixture is filtered, the liquid is disposed of by pouring it over sufficient absorbent material to convert it to a solid waste for incineration. /Nitrosamines/

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|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 additional protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/|For more Preventive Measures (Complete) data for N-NITROSOPYRROLIDINE (11 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

Contact can irritate the skin and eyes.

U180; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 1 lb or 0.454 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

U180; As stipulated in 40 CFR 261.33, when N-nitrosopyrrolidine, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

N-Nitrosopyrrolidine was found at concentrations of 0.09-0.02 ug/L in water from 2 to 19 chemical factories(1). N-Nitrosopyrrolidine concentrations of 4.2 ppb and 1.3 ppb were found in municipal sewage sludge from San Diego and Seattle, respectively(2). Analysis of anaerobic digester mixed liquor (ADML) from three wastewater treatment plants in the southeastern US detected N-nitrosopyrrolidine concentrations of <25 ng/L(3); N-nitrosopyrrolidine concentrations in the primary sludge supernatant and thickened waste-activated sludge ranged from <50 to 59 ng/L(3).

N-Nitrosopyrrolidine (NPYR) concentrations ranged from not detected to 3.9 ug/cm m in a rubber plant that was producing bias ply tires (feed mill and calender location)(1). Average NPYR concentration for area, process, and personal samples was 0.26 ug/cu m in the air of 8 rubber producing facilities (total of 45 samples)(1).

N-Nitrosopyrrolidine has been identified as a chemical component in tobacco(1). N-Nitrosopyrrolidine has been reported at 7 to 113 ng/cigarette, at 5.1 to 34 ng/cigarette (5 kinds of cigarettes), and from 115 to 1600 ug/kg in the scrapings of pipes used for smoking tobacco(2). N-Nitrosopyrrolidine has also been found in the vapor over frying bacon(2). The mean emission factor for N-nitrosopyrrolidine in environmental tobacco smoke for six commercial cigarette brands was 104 ng/cigarette with a standard deviation of 20 ng/cigarette(3). The occurrence of N-nitrosopyrrolidine in 10 German filter and non-filter cigarettes was 0.6 to 2.9 and 1.8 to 5.2 ng/cigarette, respectively(4). The occurrence of N-nitrosopyrrolidine in mainstream smoke from 10 German filter and non-filter cigarettes was 3.9 to 15.2 and 6.9 to 41.2 ng/cigarette, respectively(4). The concentration of N-nitrosopyrrolidine in smoke condensate extracts from 11 tobacco types or blends ranged from 1 to 110 ng/cigarette with a median of 26 ng/cigarette(5). Another investigator reports the amount of N-nitrosopyrrolidine in mainstream cigarette smoke as (product, ug/cigarette): commercial U.S. cigarettes, 5 to 33; French cigarettes, 11 to 25; low-nitrate experimental cigarettes, 3 to 6; high-nitrate experimental cigarettes, 32 to 52; small cigars, 5(6). For sidestream smoke the amount of N-nitrosopyrrolidine is (product, ug/cigarette): commercial U.S. cigarettes, 205 to 390; small cigars, 612(6). The concentration of N-nitrosopyrrolidine in the mainstream smoke of 20 commercial brands of filter and non-filter cigarettes was 3.9-41.2 ng/cigarette; concentration in the cigarette tobacco was much less(7).|N-Nitrosopyrrolidine was present in rubber nipples for baby bottles from Brazil; its concentration in these products was not reported(1). N-Nitrosopyrrolidine was detected in combustion smokes from the following samples(1): black pepper, 750 ng/g; soy sauce, 64 ng/g; semi-dried fish, 333 ng/g; dried squid, 2040 ng/g; pork vienna, 37 ng/g; chicken, 54 ng/g; beef, 72 ng/g; cigarette (mainstream), 270 ng/g; cigarette (sidestream), 996 ng/g; mosquito repellent, 17 ng/g; hair, 940 ng/g(2).|Nitrosamines such as... nitrosopyrrolidine are detected in elastomeric products such as rubber nipples or plugs for injectables. The total nitrosamine content in rubber nipples varies from 45-93 mumol/kg.

