HuagongsheHuagongshe Chemistry Print Report · For research reference only
4-Nitro-1,2-phenylenediamine
4-nitrobenzene-1,2-diamine · 4-NITRO-1,2-PHENYLENEDIAMINE · 4-no · 4-n-o-pda · p-nitro-o-phenylenediamine · 4ndb · 4-nop · 4-nopd
Identifiers & Physical Properties
| CAS No. | 99-56-9 |
|---|---|
| Molecular formula | C6H7N3O2 |
| Average molar mass | 153.14 g/mol |
| Monoisotopic mass | 153.05382646 g/mol |
| SMILES | Nc1ccc([N+](=O)[O-])cc1N |
| InChIKey | RAUWPNXIALNKQM-UHFFFAOYSA-N |
| PubChem CID | 5111791 |
| ChEMBL | CHEMBL433721 |
| ChEBI | CHEBI:67116 |
| EC No. | 202-766-3 |
| DTXSID | DTXSID9020958 |
Chemical & Physical Properties
| XLogP | 0.9 |
|---|---|
| Topological polar surface area | 97.9 |
| Hydrogen bond donors | 2 |
| Hydrogen bond acceptors | 4 |
| Rotatable bonds | 0 |
| Heavy atoms | 11 |
| Formal charge | 0 |
| Complexity | 156 |
| Chemical classes | Nitrogen Compounds -> Nitroanilines |
| Cosmetics | Cosmetic ingredients (4-Nitro-o-Phenylenediamine) -> CIR (Cosmetic Ingredient Review)Hair dyeing |
| LogP (partition coefficient) | log Kow = 0.88 |
| Color/Form | Dark red needles from dilute alcohol |
| Solubility | less than 1 mg/mL at 68.9 °F (NTP, 1992)Soluble in acidSparingly sol in watersol in aq soln of hydrochloric acidSolubility in water: poor1 N HCl: ethanol, 1:1: soluble50mg/mL1.2 g/L (20 ºC) |
| Melting point | 390 to 394 °F (NTP, 1992)199.5 °C201 °C199-201 °C (lit.) |
| Vapor pressure | 0.000109 [mmHg] |
| Physical Description | 4-nitro-o-phenylenediamine appears as dark red needles or red solid. (NTP, 1992)Dark red solid[Merck Index] Brown or dark red crystalline powder[MSDSonline]RED POWDER. |
| Dissociation Constants | pKa = 2.61 (conjugate acid) |
| Collision Cross Section | 126.2 Ų [M-H]- [CCS Type: DTBuffer gas: N2Ionization: ESI-Dataset: TOXCASTSource Identifier: DTXSID9020958] |
| Boiling point | 276.04°C (rough estimate) |
| Density | 1.3682 (rough estimate) |
| Refractive index | 1.6910 (estimate) |
| Storage conditions | Keep in dark place,Inert atmosphere,Room temperature |
| Physical state | Powder |
| pKa (acidity coefficient) | 2.06±0.10(Predicted) |
| Color | Brown-red |
| Merck | 14,6622 |
| BRN | 608106 |
| Henry's law constant | 1.3×106 mol/(m3Pa) at 25℃, HSDB (2015) |
| Stability | Stable. Incompatible with strong acids, strong reducing agents, strong oxidizing agents, acid chlorides, acid anhydrides. |
| Cosmetics Ingredients Functions | HAIR DYEING |
| Cosmetic Ingredient Review (CIR) | 4-Nitro-o-phenylenediamine (99-56-9) |
| InChI | 1S/C6H7N3O2/c7-5-2-1-4(9(10)11)3-6(5)8/h1-3H,7-8H2 |
| InChIKey | RAUWPNXIALNKQM-UHFFFAOYSA-N |
| SMILES | Nc1ccc(cc1N)[N+]([O-])=O |
| Toxicology and Carcinogenesis | Bioassay of 4-Nitro-o-phenylenediamine for Possible Carcinogenicity (CASRN 99-56-9) |
| CAS DataBase Reference | 99-56-9(CAS DataBase Reference) |
| EWG's Food Scores | 3-5 |
| FDA UNII | 5A9AX7Y0TT |
| IARC | 3 (Vol. 16, Sup 7) 1987 |
| EPA Substance Registry System | Nitro-o-phenylenediamine (99-56-9) |
| UNSPSC Code | 12352116 |
| NACRES | NA.22 |
| GHS pictogram | GHS07 |
| Signal word | Warning |
| GHS hazard statements | H302-H317 |
| GHS precautionary statements | P280-P301+P312+P330-P302+P352 |
| Personal protective equipment (PPE) | dust mask type N95 (US), Eyeshields, Faceshields, Gloves |
| Hazard symbols | Xn |
| Risk statements (R) | 22-43-68-40-36/37/38-20/21/22 |
| Safety statements (S) | 36/37-45-36-26-22 |
| UN transport number | 2811 |
| Water hazard class (WGK) | 3 |
| RTECS number | ST2975000 |
| TSCA inventory status | TSCA listed |
| Hazard class | 6.1Acute Tox. 4 OralSkin Sens. 1 |
| Packing group | II |
| Customs code | 29215119 |
| Storage class | 11 - Combustible Solids |
| Hazardous substances data | 99-56-9(Hazardous Substances Data) |
| Toxicity | LD50 oral in rat: 681mg/kg |
Safety & Regulations
| GHS classification | WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P270, P272, P280, P301+P317, P302+P352, P321, P330, P333+P317, P362+P364, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 86 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H302: Harmful if swallowed [Warning Acute toxicity, oral] |
|---|---|
