N-nitrosodiphenylamine

This chemical does not meet GHS hazard criteria for 1.9% (2 of 104) of reports.

H302 (48.1%): Harmful if swallowed [Warning Acute toxicity, oral]

H317 (51%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H351 (51%): Suspected of causing cancer [Warning Carcinogenicity]

H361 (37.5%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H361d (12.5%): Suspected of damaging the unborn child [Warning Reproductive toxicity]

H373 (51%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

H410 (50%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

H411 (37.5%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P203, P260, P261, P264, P270, P272, P273, P280, P301+P317, P302+P352, P318, P319, P321, P330, P333+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 104 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 2 of 104 reports by companies.

There are 10 notifications provided by 102 of 104 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

H320: Causes eye irritation [Warning Serious eye damage/eye irritation]

H351: Suspected of causing cancer [Warning Carcinogenicity]

H371: May cause damage to organs [Warning Specific target organ toxicity, single exposure]

H373: May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

H401: Toxic to aquatic life [Hazardous to the aquatic environment, acute hazard]

H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P203, P260, P264, P264+P265, P270, P273, P280, P305+P351+P338, P308+P316, P318, P319, P337+P317, P391, P405, and P501 (click each P-code to see the statement)

H302: Harmful if swallowed [Warning Acute toxicity, oral]

H315: Causes skin irritation [Warning Skin corrosion/irritation]

P203, P260, P264, P264+P265, P270, P280, P301+P317, P302+P352, P305+P351+P338, P308+P316, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P405, and P501 (click each P-code to see the statement)

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

H411: Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P264, P270, P273, P301+P317, P330, P391, and P501 (click each P-code to see the statement)

Fresh air, rest. Refer for medical attention.

Remove contaminated clothes. Rinse and then wash skin with water and soap.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Refer for medical attention .

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. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

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)

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Use foam, powder, carbon dioxide.

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.

Excerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]:

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 the immediate precautionary measure distance, in the downwind direction, as necessary.

FIRE: If tank, rail tank car or highway tank 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, 2024)

Do NOT let this chemical enter the environment. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting.

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. 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: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Decontamination of N-nitrosamine contaminated glassware /was described/. /N-nitrosamines/

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/

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

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

Incineration: Pour or sift onto a thick layer of sand and soda ash mixture (90-10). Mix and shovel into a heavy paper box with much paper packing. Burn in an incinerator. Fire may be augmented by adding excelsior and scrap wood. Waste may be dissolved in flammable solvent (alcohols, etc) and sprayed into fire box of an incinerator with afterburner and scrubber.

(1) Nitrosamines may be reduced to the corresponding amine by using nickel-aluminum (Ni-Al) alloy in dilute base. The nitrosamines were completely degraded (99.9%) and only the amines (RR'NH) were found in the final reaction mixtures. No traces (generally <0.1%) of the corresponding, possibly carcinogenic, hydrazines (RR'NNH2) were found in the final reaction mixtures. (2) Nitrosamines may be oxidized by potassium permanganate in 3 M sulfuric acid (KMnO4 in H2SO4). The nitrosamines were completely destroyed (>99.5%). The products of this reaction have not been determined. (3) Nitrosamines may be destroyed by using hydrogen bromide (HBr) in glacial acetic acid. The nitrosamines were completely destroyed (>99%) and the products were presumably the corresponding amines. All of these procedures were validated by an international collaborative study. /Nitrosamines/

For more Disposal Methods (Complete) data for N-Nitrosodiphenylamine (9 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 and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. 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-Nitrosodiphenylamine (14 total), please visit the HSDB record page.

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and 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 absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

STORAGE PRECAUTIONS: You should keep this material in a tightly closed container under an inert atmosphere, and store it at refrigerated temperatures. (NTP, 1992)

Separated from strong oxidants. Store in an area without drain or sewer access.

Keep container tightly closed in a dry and well-ventilated place. Store under inert gas. Air sensitive.