... Oral administration of ethanol (6.3 g/kg bw) 1 hr prior to administration of ... N-nitrosopyrrolidine resulted in a substantial reduction of genotoxicity that was more pronounced in the liver as compared to lungs, spleen, kidneys and blood. However, when the same ethanol dose was given 26 hr before ... N-nitrosopyrrolidine, an increase of DNA damage was found, that was, in most cases, higher in the kidneys than in the liver. Significant enhancement of genotoxic activity was also measured in lungs and spleen, whereas only a marginal increase was detectable in the blood. Repeated administration of smaller ethanol doses (2.0 g/kg body wt at 12 hr intervals) for 4 days caused a comparable increase. Similar enhancement of genotoxicity was also measured when acetone (3.5 g/kg) was given orally 15 hr before nitrosamine administration. The stimulating effect of ethanol was dose dependent and was absent when the alcohol was administered 60 hr prior to the nitrosamine. ...|N-nitrosopyrrolidine (NPYR) is an important carcinogen, frequently present in the environment and food chain. Oral administration of NPYR to experimental rats evoked severe biochemical and pathological changes. In the present investigation, the protective role of dietary fibre on NPYR-induced toxicity in hypercholesterolemic rats was studied. Supplementation of chickpea seed coat fibre in the diet reduced the hepato-toxic effects of NPYR, as evident from the decreased hepatic degeneration and improved liver weight index compared to control. Administration of NPYR resulted in an increase in the osmotic fragility of erythrocytes in the experimental animals. The antioxidant potential of experimental animals decreased in the NPYR-fed group, which was evident from the increased in vitro lipid peroxidation (LPO) of erythrocytes. However, chickpea seed coat fibre considerably reduced the peroxidative damage done by NPYR. Administration of NPYR resulted in a substantial and significant increase in LPO in all tissues, to a varying degree, though the effect was maximum in the case of the liver. Inclusion of chickpea seed coat fibre considerably reduced the peroxidative damage caused by NPYR in all tissues. The effect of NPYR administration on antioxidant potential was variable in different tissues, but the effect was reduced considerably on inclusion of chickpea seed coat fibre in the diet, providing reasonable protection against NPYR-induced oxidative stress, and, hence, its toxicity. Histopathological analysis of different tissues (heart, liver, lungs, spleen and kidneys) showed mild to severe pathological changes among the control and experimental groups. However, the pathological effects of NPYR administration were markedly reduced with the addition of chickpea seed coat fibre in the diet.|Inclusion of 10% ethanol with 6.8 ppm N-nitrosodiethylamine in the drinking water of strain A male mice resulted in a 4-fold enhancement of multiplicity of lung tumors and a 16-fold increase in incidence of forestomach tumors, compared with carcinogen alone. Given with 40 ppm N-nitrosopyrrolidine, ethanol caused a 5.5-fold increase in lung tumor multiplicity. ... The data provide additional support for the proposal that co-administered ethanol increases the tumorigenicity of nitrosamines by blocking hepatic first-pass clearance.|The effect of chronic ethanol consumption by hamsters on the carcinogenicity & target tissue metabolism of N-nitrosopyrrolidine (NPYR) was examined. Ethanol-consuming hamsters treated with NPYR developed more nasal cavity & tracheal tumors than controls. Tracheal rings isolated from ethanol-consuming hamsters metabolized NPYR at a higher rate than similar preparation from control animals.|For more Interactions (Complete) data for N-NITROSOPYRROLIDINE (14 total), please visit the HSDB record page.

Oral LD50 rat = 900 mg/kg|LD50 Mouse subcutaneous 125 mg/kg|LD50 Mouse oral 125 mg/kg|LD50 Hamster oral 1023 mg/kg

The most significant source of N-nitrosamines and N-nitrosamides in the environment is probably nitrosation of amine and amide precursors. These reactions may occur in air, soil, water, food and animal systems, when the precursors are present simultaneously. /N-Nitrosamines and N-Nitrosamides/

N-Nitrosopyrrolidine occurs in processed meats, cigarette smoke, and spice premixes.|No information was found that indicated N-nitrosopyrrolidine is produced commercially(1). N-Nitrosopyrrolidine may be released to the environment from cigarette smoke (mainstream and sidestream), frying of bacon, wastewater discharges, and sewage sludge(1). N-Nitrosopyrrolidine has also been detected in air samples at a rubber tire plant(2). Most of the N-nitrosopyrrolidine found in tobacco smoke is formed during the pyrolysis of the tobacco(3). Tobacco grown in high nitrogen soil had considerably more N-nitrosopyrrolidine than that grown in low nitrogen soil(4).