| Regulatory information | Chemical: 1,2-Benzenediamine, 4-nitro-4-Nitro-1,2-phenylenediamine: Does not have an individual approval but may be used under an appropriate group standard |
| Other safety information | IMAP assessments - 1,2-Benzenediamine, 4-nitro- and its dihydrochloride salt: Human health tier II assessment |
| DOT label | Poison |
| Fire hazards | Flash point data for this chemical are not availablehowever, it is probably combustible. (NTP, 1992)Combustible. Gives off irritating or toxic fumes (or gases) in a fire. |
| Health hazards | SYMPTOMS: Symptoms of exposure to this compound include irritation of the skin, eyes, mucous membranes and upper respiratory tract, and allergic skin reaction. |
| Hazards summary | May cause skin sensitization[ICSC] A skin, eye, mucous membrane, and respiratory tract irritantHighly toxic by ingestion and inhalation[CAMEO] An irritant[MSDSonline] Search PubMed for name and CAS#: no results |
| Reactive group | Nitro, Nitroso, Nitrate, and Nitrite Compounds, Organic |
| Special Reports | Cosmetic Ingredient Review2-Nitro-p-Phenylenediamine and 4-Nitro-o-Phenylenediamine. JACT 4(3): 161-202, 1985Re-Review: International Journal of Toxicology. 25(S2), 2006. The 1985 safety assessment of 2-nitro-p-phenylenediamine and 4-nitro-o-phenylenediamine was published with the conclusion "for those persons not sensitized, the Expert Panel Concludes that 2-nitro-p-phenylenediamine and 4-nitro-o-phenylenediamine are safe as hair dye ingredients at the current concentration of use" ... Studies available since that safety assessment was completed, along with updated information regarding uses and use concentrations, were considered by the 2006 CIR Expert Panel. The Panel determined to not reopen this safety assessment.DHEW/NCIBioassay of 4-Nitro-o-phenylenediamine for Possible Carcinogenicity (1979) Technical Rpt Series No. 180 DHEW Pub No. (NIH) 79-1736 concludes that under the conditions of this bioassay, dietary administration of 4-nitro-o-phenylenediamine was not carcinogenic in Fischer 344 rats or B6C3F1 mice. |
| TSCA requirements | Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 1-2-Benzenediamine, 4-nitro- is included on this list. |
| Reactivity Profile | 4-NITRO-O-PHENYLENEDIAMINE is incompatible with strong oxidizing agents, strong acids, strong reducing agents, acid chlorides and acid anhydrides. (NTP, 1992) |
| Chemical Dangers | Decomposes on burning. This produces toxic fumes including nitrogen oxides. Reacts with strong acids, strong oxidants and strong reducing agents. |
| Air and Water Reactions | Insoluble in water. |
| Fire fighting | Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)Use water spray, powder. |
| First aid measures | Fresh air, rest.Remove contaminated clothes. Rinse skin with plenty of water or shower.First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.Rinse mouth. |
| First aid | 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. |
| Safe storage | Separated from incompatible materials. See Chemical Dangers. |
| Fire fighting procedures | Water spray, powder. |
| Cleanup methods | Sweep spilled substance into containersif appropriate, moisten first to prevent dusting. |
| Nonfire spill response | 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. |
| Disposal methods | SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. 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 qualitypotential migration in soil or watereffects on animal, aquatic, and plant lifeand conformance with environmental and public health regulations. |
| Spillage disposal | Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. |
| Preventive Measures | PREVENT DISPERSION OF DUST! STRICT HYGIENE! Do not eat, drink, or smoke during work. |
| Isolation and Evacuation | Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]: |
| Eye Prevention | Wear safety goggles. |