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

5.5 [mg/m3]

60 [mg/m3]

360 [mg/m3]

carcinogen category: 3

Evaporation at 20 °C is negligible; a harmful concentration of airborne particles can, however, be reached quickly when dispersed.

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

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: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

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

NO open flames.

Use local exhaust or breathing protection.

Protective gloves.

Wear safety goggles.

Do not eat, drink, or smoke during work.

N-nitrosodiphenylamine appears as yellow to brown or orange powder or flakes or a black solid. Insoluble in water and denser in water. Hence sinks in water. (NTP, 1992)

Yellow to brown or orange powder or flakes or a black solid; [CAMEO]

YELLOW FLAKES.

Yellow to brown or orange powder or flakes or a black solid.

Yellow plates from ligroin

Yellow plates or green crystals

Yellow plates from petroleum ether

151.7 °F (NTP, 1992)

151.7 °F

less than 1 mg/mL at 66 °F (NTP, 1992)

In water, 35 mg/L at 25 °C

In water, 35.09 mg/L at 25 °C

Slightly soluble in ethanol, chloroform; soluble in benzene

Soluble in acetone, ethylene dichloride; somewhat soluble in gasoline; 10% in ethanol; 10% in benzene

Solubility in water: none

1.23 (NTP, 1992) - Denser than water; will sink

1.23 g/cm³

1.23 @25 °C

0.00007 [mmHg]

log Kow = 3.13

2.57/3.13

Stable under recommended storage conditions.

Hazardous decomposition products formed under fire conditions - Carbon oxides, nitrogen oxides (NOx).

Energy of decomposition (in range 300-500 °C) measured as 0.65 kJ/g.

When heated to decomp it emits highly toxic fumes of ... /nitrogen oxides/.

Chemical shift

Crystal structure

Diamagnetic susceptibility

Formula unit

Lineshape

Magnetic susceptibility

Space group

Unit cell

Unit cell parameter

Nitrogen Compounds -> Nitrosamines

Carcinogens

Semi-Volatile Organic Compound (SVOC)

Pesticide -> EPA IRIS

Insoluble in water.

Azo, Diazo, Azido, Hydrazine, and Azide Compounds

Nitro, Nitroso, Nitrate, and Nitrite Compounds, Organic

N-NITROSODIPHENYLAMINE may be sensitive to moisture at elevated temperatures in strongly acidic solutions. May react vigorously with oxidizing agents. May undergo trans-nitrosation reactions with secondary amines (NTP, 1992).

Incompatible materials: Copper salts, mercury salts, strong mineral acids, strong oxidizing agents.

CDC-ATSDR Toxicological Profile

IDENTIFICATION AND USE: N-nitrosodiphenylamine (NDPHA) is a solid. NDPHA is an effective radical scavenger, and can be used to stabilize monomers, polymers and petroleum products. In rubber processing, its major use is believed to be as an anti-scorching agent, or vulcanization retarder, during rubber compounding. It is also used to make p-nitrosodiphenylamine. HUMAN STUDIES: NDPHA did not induce unscheduled DNA synthesis in human foreskin fibroblasts treated with up to 400 ug/mL. ANIMAL STUDIES: In an acute study of hepatotoxicity, mice given 350 mg/kg/day of NDPHA for 4 consecutive days preceding, or one dose 24 hours prior to, pentobarbital administration had effects characteristic of liver enzyme induction. In another study, rats and mice were fed diets containing up to 46000 mg/kg NDPHA for seven or 11 weeks. Female rats did not survive doses greater than 16000 mg/kg of diet; female mice survived higher doses. Male rats and male mice were not killed by the highest doses tested (10000 and 22000 mg/kg of diet, respectively). Rats were exposed to NDPHA by dietary feed at concentrations of 0, 250, 1000, 2000, 3000 or 4000 ppm for 5 days, 2, 4 and 13 weeks duration. There were no NDPHA exposure-related clinical signs of toxicity. NDPHA at a dose of 250 ug/mL did not induce DNA repair in Escherichia coli in the presence of metabolic activation. In several studies, doses of up to 2500 ug/plate NDPHA did not induce reversions in Salmonella typhimunum strains TA98, TA100, TA1535, TA1536, TA1537, TA 1538, G46, C3076 or 03052 in the presence of metabolic activation.