TERRESTRIAL FATE: Based on a classification scheme(1), estimated Koc values of 92 and 6(SRC), determined respectively from a structure estimation method(2) and using a log Kow of -0.19(3) and a regression-derived equation(2), indicates that N-nitrosopyrrolidine may have very high to high mobility in soil(SRC). Volatilization of N-nitrosopyrrolidine from moist soil surfaces is not expected to be an important fate process(SRC) given a measured Henry's Law constant of 4.89X10-8 atm-cu m/mole at 37 °C(4). N-Nitrosopyrrolidine is not expected to volatilize from dry soil surfaces based on a measured vapor pressure of 0.06 mm Hg at 20 °C(5). N-Nitrosopyrrolidine absorbs UV light strongly above 290 nm with a log epilson maxima of 2.2 at 335 nm(6) and a quantum yield of 0.55 in aqueous solution exposed to simulated sunlight(7); therefore, N-nitrosopyrrolidine is expected to be susceptible to direct photolysis on soil surfaces exposed to sunlight(SRC).|AQUATIC FATE: Based on a classification scheme(1), estimated Koc values of 92 and 6(SRC), determined respectively from a structure estimation method(2) and using a log Kow of -0.19(3) and a regression-derived equation(2), indicates that N-nitrosopyrrolidine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon a Henry's Law constant of 4.89X10-8 atm-cu m/mole atm-cu m/mole(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow of -0.19(3), suggests that bioconcentration in aquatic organisms is low(SRC). The direct photolysis rate constant for 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). N-Nitrosopyrrolidine is stable at room temperature for more than 14 days in neutral or alkaline aqueous solutions in the dark(8).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), N-nitrosopyrrolidine which has a measured vapor pressure of 0.06 mg Hg at 20 °C(2) will exist solely as a vapor in the ambient atmosphere. Vapor-phase N-nitrosopyrrolidine 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 25 hours(SRC), calculated from its rate constant of 1.55X10-11 cu cm/molecule-sec at 25 °C that was derived using a structure estimation method(3). N-Nitrosopyrrolidine absorbs UV light strongly above 290 nm with a log epilson maximum of 2.2 at 335 nm(4) and a quantum yield of 0.55 in aqueous solution exposed to simulated sunlight(5); therefore, N-nitrosopyrrolidine is expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of N-nitrosopyrrolidine with photochemically-produced hydroxyl radicals has been estimated as 1.55X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 25 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The direct photolysis rate constant for 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(2); the quantum yield was 0.55(2). N-Nitrosopyrrolidine is stable at room temperature for more than 14 days in neutral or alkaline aqueous solutions in the dark(3). It is slightly less stable in acidic solutions(4). At intermediate pH values (pH 4-7) and 110 °C, N-nitrosopyrrolidine and another compound (dimethylnitrosamine) had half-lives ranging from 16 to 55 days (half-life for each specific compound was not specified)(4). N-Nitrosopyrrolidine absorbs UV light strongly above 290 nm with a log epilson maximum of 2.2 at 335 nm(5); therefore, N-nitrosopyrrolidine is expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for N-nitrosopyrrolidine(SRC), using a log Kow of -0.19(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 Koc of N-nitrosopyrrolidine is estimated as 6(SRC), using a log Kow of -0.19(1) and a regression-derived equation(2). Using a structure estimation method based on molecular connectivity indices(2), the Koc of can be estimated to be 92(SRC). According to a classification scheme(3), these estimated Koc value suggest that N-nitrosopyrrolidine may have very high to high mobility in soil.

The Henry's Law constant for N-nitrosopyrrolidine is 4.89X10-8 atm-c m/mol at 37 °C(1). This value indicates that N-nitrosopyrrolidine will be essentially nonvolatile from water surfaces(2). N-Nitrosopyrrolidine's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to be an important fate process(SRC). N-Nitrosopyrrolidine is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.06 mm Hg at 20 °C(3).

DRINKING WATER: N-Nitrosopyrrolidine concentrations of 18-70.5 ng/L (detection limit of 2.1 ng/L) were detected in water from four distribution systems in Canada(1).