| Interactions | The antimutagenic activity of celecoxib was determined using histidine mutant Salmonella typhimurium strains TA98, TA100, TA102 and TA1535 against directly acting mutagens /including / 4-nitro-o-phenylenediamine (NPDA) ...and mutagens needing activation ... . Celecoxib inhibited ... NPDA-induced mutations of TA100. ... At concentrations of 0.2 mg/plate, celecoxib significantly inhibited NPDA-...induced mutations of TA98 by 52.5 ...%, ... (P < 0.001 ... ). ...... Antimutagenicity of the 3-hydroxy-3-methylgutaryl-CoA (HMG-CoA) reductase inhibitors atorvastatin and lovastatin was studied using the Ames Salmonella typhimurium assay. Directly acting mutagens, sodium azide (NaN(3)) and 4-nitro-o-phenylenediamine (NPDA), were used to induce mutation in Salmonella strains TA98 and TA100. The antimutagenicity of lovastatin and atorvastatin was found to be significant (p < 0.01) and dose-dependent. The percentage inhibition of a 3 mg lovastatin-treated plate was found to be 79.9% and 61.8% against NPDA- and NaN(3)-induced mutation to TA98 and TA100, respectively. Atorvastatin (0.5 mg/plate) inhibited NPDA-and NaN(3)-induced mutation to TA98 and TA100 by 78.6% and 45.5%, respectively. Atorvastatin showed antimutagenic activity at lower concentrations than lovatstatin. ...... honeybee (Apis mellifera) venom, ... collected in the State of São Paulo, Brazil, ... acted against the mutagenicity of 4-nitro-o-phenylenediamine /in Salmonella typhimurium TA98/ ...Water, acetone and chloroform extracts of Emblica officinalis Gaertn. (Indian gooseberry)fruit reduced sodium azide and 4-nitro-o-phenylenediamine induced his+ revertants significantly in TA100 and TA97 a strains respectively of S. typhimurium. The chloroform extract was less active as compared to water and acetone extracts. Autoclaving of water extract for 15 min did not reduce its activity. ...For more Interactions (Complete) data for 4-NITRO-1,2-DIAMINOBENZENE (9 total), please visit the HSDB record page. |
| Ecotoxicity values | LC50Species: Tetrahymena pyriformis (Ciliate)Conditions: freshwater, static, 28 °CConcentration: 46000 ug/L for 60 hr (95% confidence interval: 20650-67820 ug/L)Effect: population change |
| Environmental fate | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 72(SRC), determined from a log Kow of 0.88(2) and a regression-derived equation(3), indicates that 4-nitro-1,2-diaminobenzene is expected to have high mobility in soil(SRC). However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(4), suggesting that mobility may be much lower in some soils(SRC). Volatilization of 4-nitro-1,2-diaminobenzene from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.4X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(5). 4-Nitro-1,2-diaminobenzene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-4 mm Hg(SRC), determined from a fragment constant method(6). Information is not available regarding the biodegradation potential of 4-nitro-1,2-diaminobenzenehowever, 33% percent of structurally-related o-phenylenediamine was removed over 120 hours based on chemical oxygen demand measurements and using an activated sludge inoculum(7).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 72(SRC), determined from a log Kow of 0.88(2) and a regression-derived equation(3), indicates that 4-nitro-1,2-diaminobenzene is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.4X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Information is not available regarding the biodegradation potential of 4-nitro-1,2-diaminobenzeneATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-nitro-1,2-diaminobenzene, which has an estimated vapor pressure of 1.1X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 4-nitro-1,2-diaminobenzene 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 17 hours(SRC), calculated from its rate constant of 2.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 4-nitro-1,2-diaminobenzene may be removed from the air by wet or dry deposition(SRC). 4-Nitro-1,2-diaminobenzene absorbs light at wavelengths above 290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC). |
| Adverse effects | Skin Sensitizer - An agent that can induce an allergic reaction in the skin. |
| Toxicity summary | Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.org |