N-Nitrosodiphenylamine

Semi-Volatile Organic Compound (SVOC)

Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

No data are available in humans. Limited evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.

CLASSIFICATION: B2; probable human carcinogen - based on sufficient evidence of carcinogenicity in animals. BASIS FOR CLASSIFICATION: Increased incidence of bladder tumors in male and female rats and reticulum cell sarcomas in mice, and structural relationship to carcinogenic nitrosamines.

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 27: (1982) Some Aromatic Amines, Anthraquinones and Nitroso Compounds, and Inorganic Fluorides Used in Drinking-water and Dental Preparations

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

TR-164: Bioassay of N-Nitrosodiphenylamine for Possible Carcinogenicity (CASRN 86-30-6) (1979 )

12/13/78

Clear Evidence

No Evidence

It is concluded that under the conditions of this bioassay, N-nitrosodiphenylamine was carcinogenic for both sexes of F344 rats, including transitional-cell carcinomas of the urinary bladder, but was not carcinogenic for B6C3F1 mice of either sex.

The substance can be absorbed into the body by ingestion.

Body Weight

n-Nitrosodiphenylamine

PDF Document

See the IRIS entry for n-Nitrosodiphenylamine

PPRTV Archive

IRIS Current

LD50 Mouse ip 1000 mg/kg

LD50 Mouse oral 1860 mg/kg

LD50 Mouse oral 3,850 mg/kg

LD50 Rat oral 1825 mg/kg

LD50 Rat oral 3000 mg/kg bw

The mutagenicity of the carcinogen N-nitrosodiphenylamine (NDPhA) to Salmonella typhimurium TA98 was demonstrated only when norharman, a comutagen, was added to the incubation mixture with S9 mix. N,N-Diphenylamine (DPhA), a denitrosated derivative of NDPhA, was also mutagenic to S. typhimurium TA98 when norharman was present. Twice as many revertants were induced by DPhA with norharman as by NDPhA with norharman. The comutagenic effect of norharman was also observed with N-nitroso-methylphenylamine (NMPhA), N-nitrosoethylphenylamine (NEPhA) and N-nitrosophenylbenzylamine (NPhBeA) and their denitrosated derivatives. NDPhA was converted metabolically to DPhA by S9 mix. Stoichiometric studies indicated that the mutagenicity of NDPhA in the presence of norharman was exerted through DPhA. The denitrosation eyzme activity of NDPhA was mainly recovered in the microsomal fraction, and the enzyme seemed to be a cytochrome P-450 monooxygenase system. Denitrosation reactions of NMPhA, NEPhA and NPhBeA were also demonstrated. The mutagenicities of these compounds with norharman are therefore suggested to be due to a mechanism similar to that of NDPhA with norharman.

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 the 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. /Organic bases/Amines 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 pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if 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 patent can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . Cover skin burns with dry sterile dressings after decontamination ... . /Organic bases/Amines and related compounds/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Monitor cardiac rhythm and treat arrhythmias as 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 patient is unresponsive to these measures, vasopressors may be helpful. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen ... . Treat seizures with diazepam (Valuim) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Organic bases/Amines and related compounds/

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/

For more Antidote and Emergency Treatment (Complete) data for N-Nitrosodiphenylamine (6 total), please visit the HSDB record page.

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

/GENOTOXICITY/ N-Nitrosodiphenylamine did not induce unscheduled DNA synthesis in human foreskin fibroblasts treated with up to 400 ug/mL ... .

