Diethylnitrosamin

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.

Vapors are heavier than air and will collect in low areas. Vapors may travel long distances to ignition sources and flashback. Vapors in confined areas may explode when exposed to fire. Containers may explode in fire. Storage containers and parts of containers may rocket great distances, in many directions.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

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

Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage.

Color Code-Green: General storage may be used. Prior to working with this chemical you should be trained on its proper handling and storage. Store in tightly closed containers in a cool, dark, well-ventilated area away from light, oxidizers, reducing agents, hydrogen bromide. Where possible, automatically pump liquid from drums or other storage containers to process containers. Sources of ignition, such as smoking and open flames, are prohibited where this chemical is handled, used, or stored. Metal containers involving the transfer of 5 gallons or more of this chemical should be grounded and bonded. Drums must be equipped with self-closing valves, pressure vacuum bungs, and flame arresters. Use only nonsparking tools and equipment, especially when opening and closing containers of this chemical. Wherever this chemical is used, handled, manufactured, or stored, use explosion-proof electrical equipment and fittings. A regulated, marked area should be established where this chemical is handled, used, or stored in compliance with OSHA Standard 1910.1045.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practicable 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/

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Soak up with inert absorbent material and dispose of as hazardous waste. Keep in suitable, closed containers for disposal.

Evacuate and restrict persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Ventilate area of spill or leak. Absorb liquids in vermiculite, dry sand, earth, peat, carbon, or a similar material and deposit in sealed containers. Keep this chemical out of a confined space, such as a sewer, because of the possibility of an explosion, unless the sewer is designed to prevent the buildup of explosive concentrations. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Contact your local or federal environmental protection agency for specific recommendations. If employees are required to clean up spills, they must be properly trained and equipped. OSHA 1910.120(q) may be applicable.

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/

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/

SMALL SPILLS AND LEAKAGE: If you should spill this chemical, use absorbent paper to pick up all liquid spill material. Seal the absorbent paper, as well as any of your clothing which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Wash any surfaces you may have contaminated 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.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U174, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

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 available methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for N-Nitrosodiethylamine (10 total), please visit the HSDB record page.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

For more Preventive Measures (Complete) data for N-Nitrosodiethylamine (14 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.

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

For more Personal Protective Equipment (PPE) (Complete) data for N-Nitrosodiethylamine (6 total), please visit the HSDB record page.

Human blood was examined for the presence of volatile nitrosamines. Nitrosamines were detected by chemiluminescence and mass spectrometry after separation from blood by distillation and solvent extraction. N-Nitrosodimethylamine was detected in all but one of 51 blood samples taken from 23 different people, at concentrations from the detection limit (0.1 microgram/litre) to 1.4 microgram/litre with a mean concentration of 0.5 microgram/litre. N-Nitrosodiethylamine was detected in 11 samples, the detection limit being 0.1 microgram/litre. No other volatile nitrosamines were detected. After a test meal of bacon, spinach, bread and beer, the concentration of N-nitrosodimethylamine increased. There was no appreciable difference between the nitrosamine concentrations in the blood of laboratory workers and in the blood of other people. Salivary nitrite concentrations measured semi-quantitatively concurrently with blood sampling varied considerably but showed no apparent correlation with blood nitrosamine levels. Measurements in rabbits given a continuous infusion of N-nitrosodimethylamine gave a clearance rate approximately equal to the blood flow through the liver and a volume of distribution of 1.2 litre/kg body weight. By applying these results to man, the body burden after the meal was calculated as 40-50 microgram. This is substantially higher than the estimated weekly intake of volatile nitrosamines from food.

