ジエタノールニトロソアミン

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 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/

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/

SPILLS OF N-NITROSODIETHYLAMINE CAN BE ABSORBED BY CELITE OR COMMERCIAL SPILL ABSORBANT. AFTER ABSORBANT CONTAINING MAJOR SHARE OF NITROSAMINE HAS BEEN PICKED UP (AVOID DUSTS; DO NOT SWEEP), SURFACE SHOULD BE THOROUGHLY CLEANED WITH STRONG DETERGENT SOLN. IF MAJOR SPILL OCCURS OUTSIDE OF VENTILATED AREA, ROOM SHOULD BE EVACUATED & CLEANUP OPERATION SHOULD BE CARRIED OUT BY PERSONS EQUIPPED WITH SELF-CONTAINED RESPIRATORS. THOSE INVOLVED IN THIS OPERATION SHOULD WEAR RUBBER GLOVES, LAB COATS, & PLASTIC APRONS OR EQUIVALENT PROTECTIVE APPAREL. /N-NITROSODIETHYLAMINE, ALSO APPLICABLE TO OTHER DIALKYLNITROSAMINES/

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/

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 U173, 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 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.

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

For more Disposal Methods (Complete) data for N-NITROSODIETHANOLAMINE (15 total), please visit the HSDB record page.

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

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

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

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

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

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

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent ... 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/

Initiating activity of N-nitrosodiethanolamine (NDELA) for rat liver carcinogenesis was investigated using an 8-weeks bioassay system. Male F344 rats were initially treated with a single intraperitoneal injection of NDELA at one of five dose levels: 1, 600, 800, 400, 200, or 100 mg/kg. Two weeks later, the rats were placed on 0.02% 2-acetylaminofluorene (2-AAF) or 0.05% phenobarbital (PB) containing diet for 6 weeks. All animals were subjected to 2/3 partial hepatectomy 4 weeks after the NDELA treatment, and killed at the end of the eighth week. NDELA itself exerted low toxicity in terms of body weight gain. Clear dose-dependent initiating activity of NDELA was observed in terms of development of glutathione S-transferase placental form (GST-P) positive liver cell foci, this being more apparent with PB promotion than with 2-AAF where the enhancing regimen itself caused multiple lesion development. Initiating potential of NDELA, however, was much lower than that observed for diethylnitrosamine in our previous work.

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.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that N-nitrosodiethanolamine is expected to have very high mobility in soil(SRC). Volatilization of N-nitrosodiethanolamine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.9X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(2). N-Nitrosodiethanolamine is not expected to volatilize from dry soil surfaces based on an estimated vapor pressure of 5.0X10-4 mm Hg at 20 °C(3). N-Nitrosodiethanolamine has a UV absorption max at 345 nm(4) which indicates that the compound may be susceptible to direct photolysis by sunlight(SRC). Biodegradation in soil may be slow(SRC), based upon N-nitrosodiethanolamine's slow biodegradation in two lake waters and sewage(5).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that N-nitrosodiethanolamine is not 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 4.9X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of -1.28(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. The direct photolysis rate constant for the analogous compound N-nitrosodiethylamine in aqueous solution exposed to irradiation representing Southern California midsummer, midday sun was observed to be 0.045/min with a half-life of 15 minutes and a quantum yield of 0.43(5); the photolysis rate of N-Nitrosodiethanolamine is expected to be similar(SRC). N-Nitrosodiethanolamine biodegraded slowly in samples of sewage and two lake waters(6). The fastest degradation of N-nitrosodiethanolamine in a lake water sample was in one taken in August; an initial concentration of 1.0 ug/mL was completely converted to soluble products in 9 days(6). However, no metabolism of N-nitrosodiethanolamine was observed after 32 days incubation at 22 °C in a lake water sample taken in January(6). In sewage, N-nitrosodiethanolamine was mineralized, but CO2 formation was not observed until about day 25; after 89 days over 40% of the carbon added as N-nitrosodiethanolamine was recovered as CO2 when the experiment was terminated(6).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), N-nitrosodiethanolamine, which has an estimated vapor pressure of 5.0X10-4 mm Hg at 20 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase N-nitrosodiethanolamine 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 13 hours(SRC), calculated from its rate constant of 3X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). N-Nitrosodiethanolamine has a UV absorption max at 345 nm(4) which indicates that N-Nitrosodiethanolamine may be susceptible to direct photolysis by sunlight(SRC).