/ALTERNATIVE and IN VITRO TESTS/ Disinfection by-products (DBPs) in drinking water have caused worldwide concern due to their potential carcinogenic effects. The formation of phenazine from diphenylamine (DPhA) chloramination was studied and its cytotoxicities for two human cancer cells were also investigated. Phenazine was detected synchronously with the consumption of DPhA by chloramination, which further confirmed that the new DBP phenazine can be produced along with N-nitrosodiphenylamine (NDPhA) from DPhA chloramination. The formation of phenazine had a maximum molar yield with solution pH increasing from 5.0 to 9.0, with phenazine as the main product for DPhA chloramination at lower pH, but higher pH favored the formation of NDPhA. Thus, solution pH is the key factor in controlling the formation of phenazine and NDPhA. Both the initial DPhA and chloramine concentrations did not show a significant effect on the molar yields of phenazine, although increasing the chloramine concentration could speed up the reaction rate of DPhA with chloramines. The cytotoxicity assays showed that phenazine had significant cell-specific toxicity towards T24 (bladder cancer cell lines) and HepG2 (hepatic tumor cell lines) cells with IC50 values of 0.50 and 2.04 mmol/L, respectively, and T24 cells being more sensitive to phenazine than HepG2 cells. The IC50 values of phenazine, DPhA, and NDPhA for T24 cells were of the same order of magnitude and the cytotoxicity of phenazine for T24 cells was slightly lower than that of NDPhA (IC50, 0.16 mmol/L), suggesting that phenazine in drinking water may have an adverse effect on human health.

/LABORATORY ANIMALS: Acute Exposure/ In an acute study of hepatotoxicity, mice given 350 mg/kg/day of N-nitrosodiphenylamine for 4 consecutive days preceding, or one dose 24 hours prior to, pentobarbital administration had effects characteristic of liver enzyme induction. These effects consisted of significantly decreased pentobarbital sleeping time and increased amounts of smooth endoplasmic reticulum among granules of glycogen in the liver cell. Electron microscopy also revealed blebs, hypertrophy, and pleomorphism of the mitochondria. A NOAEL of 350 mg/kg/day was identified for hepatic effects, since light microscopy examination did not reveal hepatic lesions.

/LABORATORY ANIMALS: Acute Exposure/ The present study investigates the influence of different chemical structure of N-nitroso compounds on the hepatic level of reduced glutathione (GSH), glutathione reductase (GSH-R) and glutathione S-transferase (GST) activities in the liver of male Balb/C mice after treatment with 20 mg/kg body weight of each compound for 1 hr as a single dose. The level of reduced glutathione decreased significantly between 37 and 70% after the treatment of male mice with ethylbutylnitrosamine (-37%), diphenylnitrosamine (-50%), propylbutylnitrosamine (-52%), diethylnitrosamine (-54%), ethylmethylnitrosamine (-55%), and dibutylnitrosamine (-70%), whereas methylpropylnitrosamine increased the level of reduced glutathione by 71%. All the N-nitrosamine compounds tested increased the activity of glutathione reductase except ethylmethylnitrosamine had no effect. The activity of glutathione S-transferase activity was inhibited after treatment of the male mice with diphenylnitrosamine (-60%), dibutylnitrosamine (-60%), and methylpropylnitrosamine (-81%), while, ethylmethylnitrosamine and ethylbutylnitrosamine had no effect on such activity. On the other hand, diethylnitrosamine increased the activity of glutathione S-transferase by 50%. It can be postulated from this study that the chemical structure of N-nitrosamines plays a significant role in the alteration of reduced glutathione level and reduced glutathione metabolizing enzymes, since the substitution of different groups on the nitroso group was found to be capable of causing an alteration in such activities.