OBJECTIVE: The present paper aims to investigate the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and N-nitrosodiethylamine (DEN) on tumorigenesis and its potential mechanism. METHODS: The potentials of TCDD and DEN in separation or in combination to induce malignant transformation were tested in Balb/c 3T3 cells by using a cell transformation assay method. The possible mechanism of observed effects was studied further by adding a-naphthoflavone (a-NF), a competitive binding agent of TCDD, to the Aryl hydrocarbon receptor (AhR) pathway. The mRNA expressions of Cyp1a1 and Cyp2a5 gene in Balb/c 3T3 cells treated by DEN and TCDD in separation or in combination with or without presence of a-NF were measured with fluorescence quantification RT-PCR technique. RESULTS: The cell transformation frequency (TF) was significantly higher in case of induction with TCDD in combination with DEN, as compared to that with either TCDD or DEN alone. These effects were not inhibited via a-NF. The mRNA expression levels of both Cyp1a1 and Cyp2a5 were enhanced by TCDD treatment alone, but this inducible effect was blocked in cells treated by TCDD and DEN in combination. CONCLUSION: TCDD and DEN had a significant synergistic effect on tumorigenesis when they were used in combination. AhR pathway may not be the key mechanism of this synergistic effect. Thus, it is necessary to further test the potential mechanism involved in cancer development.

... In the present study, we examined the effects of pitavastatin - a drug used for the treatment of hyperlipidemia - on the development of diethylnitrosamine (DEN)-induced liver preneoplastic lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were administered tap water containing 40 ppm DEN for 2 weeks and were subsequently fed a diet containing 1 ppm or 10 ppm pitavastatin for 14 weeks. At sacrifice, feeding with 10 ppm pitavastatin significantly inhibited the development of hepatic premalignant lesions, foci of cellular alteration, as compared to that in the untreated group by inducing apoptosis, but inhibiting cell proliferation. Pitavastatin improved liver steatosis and activated the AMPK-alpha protein in the liver. It also decreased free fatty acid and aminotransferases levels, while increasing adiponectin levels in the serum. The serum levels of tumor necrosis factor (TNF)-alpha and the expression of TNF-alpha and interleukin-6 mRNAs in the liver were decreased by pitavastatin treatment, suggesting attenuation of the chronic inflammation induced by excess fat deposition.

Resveratrol, a phytochemical compound abundant in red wine and grapes, is known to affect cancer cells both in vitro and in vivo. ... This study reports the effects of resveratrol in the early and advanced stages of hepatocarcinogenesis in a model of N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) of male Wistar rats. For the experiment, rats were divided into different groups and treated with resveratrol either from day 1 of DEN administration for 15 days (pre-HCC), or after the development of HCC, i.e., 15-16 weeks after DEN administration (post-HCC), and compared to untreated HCC-bearing rats. Biochemical analysis of alpha-fetoprotein, the known serum marker for HCC, and other serum and liver marker enzymes also demonstrated a decreased level upon resveratrol treatment compared to the untreated HCC-bearing rats. H and E staining of tissue sections from the liver showed alteration or transformation of liver parenchymatous tissue in DEN-induced HCC (at 15-16 weeks). Resveratrol treatment during early (on day 1 of DEN-induction) and advanced (weeks 17-18) HCC showed a marked difference in the tissue architecture compared to untreated HCC. Immunoblot analysis revealed that resveratrol intervention at both the early and advanced stages of DEN-induced HCC activated the apoptotic markers, such as PARP cleavage, caspase-3 activation, p53 up-regulation and cytochrome-c release. In addition, semiquantitative RT-PCR and immunoblot analysis demonstrated the up- and down-regulation of key apoptotic regulators, such as Bax and Bcl2, respectively, in a resveratrol treatment-dependent manner. ...

The chemopreventive potential of Tephrosia purpurea extract (TPE) on N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma (HCC) in Wistar rats was assessed. HCC was induced by a single intraperitoneal injection of NDEA (200 mg/kg) followed by subcutaneous injections of CCl(4) (3 mL/kg per week) for six weeks. After administration of the carcinogen, 200 and 400 mg/kg TPE were administered orally once a day throughout the study. The levels of liver cancer markers, including alpha-fetoprotein and carcinoembryonic antigen, were substantially increased by NDEA treatment. TPE treatment significantly reduced liver injury and restored the entire liver cancer markers. Additionally, TPE markedly normalized the activity of antioxidant enzymes, namely lipid peroxidation, reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase in the liver of NDEA-treated rats. Treatment with TPE significantly reduced the nodule incidence and multiplicity in the carcinogen-bearing rats. Histological observations of the liver tissues correlated with the biochemical observations. These findings powerfully support that T. purpurea prevented lipid peroxidation, suppressed the tumor burden, and promoted enzymatic and nonenzymatic antioxidant defence systems during NDEA-induced hepatocarcinogenesis. This might have been due to modulating the antioxidant defense status, which contributed to its anticarcinogenic potential.