N-Nitrosodiethanolamine was detected in suya, a popular indigenous meat product of Nigeria, at concentrations ranging from 0.25 to 0.36 mg/kg in raw meat, 1.28 to 1.89 mg/kg in pregrilled suya, and 0.87 to 1.22 mg/k in freshly grilled suya(1).

0.1-173 ug/kg NDELA /N-nitrosodiethanolamine was found/ in tobacco. Source was believed to be maleic hydrazide herbicide formulated as diethanolamine salt, which had been used on the tobacco.

N-Nitrosodiethanolamine isolated from tobacco varied in amount from 0.1 ppb in flue cured tobacco not treated with herbicide MH-30 (maleic hydrazide) to 173 ppb in burley tobacco to which herbicide was applied prior to harvesting.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of June 21, 2012: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=1116-54-7]

N-Nitrosodiethanolamine

Hepatic

PRECAUTIONS FOR "CARCINOGENS": ... In relation specifically to cancer hazards, there are at present no health monitoring methods that may ensure the early detection of preneoplastic lesions or lesions which may prelude them. Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning additional tests that might become useful or mandatory. /Chemical Carcinogens/

Using a structure estimation method based on molecular connectivity indices(1), the Koc of N-nitrosodiethanolamine can be estimated to be 1(SRC). According to a classification scheme(2), this estimated Koc value suggests that N-nitrosodiethanolamine is expected to have very high mobility in soil.

/HUMAN EXPOSURE STUDIES/ N-Nitroso compounds (nitrosamines) have been detected at the parts per billion level in a wide variety of matrices including industrial chemicals, pharmaceuticals, and food. Although N-nitrosodiethanolamine (NDELA) may be detected as an impurity in some cosmetic products, studies on NDELA absorption through human skin have been limited. A study to determine the extent of NDELA absorption following topical application was therefore undertaken to assist in the proper assessment of risk following unintended exposure. NDELA absorption was measured in vitro through human cadaver skin using isopropyl myristate (IPM) and generic prototype personal-care formulations (sunscreen and shampoo) spiked with (14)CNDELA. When applied as a finite dose at a concentration of 0.06% or lower, NDELA absorption was found to be a linear function of concentration. Total absorption at 48 hr ranged from approximately 35 to 65% of the dose and was formulation dependent (IPM > shampoo > or = sunscreen). Absorption occurred relatively rapidly from all formulations and peak rates of absorption were seen within the first 5 hr from the IPM and shampoo formulations. When applied as an infinite dose, total NDELA absorption followed a different rank order (shampoo > or = IPM > sunscreen) and evidence of barrier damage was seen with the shampoo formulation.

/GENOTOXICITY/ The effect of alcohol dehydrogenase (ADH/NAD) from yeast and horse liver was tested on the induction of chromosomal mutations and sister chromatid exchanges (SCE) by N-nitrosodiethanolamine (NDELA) in human lymphocyte cultures. BrdUrd (27 ug) was added 24 hr after starting the cultures to allow visualisation of SCE. ADH/NAD and NDELA were added 24 hr later in different concentrations. No significantly higher level of numerical or structural chromosome aberrations was observed. However, the SCE frequency per cell was significantly increased by adding NAD (31.25 mumol and 62.5 mumol). The exclusive addition of 220 units ADH from yeast as well as 1.8 units ADH from horse liver also raised the number of SCE highly significantly. The combination of NAD and ADH was more effective than each substances alone in the yeast but not in the horse liver system. NDELA in a range of 12.5-62.5 mumol, given to cultures with ADH/NAD from yeast, additionally increased the SCE frequencies in a dose-dependent way. Similar results were found in cultures containing ADH/NAD from horse liver and 6.25-31.25 mumol NDELA, but the total numbers of SCE were distinctly higher. These results indicate that NDELA is strongly activated by ADH from yeast but even more by ADH from horse liver.