/LABORATORY ANIMALS: Acute Exposure/ The bioactivation of N-nitrosamines and polycyclic aromatic hydrocarbons (PAH) is mediated by the mixed function oxidase system, which includes dimethylnitrosamine N-demethylase I (DMN-dI), arylhydrocarbon hydroxylase (AHH), cytochrome P-450, cytochrome b5 and NADPH-cytochrome c reductase of liver microsomes. The present study shows the influence of N-nitroso compounds on the activities of the above-mentioned enzymes. Single-dose treatment (20 mg/kg body weight) of male mice with ethylbutylnitrosamine, propylbutylnitrosamine, or dibutylnitrosamine: increased (1) the activity of dimethylnitrosamine N-demethylase I by 108%, 104%, 51%, respectively; (2) the cytochrome P-450 content by 106%, 72%, 51%, respectively; (3) the activity of arylhydrocarbon hydroxylase by 95%, 106%, 80% respectively; (4) the cytochrome b5 content by 164%, 97%, 94% respectively; and (5) decreased the activity of NADPH-cytochrome c reductase by 55%, 50% and 45%, respectively. Methylpropylnitrosamine decreased the activity of dimethylnitrosamine N-demethylase I by 44% and the P-450 content by 50%. Diphenylnitrosamine also decreased cytochrome P450 by 54%, arylhydrocarbon hydroxylase activity by 64% but increased the activity of dimethylnitrosamine N-demethylase I by 42%, the cytochrome b5 content by 159% and NADPH-cytochrome c reductase activity by 57%. It seems from this study that the activity of arylhydrocarbon hydroxylase is dependent on P-450 content but dimethylnitrosamine N-demethylase I is not since the compounds that increased or decreased the activity of arylhydrocarbon hydroxylase had parallel effects on P-450 content. Also, the extent to which the altered activities of dimethylnitrosamine N-demethylase I, P-450, arylhydrocarbon hydroxylase, cytochrome b5 and NADPH-cytochrome c reductase depends on the type of alkyl groups linked to the nitroso group.

/LABORATORY ANIMALS: Acute Exposure/ The state of the xenobiotic biotransformation system has been studied after a single per os administration of diphenylamine (DPA) and N-nitrosodiphenylamine (NDPA) to male albino rats. ... There was an increase in the total content of cytochrome P-450 and the activity of NADPH-cytochrome P-450 reductase as well as a marked elevation of activity of microsomal glutathione S-transferase. This was paralleled with the induction of activity of individual isoenzymes of the multifunctional family of rat liver cytosol glutathione S-transferases and increased activity of glutathione reductase. ... Diphenylamine /stimulated/ the activity of both membrane-bound and soluble glutathione S-transferases. ...

LC50; Species: Daphnia magna (Water flea) age < or = 24 hr; Conditions: freshwater, static; Concentration: 7.8 mg/L for 48 hr (95% confidence interval: 5.8-11 mg/L) /> or =80% purity/

LC50; Species: Daphnia magna (Water flea) age < or = 24 hr; Conditions: freshwater, static; Concentration: >46 mg/L for 24 hr /> or =80% purity/

LC50; Species: Lepomis macrochirus (Bluegill) young of year; Conditions: freshwater, static; Concentration: 44 mg/L for 24 hr /> or =80% purity commercial grade/

LC50; Species: Lepomis macrochirus (Bluegill) young of year; Conditions: freshwater, static; Concentration: 5.8 mg/L for 96 hr (95% confidence interval: 4.8-7.6 mg/L) /> or =80% purity commercial grade/

LC50; Species: Eisenia fetida (Earthworm) adult; direct application 151 mg/kg (95% confidence interval: 136-167 mg/kg) /> or =98% purity/

1.10e+02

4.70e+02

1.10e+00

4.70e+00

1.20e+01

1.00e+03

6.70e-02

4.90e-03

Volatile

1.10e+04

4.70e+04

1.20e+03

The substance is toxic to aquatic organisms. Bioaccumulation of this chemical may occur in fish. It is strongly advised not to let the chemical enter into the environment.