For more Interactions (Complete) data for N-Nitrosodiethylamine (16 total), please visit the HSDB record page.

EC50; Species: Anabaena flosaquae (Blue-Green Algae) 10000 cells; Conditions: freshwater, static, 24 °C; Concentration: 17.5 mg/L for 96 hr; Effect: growth, general

EC50; Species: Pseudokirchneriella subcapitata (Green Algae) 10000 cells; Conditions: freshwater, static, 24 °C; Concentration: 10.2 mg/L for 96 hr; Effect: growth, general

LC50; Species: Gammarus limnaeus (Scud); Conditions: freshwater, renewal, 19.5-20.0 °C, pH 8.10-8.24, hardness 260 mg/L CaCO3, dissolved oxygen 6.9-8.0 mg/L; Concentration: 500 mg/L for 96 hr (95% confidence interval: 424-590 mg/L)

LC50; Species: Pimephales promelas (Fathead Minnow); Conditions: freshwater, static, 22.0-23.0 °C, pH 8.07-8.25, hardness 288 mg/L CaCO3, dissolved oxygen 4.8-7.0 mg/L; Concentration: 775 mg/L for 96 hr (95% confidence interval: 698-860 mg/L)

For more Ecotoxicity Values (Complete) data for N-Nitrosodiethylamine (6 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that N-nitrosodiethylamine is expected to have high mobility in soil(SRC). Volatilization of N-nitrosodiethylamine from moist soil surfaces is expected(SRC) given a Henry's Law constant of 3.63X10-6 atm-cu m/mole(3). Studies show that when applied to soil surface, 30 to 80% of the N-nitrosodiethylamine may be lost during the first few hours(4). When incorporated 7.5 cm in Matapeake loam soil (water at field capacity, 26%) 11% and 21% volatilized at 20 and 35 °C, respectively, most of which occurred within 2 days(4). N-Nitrosodiethylamine is susceptible to direct photolysis in sunlight(SRC) due to its strong absorption of UV light above 290 nm (an absorption max at 330 nm) and quantum yield of 0.43(5); therefore, N-nitrosodiethylamine is expected to photolyze on soil surfaces exposed to sunlight(SRC). 14C-N-Nitrosodiethylamine mineralized approximately 50% and volatilized 11% from Matapeake loam soil incubated at 30 °C for 20 days(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that N-nitrosodiethylamine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon a Henry's Law constant of 3.63X10-6 atm-cu m/mole(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 10 and 80 days, respectively(SRC). The concentration of N-nitrosodiethylamine (18.0 ppm nitroso-N) in lake water was essentially unchanged after 108 days incubation in the dark at 30 °C(5), indicating that hydrolysis and biodegradation are not expected(SRC). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow of 0.48(7) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. Direct photolysis in water is expected based on a rate constant of 0.045/min with a half-life of 15 minutes for N-nitrosodiethylamine in aqueous solution exposed to irradiation representing Southern California midsummer, midday sun(8). When exposed to sunlight for 7 hours at 33-35 °C, the photolysis of a N-nitrosodiethylamine solution was 88.7% complete(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), N-nitrosodiethylamine, which has a vapor pressure of 0.86 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase N-nitrosodiethylamine 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). N-Nitrosodiethylamine absorbs UV light strongly above 290 nm with an absorption max at 330 nm and a quantum yield of 0.43(4) which indicates a susceptibility for direct photolysis in sunlight(SRC). N-Nitrosodiethylamine's half-life in a Teflon outdoor smog chamber irradiated with sunlight was 1 to 2 hrs(5).