IIn the US, the average content in bacon is decreasing. A study in 1971-1974 showed 67 ug/kg; in 1975-76, the value was 17 ug/kg.|NPYR /N-nitrosopyrrolidine/ was found in 50% of 46 samples of several types of animal feed at levels of 1-26 ug/kg. ... Found levels of 2-8 ug/kg in 5/6 fishmeal samples.|N-Nitrosopyrrolidine has been found in a number of foods, primarily meat products(1).[Table#5171]|Dry premixed cures containing spices and sodium nitrite were found to contain up to 40 ug/kg NPYR /N-nitrosopyrrolidine/ when received; this could increase up to 520 ug/kg during 6-mo storage. ... Found 730 ug/kg NPYR in a spice-cure mixture buffered with sodium carbonate.|None of the 11 types of cheese (9 Italian, 2 Dutch) analyzed for volatile nitrosamines contained N-nitrosopyrrolidine (detection limit 1.67 ug/kg)(3). The concentration of N-nitrosopyrrolidine in 15 samples of smoked fried bacon and 10 samples of unsmoked fried bacon was <2.0 to 19.0 ug/kg and <2.0 to 9.0 ug/kg, respectively; the median concentrations were 9.0 and 4.0 ug/kg, respectively(1). Of 25 samples of cheese, meat and fish analyzed for N-nitrosopyrrolidine, levels were <0.5 ug/kg in 8 samples and ranged from 1.0 to 11.0 ug/kg in the other samples(2). The food containing 11 ug/kg was fried pig's liver. Samples of fried dry-cured bacon and drippings from 16 production plants contained mean N-nitrosopyrrolidine concentrations of 3.4 to 15.9 and 7.6 to 42.1 ppb, respectively(4). In a preliminary survey of the Italian market, the concentration of N-nitrosopyrrolidine in canned pork with jelly was 2.35 ppb; its concentrations in other luncheon meat products ranged from <0.3 to 5.88 ppb and it was not detected in cured meat products (detection limit 0.3 ppb)(5). Only two of 63 samples of various fish and seafoods analyzed for volatile nitrosamines contained N-nitrosopyrrolidine, smoked cod and smoked kippers, containing 1.9 ppb each (detection limit 0.1 to 0.2 ppb)(6). N-Nitrosopyrrolidine was detected 75 samples of fried pork bacon at a range of 0.7-25 ug/kg (mean 6.7 ug/kg)(7).

... Reported the presence of 1-110 ng/cigarette NPYR /N-nitrosopyrrolidine/ in tobacco smoke condensate; /other/ levels of 7-113 ng/cigarette. From 5.1-34 ng/cigarette were found in 5 kinds of cigarettes. Levels of 115-1600 ug/kg have been found in the scrapings of pipes used for smoking tobacco. ...|The most probable route of human exposure to N-nitrosopyrrolidine by the general population is through inhalation of tobacco smoke and vapor from frying bacon and other cured meats and the ingestion of certain foods, especially cured meats and fish(3,4). Occupational exposure via inhalation and dermal contact may occur in industries such as rubber manufacturering(1). Using average emission factors for N-nitrosopyrrolidine from cigarettes, the estimated average concn of N-nitrosopyrrolidine in a typical residence (volume 352 cu m, air exchange rate 0.58 1/hr and 16 cigarettes smoked per day) over a 40-hr week was 0.4 ng/cu m(2). In a typical office scenario (volume 1059 cu m, 16 occupants, 20% smokers each smoking 2 cigarettes per hour, air exchange 0.51 1/hr for daytime working hours and 0.41 1/hr for the remainder of the day), the estimated average concn of N-nitrosopyrrolidine was 1.0 ng/cu m(2).|During an inital survey of a tire manufacturing plant in Maryland, N-nitrosopyrrolidine was found in air samples with maximum and avg levels of 3.4 ug/cu m and 2.3 ug/cu m being found in the hot process area(1). However, over the next seven months, improvements in ventilation and changes in chemical formulation of the rubber reduced the concentration to undetectable levels(1). A NIOSH survey of a rubber vehicle sealing plant in May 1994 resulted in N-nitrosopyrrolidine concentrations in personal breathing zone samples of salt bath line operators, salt bath line feeders and assistants and molding/finishing operators of 0.04-0.08, <0.01-0.12, and 0.01-0.06 ug/cu m(2). General air samples contained 0.05-0.16 ug/cu m of N-nitrosopyrrolidine(2). On-site surveys of nitrosamines in the factory environment conducted between July 1977 and July 1981 of 7 industries found concentrations of N-nitrosopyrrolidine (n=45) in air sampling of 7 rubber plants of 0.02-3.9 ug/cu m with a mean of 0.26 ug/cu m(3).|Surveys conducted at 55 sites in 40 facilities involved in the manufacture, processing or use of azo dyes, fish meal, cutting fluids, rubber, detergents and surfactants (including tanning facilities and foundries) revealed airborne concentrations of compounds responsive to the Thermal Energy Analyser (TEA) in 25 plants. The dye industry had unidentified TEA-responsive materials at levels as high as 40 ug/cu m. ... N-nitrosodiphenylamine, N-nitrosopyrolidine and N-nitrosodimethylamine were detected in the work environment of tire plants. Engineering controls and chemical substitution were used to improve the environment in tire plants. Exposed workers were surveyed by sampling blood, urine and feces.