N-Nitrosodiphenylamine's production and use as a rubber processing chemical and to make p-nitrosodiphenylamine may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 7X10-5 mm Hg at 25 °C indicates N-nitrosodiphenylamine will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase N-nitrosodiphenylamine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 16 hours. Particulate-phase N-nitrosodiphenylamine will be removed from the atmosphere by wet or dry deposition. N-Nitrosodiphenylamine absorbs minimal amounts of light at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, N-nitrosodiphenylamine is expected to have low mobility based upon a reported Koc of 1200. Volatilization from moist soil surfaces is expected based upon an estimated Henry's Law constant of 1.2X10-6 atm-cu m/mole. N-Nitrosodiphenylamine is not expected to volatilize from dry soil surfaces based upon its estimated vapor pressure. Degradation of N-nitrosodiphenylamine in soil is expected based on a studies where 68% was degraded by the end of a 30 day incubation at 30 °C in the dark. In soil amended with wheat straw, N-nitrosodiphenylamine disappeared completely by day 10 of the incubation. If released into water, N-nitrosodiphenylamine is expected to adsorb to suspended solids and sediment based upon the Koc. Biodegradation was fairly rapid in a static biodegradation test that used domestic wastewater as the inoculum. In a general study, it was determined that nitrosamines are rapidly decomposed by photolysis and do not persist in water illuminated in sunlight. Volatilization from water surfaces is expected based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 43 and 320 days, respectively. A maximum BCF of 217 measured in fish suggests bioconcentration in aquatic organisms is high. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to N-nitrosodiphenylamine may occur through inhalation and dermal contact with this compound at workplaces where N-nitrosodiphenylamine is produced or used. (SRC)

N-Nitrosodiphenylamine has not been reported to occur as a natural product(1).

N-Nitrosodiphenylamine's production and use as a rubber accelerator(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), a reported Koc value of 1200(2), indicates that N-nitrosodiphenylamine is expected to have low mobility in soil(SRC). Volatilization of N-nitrosodiphenylamine from moist soil surfaces may occur(SRC) given an estimated Henry's Law constant of 1.2X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). N-Nitrosodiphenylamine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). N-Nitrosodiphenylamine, added to soil at a concentration of 354 ug/g soil, was degraded 68% by the end of a 30 day incubation at 30 °C in the dark(4). In soil amended with wheat straw, N-nitrosodiphenylamine disappeared completely by day 10 of the incubation(5).

AQUATIC FATE: Based on a classification scheme(1), a reported Koc value of 1200(2), indicates that N-nitrosodiphenylamine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 1.2X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 43 and 320 days, respectively(SRC). N-Nitrosodiphenylamine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). According to a classification scheme(5), a maximum BCF of 217, measured in bluegill sunfish(6), suggests bioconcentration in aquatic organisms is high. Biodegradation was fairly rapid in a static biodegradation test that used domestic wastewater as the inoculum(7). N-Nitrosodiphenylamine biodegradation in the original culture and first, second and third subcultures after 7 days incubation per culture was: (10 mg/L initial concentration N-nitrosodiphenylamine) 47, 63, 95, and 98%; at 5 mg/L initial concentration N-nitrosodiphenylamine degradation was 87, 100, 92, and 100%, respectively(7). N-Nitrosodiphenylamine may photo-degrade in water based on structurally similar nitrosoamines that have degradation half-lives of 12-16 hours(8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), N-nitrosodiphenylamine, which has an estimated vapor pressure of 7X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase N-nitrosodiphenylamine 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 16 hours(SRC), calculated from its rate constant of 2.5X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase N-nitrosodiphenylamine may be removed from the air by wet or dry deposition(SRC). N-Nitrosodiphenylamine absorbs minimal amounts of light at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