Of 24 samples of cheese, meat and fish analyzed for N-nitrosodiethylamine, 5 contained 1.5 ug/kg and one contained trace level (0.5-1.0 ug/kg)(1). In a preliminary survey of the Italian market, the concentrations of N-nitrosodiethylamine in canned luncheon meats and cured meats were <0.3-62.80 and <0.3-11.01 ppb, respectively(2). The food item with the highest concentration was pork with jelly(2). No N-nitrosodiethylamine was detected in 38 samples of cooking oils, 10 of butter, and 14 of margarine purchased in 1974 from retail stores in Ottawa, Canada(3). Cured meat stored in elastic rubber netting may pick up N-nitrosodiethylamine as a result of the interaction of the amine precursors (e.g., dithiocarbamates) in the rubber and nitrite additive commonly used in the preparation of the cured meat(4). For example, a smoked ham stored in rubber netting contained 6.9 ppb of N-nitrosodiethylamine in the outer layer, 4.9 ppb in the next layer and 0.8 ppb in the center(4). A N-nitrosodiethylamine concentration of 3 ppb was found in beer(5). When rubber nipples were sterilized in a manner typical of home use, N-nitrosodiethylamine in the rubber nipples migrated into water, milk, and infant formula(6).

IDENTIFICATION AND USE: N-nitrosodiethylamine (NDEA) is a yellow oil. It is used as a gasoline and lubricant additive, antioxidant and as a stabilizer in plastics. HUMAN STUDIES: NDEA has been identified as tobacco carcinogen. Short-term exposure of a bronchial epithelial cell line to smoking-equivalent concentrations of tobacco carcinogens including NDEA altered the expression of key proliferation regulatory genes, EGFR, BCL-2, BCL2L1, BIRC5, TP53, and MKI67, similar to that reported in biopsy specimens of pulmonary epithelium described to be preneoplastic lesions. ANIMAL STUDIES: NDEA caused tumors in several species of experimental animals, at several different tissue sites, and by several different routes of exposure. It was carcinogenic in animals exposed perinatally and as adults, causing tumors mainly in the liver, respiratory tract, kidney, and upper digestive tract. Benign and malignant liver tumors occurred in mice, rats, hamsters, guinea pigs, rabbits, dogs, and pigs orally exposed to NDEA. Liver tumors also occurred in rats following inhalation exposure or rectal administration; in mice, rats, and hamsters following intraperitoneal injection; in hamsters, guinea pigs, gerbils, and hedgehogs following subcutaneous injection; in mice following prenatal exposure; in birds following intramuscular injection; and in fish and frogs exposed to NDEA in the tank water. In dogs, exposure to NDEA by stomach tube followed by subcutaneous injection caused cancer of the liver and nasal cavity. Tumors of the lung and upper respiratory tract occurred in mice, rats, hamsters, dogs, and pigs following oral administration of NDEA. Tumors of the kidney occurred in rats following oral, intravenous, or prenatal administration of NDEA. Oral administration also caused kidney tumors in pigs and tumors of the upper digestive tract in mice, rats, and hamsters. The mutagenicity of NDEA was evaluated in Salmonella tester strains TA98, TA100, TA1535, TA1537 and TA1538 (Ames Test), both in the presence and absence of added metabolic activation. NDEA did not cause a reproducible positive response in any of the bacterial tester strains, either with or without metabolic activation. In the presence of liver microsomal fraction from phenobarbital-treated rats, NDEA caused 8-azaguanine-resistant mutants in Chinese hamster V79 cells. NDEA was mutagenic in recessive lethal test in Drosophila melanogaster. The effects of NDEA on sexual development, gametogenesis, and oocyte maturation were studied in Japanese medaka (Oryzias latipes). NDEA reduced the germ cell number dose-dependently during early stages of sexual differentiation in XX larvae, resulting in underdeveloped ovaries in adulthood at low doses. This effect was sex-specific as no such changes were seen in XY larvae. Furthermore, XX and XY larvae that were exposed at a low dose during early life showed a significant reduction in body weight in adulthood. Gonads in sexually immature adult medaka males and females exposed to NDEA were in advanced stages in comparison to that of the controls. ECOTOXICITY STUDIES: NDEA induced oxidative stress and antioxidant defense to zebrafish metabolism system at concentrations over 5 ug/L. After a 42-day exposure, a significant DNA damage was observed in zebrafish liver cells at NDEA concentrations beyond 500 ug/L. Toxic and carcinogenic effects observed in snakes (Phython reticulatus) after lifelong administration of 6, 12, and 24 mg/kg NDEA by gavage at four nightly intervals. Total dose needed to induce tumors was 500-600 mg/kg.