| Ecotoxicity excerpts | /OTHER TERRESTRIAL SPECIES/ ... The toxicity of 10 benzamines was tested by the well diffusion assay technique against 18 common bacterial species including the nitrogen-fixing bacterium Azotobacter vinelandii. p-Phenylenediamine was found to be inhibitory to the growth of Aeromonas hydrophila and Pseudomonas fluorescens. o-Phenylenediamine was inhibitory to Escherichia coli, Klebsiella pnemoniae, Salmonella enteritidis, and Shigella sonnei. 2,5-Diaminotoluene was inhibitory to the growth of P. fluorescens and Streptococcus mitis. The growth of A. vinelandii was inhibited by p-phenylenediamine and 2,5-diaminotoluene in the well diffusion assay. p-Nitroaniline was also found to be inhibitory to the growth of A. vinelandii in Burk's nitrogen-free medium. The nitrogenase activity of A. vinelandii was inhibited by p-phenylenediamine, 2,5-diaminotoluene, p-nitroaniline, 2-nitro-p-phenylenediamine, 3-nitro-o-phenylenediamine, and 4-nitro-o-phenylenediamine. ... |
| Ongoing Test Status | 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. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=99-56-9] |
| ICSC Environmental Data | Environmental effects from the substance have not been investigated adequately. |
| Medical Surveillance | Routine checking of lips, tongue and nail beds of exposed personnel for signs of cyanosis. /Protect/ from exposure those individuals with anemia, cardiovascular or pulmonary diseases. |
| Soil Adsorption/Mobility | The Koc of 4-nitro-1,2-diaminobenzene is estimated as 72(SRC), using a log Kow of 0.88(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that 4-nitro-1,2-diaminobenzene is expected to have high mobility in soil. However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(4), suggesting that mobility may be much lower in some soils(SRC). |
| TSCA Test Submissions | The teratogenicity of 2-amino-4-nitroaniline (ANA) was evaluated in pregnant outbred albino CD-1 mice (118/group, 11-47/treated group) exposed to ANA by subcutaneous injection at dose levels of 0, 16, 32, 64, 128, 256, 512, 768 or 1024 mg/kg/day on gestation days (GD) 6-15. The mice were sacrificed on GD 18. Significant dose-related differences between treated and control animals were observed in the following: decreased weight gain of dams during pregnancy and average fetal weight (256 mg/kg/day and above dose levels), decreased average number of live fetuses/dam (768 mg/kg/day level), increased mortality (6 of 36 and 7 of 37 at dose levels of 768 and 1024 mg/kg/day, respectively, versus no treatment related mortalities in lower dose levels or in controls), increased average percentage malformed fetuses (256 mg/kg/day and above), increased cleft palate (the major malformation overall, significant by Fisher's Exact Test (FE Test) for doses of 256 mg/kg/day and above), malformed and missing major blood vessels, including missing subclavian artery and aortic arch (512 and 1024 mg/kg/day levels), and increased incidence of white lesions in the left ventricle of the fetal heart which tested positive for calcium (512 mg/kg/day and above). |
| Natural Pollution Sources | 4-Nitro-1,2-diaminobenzene is not known to occur as a natural product. |
| Personal protective equipment (PPE) | dust mask type N95 (US), Eyeshields, Faceshields, Gloves |
| Water hazard class (WGK) | 3 |
| TSCA inventory status | TSCA listed |
| RTECS number | ST2975000 |
| UN transport number | 2811 |
| Customs code | 29215119 |
| Toxicity | LD50 oral in rat: 681mg/kg |
| Risk statements (R) | 22-43-68-40-36/37/38-20/21/22 |
| Signal word | Warning |
| GHS pictogram | GHS07 |
| Hazard symbols | Xn |
| Safety statements (S) | 36/37-45-36-26-22 |
| Hazard class | 6.1Acute Tox. 4 OralSkin Sens. 1 |
| Storage class | 11 - Combustible Solids |
| Packing group | II |
| GHS hazard statements | H302-H317 |
| GHS precautionary statements | P280-P301+P312+P330-P302+P352 |
| Hazardous substances data | 99-56-9(Hazardous Substances Data) |
Applications & Uses
Uses
4-Nitro-o-phenylenediamine was used to study the in vitro activation of 4-nitro-o-phenylenediamine into a potent mutagen in Salmonella typhimurium strain TA98 .
General Description
4-nitro-o-phenylenediamine appears as dark red needles or red solid.
Preparation & Synthesis
Preparation
Prepared by reduction of 2,4-dinitroaniline using H2S in ammonia water.