AEROBIC: The half-life of N-nitrosodiphenylamine in 86 g sludge/kg soil produced from a wood preserving process was determined to be 88.9 days, from an initial concentration of 697 mg/kg and a final concentration of 19 mg/kg after 287 days; the half-life of N-nitrosodiphenylamine in 172 g sludge/kg soil produced from a wood preserving process was determined to be 166.4 days, from an initial concentration of 887 mg/kg and a final concentration of 58 mg/kg after 287 days(1). In a static biodegradation test that used domestic wastewater as the inoculum, the N-nitrosodiphenylamine biodegraded in the original culture and first, second and third subcultures after 7 days incubation per culture was: (10 mg/L initial concentration N-nitrosodiphenylamine) 47, 63, 95, and 98%; at 5 mg/L initial concentration N-nitrosodiphenylamine: 87, 100, 92, and 100%, respectively(2). Removal of N-nitrosodiphenylamine at two industrial activated sludge treatment plants averaged >84% at an average influent concentration of 5.3 ug/L(3). At an industrial aerated lagoon, 67% of an initial N-nitrosodiphenylamine concentration of 3 ug/L was removed(3). N-Nitrosodiphenylamine, added to soil at a concentration of 354 ug/g soil, was degraded 68% by the end of a 30 day incubation at 30 °C in the dark(3). In soil amended with wheat straw (organic matter content increased from 2.16 to 17.5%), N-nitrosodiphenylamine disappeared completely by day 10 of the incubation(4). N-Nitrosodiphenylamine, present at 100 mg/L, reached 0% of its Theoretical BOD in 2 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(5).

The rate constant for the vapor-phase reaction of N-nitrosodiphenylamine with photochemically-produced hydroxyl radicals has been estimated as 2.5X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 16 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). N-Nitrosodiphenylamine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). The maximum adsorption of N-nitrosodiphenylamine, dissolved in methanol, in the UV spectrum was determined to be 262 nm, with limited adsorption reported up to 350 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). N-Nitrosodiphenylamine may photo-degrade in water based on structurally similar nitrosoamines that have degradation half-lives of 12-16 hours(4).

A maximum bioconcentration factor (BCF) of 217 was reported for N-nitrosodiphenylamine in bluegill sunfish (Lepomis macrochirus) exposed to an average N-nitrosodiphenylamine concentration of 9.21 ug/L for 14 days(1). According to a classification scheme(2), this BCF suggests bioconcentration in aquatic organisms is high.

The log Koc of N-nitrosodiphenylamine has been reported as 3.08 (Koc = 1200)(1). According to a classification scheme(2), this Koc value suggests that N-nitrosodiphenylamine is expected to have low mobility in soil(SRC).

The Henry's Law constant for N-nitrosodiphenylamine is estimated as 1.2X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that N-nitrosodiphenylamine is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 43 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 320 days(SRC). N-Nitrosodiphenylamine's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). N-Nitrosodiphenylamine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7X10-5 mm Hg(SRC), determined from a fragment constant method(1).

GROUNDWATER: N-Nitrosodiphenylamine was identified at concentrations of 11.0-17.0 ug/L in aquifer water samples collected from the Iona City Landfill, Iona, MI, during September 1989(1). For samples collected 1981 to 1986, N-nitrosodiphenylamine was detected in 2.4 and 0.6% of the hazardous waste site groundwater samples in EPA regions 3 and 10, respectively; it was not detected in the remaining EPA regions(1-2, 4-9)(2).

DRINKING WATER: N-Nitrosodiphenylamine was detected in 5 of 12 source water samples and 1 of 12 finished water samples collected Nov and Dec 2010 from drinking water treatment plants in China at 0.6-2.9 and 3.3 ng/L, respectively(1).

SURFACE WATER: N-Nitrosodiphenylamine was tested for, but not detected, in tire leachate from Lake Mead, NV water(1). N-Nitrosodiphenylamine was identified, not quantified, in the Great Lakes Basin Ecosystem during 1982(2). N-Nitrosodiphenylamine was detected in samples collected Apr-Sep 2006 from two of seven source waters located in Canada and the US (5 river, 2 lake) and then treated with eleven different disinfection treatments that simulate drinking water processing plants, concentrations were 0.06-0.48 ng/L(3).

N-Nitrosodiphenylamine has been found in raw waste samples and secondary effluent samples from textiles plants in concentrations of 2-20 ug/L. It has also been found in effluents from ink manufacturing facilities(1).