After ip administration of 6 mg/kg bw (2,5-(14)c)- or (3,4-(14)c)-NPYR to rats, these compounds were converted to (14)CO2 to extent of 18-25% within 6 hr; 7% of radioactivity was excreted in urine and only 1-2% in feces. Oral dose of 4 mg/kg bw (2,5-(14)c)-NPYR was converted to (14)CO2 to extent of 77%, while only 14% of dose of 650 mg/kg bw appeared as (14)CO2 in 24 hr.|Whole-body autoradiography performed with hemisections of mice at -80 °C and dry tape-sections, using pretreated and non-pretreated mice, indicated uniform distribution of non-metabolized N-nitrosopyrrolidine in tissues. At the shortest survival intervals (1 and 5 min) a high level of metabolites were found in liver, tracheo-bronchial and nasal mucosa and harder's gland which indicates local formation of metabolites in these tissues. At later survival intervals (0.5-24 hr) metabolites were in addition found in tissues with rapid cell turnover and high rate of protein synthesis and in brown fat.|... Nitrosamines ... can presumably cross the placenta since they are capable of inducing neoplasma in the offspring if administered to rats in late pregnancy. /Nitrosamines/|Differential pulsed polarography in 0.05M sulfuric acid was used for the determination of urinary concentration of nonmetabolized N-nitrosamines in rats 24-72 hr after intragastric administration of 0.01-0.5 LD50 of ... N-nitrosopyrrolidine. ... Most of the nitrosamines were recovered in urine in less than or equal to 10% of the administered amounts. ...

An excellent correlation was found between the metabolism of nitrosopyrrolidine and nitrosohexamethylenimine (probably via oxidation at the alpha-C) in rat liver microsomes and mutagenic potency in 2 bacterial mutagenic systems.|The structures of the DNA adducts formed in the metabolism of cyclic (carcinogen) N-nitrosamines are not known. The reactions with deoxyguanosine, catalyzed by porcine liver esterase, of alpha-acetoxy-N-nitrosopyrrolidine and 4-(carbethoxynitrosamino) butanal which are stable precursors to the reactive intermediates, alpha- hydroxy-N-nitrosopyrrolidine and 3-formyl-1-propanediazohydroxide, formed in the alpha-hydroxylation of the cyclic nitrosamine, N-nitrosopyrrolidine were studied. The same 2 major deoxyguanosine adducts were produced in each reaction. They were isolated by high-performance liquid chromatography and characterized by their UV spectra, mass spectra and proton magnetic resonance spectra. On the basis of these spectral data, the structures of the 2 major adducts were assigned as 3-(2-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8R- hydroxy-6R-methylpyrimido (1,2-a)purine-10(3H)one and 3-(2-deoxy-beta-D-erythro- pentofuranosyl)-5,6,7,8-tetrahydro-8S-h-ydroxy-6S-methylpyrimido(1,2,-a)purine- 10(3H)one, in which a new saturated 6-membered ring is formed by reaction at the 1- and N2-positions of deoxyguanosine. The same 2 adducts were formed in the reaction of crotonaldehyde (2-butenal) with deoxyguanosine. Mild acid hydrolysis of each of the 2 diastereomeric deoxyguanosine adducts yielded a pair of enantiomeric tricyclic 1,N2-guanine derivatives which had spectral properties in accordance with the assigned structures. Treatment of these tricyclic 1,N-2-guanine derivatives with sodium hydroxide and sodium borohydrate yielded N2-(3-hydroxy-1- methylpropyl) guanine, confirming the structural assignments. Unlike saturated dialkylnitrosamines which are metabolized to intermediates that give mainly 7-alkylation of deoxyguanosine, the intermediates formed in the alpha-hydroxylation of a cyclic nitrosamine, N-nitrosopyrrolidine, modify deoxyguanosine by forming cyclic 1,N2-adducts.|It is interesting to note that apparently all N,N-dialkylnitrosamines containing a tert-butyl group are noncarcinogenic. The list includes N-nitroso-1-proline, found in cured meats, particularly bacon. Although noncarcinogenic itself, nitrosoproline gives rise to the carcinogenic N-nitrosopyrrolidine during cooking. Aromatic nitrosamines are capable of transnitrosation, ie, under suitable conditions, their nitroso group can be transferred to appropriate amine-type compounds. It is thus possible that noncarcinogenic transnitrosating agents could form new carcinogenic N-nitroso compounds in the stomach.|Less than 1% of ip dose of NPYR appeared as n-nitroso-3-hydroxy-pyrrolidine in urine of rats. Alkylated base, which was not identified ... was isolated from hydrolysates of liver DNA. (3)h-NPYR administration to rats reacted with DNA and RNA; however, no products were characterized.|For more Metabolism/Metabolites (Complete) data for N-NITROSOPYRROLIDINE (25 total), please visit the HSDB record page.|NPYR has known human metabolites that include 2-Pyrrolidinol, 1-nitroso-.