/AQUATIC SPECIES/ N-nitrosodiethylamine (NDEA) is one of the emerging nitrogenous disinfection byproducts with probable cytotoxicity, genotoxicity, and carcinogenesis. Its potential toxicological effects have received extensive attention but remain to be poorly understood. In this study, changes in NDEA precursors in drinking water treatment process were studied using the trial of its formation potential (FP), and the toxicity induced by NDEA to adult zebrafish was investigated. NDEA FP in the raw water of Taihu Lake ranged from 46.9 to 68.3 ng/L. The NDEA precursors were removed effectively by O3/BAC process. Hydrophilic fraction and low-molecular-weight fraction (<1 kDa) had the highest NDEA FP. The toxicity results demonstrated that the acute lethal concentration of NDEA causing 50% mortality in 96 hr (96-hr LC50) was 210.4 mg/L, and NDEA was more likely to be accumulated in kidney, followed by liver and gill. NDEA induced oxidative stress and antioxidant defense to zebrafish metabolism system at concentrations over 5 ug/L. After a 42-day exposure, a significant DNA damage was observed in zebrafish liver cells at NDEA concentrations beyond 500 ug/L. This study investigated NDEA properties in both engineering prospective and toxicity evaluation, thus providing comprehensive information on its control in drinking water treatment process and its toxicity effect on zebrafish as a model animal.

/AQUATIC SPECIES/ Diethylnitrosamine (DEN) is present in food, water, and daily supplies and is regarded as a toxicant of carcinogenicity. The developmental toxicity of DEN has been rarely reported as yet. In this study, zebrafish were exposed to different concentrations of DEN at 6 hr post-fertilization (hpf) to access embryonic toxicity of the compound. The results show that DEN resulted in negative effects of hatching rate, heartbeat, body length, and spontaneous movement. Deformities, including notochord malformation, pericardium edema, embryonic membrane turbidity, tail hypoplasia, yolk sac deformity, and growth retardation, happened during exposure period. Moreover, production of reactive oxygen species (ROS) significantly increased after DEN treatment. Then, alterations of the expression level of oxidative stress-related genes were observed... Development toxicity of DEN should be related to the excessive oxidative stress.

/OTHER TERRESTRIAL SPECIES/ Toxic and carcinogenic effects observed in snakes (Phython reticulatus) after lifelong administration of 6, 12, and 24 mg/kg /N-nitrosodiethylamine/ by gavage at four nightly intervals. Total dose needed to induce tumors was 500-600 mg/kg.

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for N-nitrosodiethylamine is available.[Available from, as of February 1, 2019: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of February 4, 2019: http://actor.epa.gov/dashboard/]

Chemical plant effluent released to a river contained 132 ng/L of N-nitrosodiethylamine(1). N-Nitrosodiethylamine was not detected (detection limit 25 ug/L) in primary sludge, waste-activated sludge or anaerobic digester mixed liquor samples collected from three wastewater treatment plants in the US(2).

N-Nitrosodiethylamine was detected (ug/L) in effluents flowing into rivers of the Jialu River basin in China. Not all sites were sampled on each date(1).[Table#4694]

U174; As stipulated in 40 CFR 261.33, when N-nitrosodiethylamine, 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).

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).

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

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 recommended criteria are 8.0 ng/L, 0.8 ng/L, and 0.08 ng/L, respectively. If these estimates are made 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.

Used as a gasoline and lubricant additive, an antioxidant, and a stabilizer in plastics; [Merck Index] Used as a research chemical; [HSDB]

Gasoline and lubricant additive; antioxidant; stabilizer in plastics.

Although NDEA is available in small quantities for research purposes, no evidence was found that it has been manufactured commercially.

(1977) NOT PRODUCED COMMERCIALLY IN USA

(1982) NOT PRODUCED COMMERCIALLY IN USA

(1978) Not produced commercially in the USA.

Formed by the interaction of nitrite with diethylamine, and by the action of nitrate reducing bacteria.

... laboratory synthesis of N-nitrosamines is the reaction of a secondary amine with acidic nitrite at ca pH 3. The primary nitrosating intermediate is N2O3 arising from nitrous acid. /N-nitrosamines/

Industrial preparationn: Reilly, German patent 1085166 (1960 to du Pont), ... Levering, Maury, United States of America patent 3090786 (1963 to Hercules Powder).