/GENOTOXICITY/ In 28 smoking and 37 non-smoking male metal workers from 7 small to medium sized plants the genotoxic effect caused by the occupational exposure measured as DNA single strand breaks in the peripheral mononuclear blood cells was investigated. Metal workers using synthetic cutting fluids are possibly exposed to the carcinogenic N-nitrosodiethanolamine (NDELA). In this investigation NDELA was detected in the air of the working halls in a concentration up to 1000 ng/cu m and in the cutting fluids in a concentration up to 135 mg/L (mean values per plant). Workers staying in rooms with a mean concentration of NDELA in the air of about 1 microgram/cu m revealed two times more DNA strand breaks than workers staying in an environment with less than 50 ng/cu m of NDELA (p < 0.01). Non-smoking workers with more than 4.5 hr contact to cutting fluids per day showed an 1.5 times higher mean level of DNA strand breaks than their nonsmoking colleagues having had less than 4.5 hr contact to cutting fluids (p < 0.02). Also workers having had work place-related complaints showed a statistically significantly higher level of DNA strand breaks compared to workers with no or no work place-related complaints. No significant correlation was obtained between the extent of DNA damage and the estimated extent of skin contact or the concentration of NDELA found in the cutting fluids. Therefore, for workers in this investigation NDELA incorporated by inhalation is probably more relevant for genotoxic damage than NDELA resorbed by skin. An increased level of DNA damage was found in metal workers depending on the concentration of NDELA in the air of the work places. However, without further investigations it cannot be excluded that also other concomitant agents in the environment were responsible for the observed genotoxic effect.

U173; As stipulated in 40 CFR 261.33, when N-nitrosodiethanolamine, 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).

(a) Chemical substance and significant new use subject to reporting. (1) The chemical substance N-nitrosodiethanolamine (CAS No. 1116-54-7) is subject to reporting under this section for the significant new use described in paragraph (a)(2) of this section. (2) The significant new use is: Manufacture, import, or processing of 10,000 pounds or more per year per facility for any use.

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).

May contaminate cosmetics and cutting fluids; [Merck Index] Used as a research chemical; [HSDB]

Metal Machining [Category: Heat or Machine]

There is no known commercial use for N-nitrosodiethanolamine.

It is available in research quantities.

(1977) No Data

(1982) No Data

(1987) No Data

(1977) No Data

(1982) No Data

(1987) No Data

(1977) NOT PRODUCED COMMERCIALLY IN USA

(1982) NOT PRODUCED COMMERCIALLY IN USA

(1978) Not produced commercially in the USA

N-Nitrosodiethanolamine is formed by the action of nitrosating agents (nitrites; 2-bromo-2-nitropropane-1,3-diol; nitrogen oxides) on diethanolamine and triethanolamine. The rate of formation of N-nitrosodiethanolamine in aqueous solutions of ethanolamines is pH-, temperature- and time-dependent.

REACTION OF NITROUS ACID WITH DIETHANOLAMINE

N-Nitrosodiethanolamine has been prepared by the reaction of sodium nitrite with diethanolamine dissolved in dilute hydrochloric acid.

Ethanol, 2,2'-(nitrosoimino)bis-: ACTIVE

No evidence was found that NDELA has been produced commercially; it is difficult to prepare and purify.

2-BROMO-2-NITROPROPANE-1,3-DIOL (BNPD), AN ANTIBACTERIAL & ANTIFUNGAL AGENT, WAS SHOWN TO NITROSATE DIETHANOLAMINE & TRIETHANOLAMINE. AT PH 12.0 YIELD OF NDELA INCR FROM LESS THAN 1% AFTER 1 HR TO MAX OF 11% AFTER 96 HR.

N-Nitrosodiethanolamine (NDELA) was found in aq soln containing polysorbate 20 & diethanolamine stored at pH 6 & 50 °C under continuous aeration. ... NDELA was also formed in aq soln of hydrogen peroxide & diethanolamine.

The effect of various types of inhibitors with respect to structure & solubility on the formation of N-nitrosodiethanolamine (NDELA) was studied in prototype oil-in-water anionic emulsion. Nitrosation resulted from the action of nitrite on diethanolamine at pH 5.2-5.4. Among the water-sol inhibitors incorporated into the aq phase, sodium bisulfite & ascorbic acid were effective. Potassium sorbate was much less effective. The oil-sol inhibitors were incorporated into the oil phase of the emulsion. Of these, only ascorbyl palmitate was effective. When alpha-tocopherol was dispersed in the aq phase in the absence of the oil, nitrite was readily destroyed. The reduced inhibition obtained with butylated hydroxyanisole & alpha-tocopherol was at least in part because of their isolation from the nitrite in water phase. On the other hand, the reducing portion of the ascorbyl palmitate molecule could be in the water phase at the oil/water interface.