ACUTE/CHRONIC HAZARDS: Flammable. (NTP, 1992)

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. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Nitrates, nitrites, and related compounds/|Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Anticipate seizures and treat as necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Nitrates, nitrites, and related compounds/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or is in severe respiratory distress. Monitor cardiac rhythm and treat arrhythmias if necessary. Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. If unresponsive to these measures, vasopressors may be helpful. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Nitrates, nitrites, and related compounds/

/GENOTOXICITY/ Liver S9 fractions were prepared from male and female Syrian Golden hamsters and Sprague-Dawley rats, 1, 3, 6, and 12 mo of age, which were either uninduced (corn-oil treated) or induced with Aroclor 1254 suspended in corn oil. These preparations were compared at varying protein levels for their ability to metabolize ... nitrosopyrrolidine ... to products mutagenic to Salmonella typhimurium. ... The greatest number of revertant colonies with nitrosopyrrolidine occurred with preparations from male hamsters. A decrease in numbers of revertant colonies with increasing age was observed with the S9 preparation from Arcolor-treated male rats. ... The only nitrosamine mutagenic with human liver S9 was nitrosopyrrolidine. All of the human preparations metabolized this carcinogen at similar levels. ...|/GENOTOXICITY/ The liver post-mitochondrial supernatants (S-9 mix) from 5 species including man (1 accident victim) were tested for activating activity with ... nitrosopyrrolidine in the Ames test. ... Nitrosopyrrolidine was activated by all but the rat; human S-9 mix was exceptionally activating for nitrosopyrrolidine. Enzyme levels in hepatic microsomes of all 5 species were determined and had no relation to S-9 mix metabolic activation ability.

N Nitrosopyrrolidine

Pyrrolidine, 1-nitroso-: ACTIVE|S - indicates a substance that is identified in a final Significant New Use Rule.

Method: NIOSH 2522, Issue 2; Procedure: gas chromatography with thermal energy analyzer; Analyte: N-nitrosopyrrolidine; Matrix: air; Detection Limit: 0.05 ug/sample.|Method: OSHA 27; Procedure: gas chromatography with thermal energy analyzer detection; Analyte: N-nitrosopyrrolidine; Matrix: air; Detection Limit: reliable quantitation limit 0.032 ppb (0.13 ug/cu m).|Method: EPA-RCA 8270D; Procedure: gas chromatography/mass spectrometry; Analyte: N-nitrosopyrrolidine; Matrix: solid waste matrices, soils, air sampling media and water; Detection Limit: 40 ug/L.|Procedure is described for determining N-nitrosopyrrolidine (NPYR) in bacon, beer & malt by gas chromatography-low resolution quadrupole mass spectrometry (GC-MS). Less than 100 ng of NPYR in total extract can be determined.|For more Analytic Laboratory Methods (Complete) data for N-NITROSOPYRROLIDINE (12 total), please visit the HSDB record page.

A method is described for the analysis of nitrosamines in aqueous solution and in biological fluids (blood, plasma, and rat liver microsomal suspensions). The method is based on photochemical degradation of the nitrosamine in a controlled environment to yield the corresponding amine and nitrite ion, and the latter is subsequently used to form a chromophoric or fluorescent product. ... With a colorimetric readout, the sensitivity for analysis of N-nitrosopyrrolidine was 800 ng/ml for a 5-ml sample and the measurement precision was +/- 6% in the biological fluids. Fluorometric analysis improved sensitivity to 4 ng/ml with a precision of +/- 10% in biological media.

Fire Hazards -> Carcinogens, Flammable - 2nd degree