N-Nitrosodiphenylamine was detected at 11 ug/L in wastewater after primary treatment and at <10 ug/L in the final effluent from the Los Angeles Joint Water Pollution Control Plant from samples collected Jul 1978(1). N-Nitrosodiphenylamine was detected in influent water samples collected from Apr to Jun 1981 from the Cedar Creek Wastewater Reclamation-Recharge Facility in Nassau County, NY at 0.8-31.8 ug/L(2). The percent removal of N-nitrosodiphenylamine from the wastewater was >94->99%(2). N-Nitrosodiphenylamine was detected in raw sludge and treated sludge, concentrations unknown, in samples taken from 37 water pollution control plants in Ontario, Canada between January and July 1986(3). N-Nitrosodiphenylamine was detected at 1100 ug/kg in sediment collected from the Iona City Landfill, Iona, MI, during September 1989(4). The concentration of N-nitrosodiphenylamine in soil/waste samples collected from the Doepke Disposal (Holiday, KS) industrial-waste landfill during 1989 was determined to be 2360 ug/kg(5). N-Nitrosodiphenylamine was detected at 0.7-147 ng/g dry weight in 79% of 74 biosolid samples collected Aug 2006 to Mar 2007 from wastewater treatment plants located in 35 US states(6).

SEDIMENT: Sediment cores collected from five sampling stations of the western basin of Lake Ontario were found to contain no traces of N-nitrosodiphenylamine during analysis(1). N-Nitrosodiphenylamine was not detected (detection limit not reported) in sediment samples collected Feb 14-15, 2006 from 18 sampling sites located in Violet Marsh, LA after Hurricane Katrina(2).

N-Nitrosodiphenylamine was monitored for, but not detected, in 9 species of fish collected from 14 locations on Lake Michigan and tributary streams during 1983(1).

In a monitoring study conducted at Love Canal (Niagra Falls, NY) in the summer and fall of 1980, N-nitrosodiphenylamine was detected, not quantified, in sediment, soil, and water samples(1).

Occupational exposure to N-nitrosodiphenylamine may occur through inhalation and dermal contact with this compound at workplaces where N-nitrosodiphenylamine is produced or used(SRC). In 8 industrial rubber plants surveyed, the concentration of N-nitrosodiphenylamine in air was 0.01-1230 ug/cu m with a mean of 37.5 ug/cu m; possible worker exposure was determined to be inhalation and skin(1). Levels as high as 47 ug/cu m N-nitrosodiphenylamine were found in the atmosphere of a factory manufacturing chemicals for tire curing; a sample scraped from a staircase in the factory contained 15000 mg/kg(2).

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

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

Incineration: Pour or sift onto a thick layer of sand and soda ash mixture (90-10). Mix and shovel into a heavy paper box with much paper packing. Burn in an incinerator. Fire may be augmented by adding excelsior and scrap wood. Waste may be dissolved in flammable solvent (alcohols, etc) and sprayed into fire box of an incinerator with afterburner and scrubber.

(1) Nitrosamines may be reduced to the corresponding amine by using nickel-aluminum (Ni-Al) alloy in dilute base. The nitrosamines were completely degraded (99.9%) and only the amines (RR'NH) were found in the final reaction mixtures. No traces (generally <0.1%) of the corresponding, possibly carcinogenic, hydrazines (RR'NNH2) were found in the final reaction mixtures. (2) Nitrosamines may be oxidized by potassium permanganate in 3 M sulfuric acid (KMnO4 in H2SO4). The nitrosamines were completely destroyed (>99.5%). The products of this reaction have not been determined. (3) Nitrosamines may be destroyed by using hydrogen bromide (HBr) in glacial acetic acid. The nitrosamines were completely destroyed (>99%) and the products were presumably the corresponding amines. All of these procedures were validated by an international collaborative study. /Nitrosamines/

For more Disposal Methods (Complete) data for N-Nitrosodiphenylamine (9 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/