4-Amino-diphenylamin

Cosmetics ingredient -> Colorant

Cosmetic ingredients (N-Phenyl-p-Phenylenediamine) -> CIR (Cosmetic Ingredient Review)

Hair dyeing

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

1.1 at 100 °C

1.09 g/cm³

Needles (alcohol)

Purple powder

Purple needles

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

Slightly soluble in water, chloroform; very soluble in ethanol; soluble in diethyl ether, ligroin

Soluble in alcohol and acetone

Insoluble in water; soluble in oxygenated solvents

Solubility: 500 mg/L at 20 °C and pH 8.9

Solubility in water, g/100ml at 20 °C: 0.05

380 °F (NTP, 1992)

380 °F'

193 °C

669 °F at 760 mmHg (NTP, 1992)

354 °C

354 °C

163 to 167 °F (NTP, 1992)

75 °C

75 °C

0.0000121 [mmHg]

1.21X10-5 mm Hg at 25 °C (extrapolated)

Vapor pressure, Pa at 20 °C: 0.000076

Warning

H302 (97.2%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P272, P273, P280, P301+P317, P302+P352, P305+P351+P338, P321, P330, P333+P317, P337+P317, P362+P364, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 680 reports by companies from 21 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

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

Chemical: 1,4-Benzenediamine, N-phenyl-

1,4-Benzenediamine, N1-phenyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 1,4-Benzenediamine, N1-phenyl- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 10-05-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/14731

4-Aminodiphenylamine: Does not have an individual approval but may be used under an appropriate group standard

This chemical is combustible. (NTP, 1992)

Combustible.

SYMPTOMS: Symptoms of exposure to this compound may include irritation of the eyes and upper respiratory tract. It may also cause irritation of the skin and mucous membranes. Other symptoms include headache, dizziness and methemoglobinemia with symptoms of cyanosis including bluish discoloration of the lips, earlobes and fingernails. Dermatitis has been reported.

Potential adverse effects form using this hair dye include dermatitis, eye injury, and liver damage. [HSDB] When it was used in hair dyes, sensitization was relatively low in hairdressers; [Kanerva, p. 1749] A skin and eye irritant; May cause skin sensitization; Can induce methemoglobinemia if ingested; [ICSC] Skin designation; Danger of skin sensitization; 3B carcinogen; [MAK]

Bioassay of p-Aminodiphenylamine for Possible Carcinogenicity (1978) Technical Rpt Series No. 82 DHEW Pub No. (NIH) 78-1332, U.S. Department of Health Education and Welfare, National Cancer Institute, Bethesda, MD 20014[Available from, as of April 4, 2003: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr082.pdf]

European Commission, ESIS; IUCLID Dataset, p-aminodiphenylamine (101-54-2) (2000 CD-ROM edition).[Available from, as of March 1, 2009: http://esis.jrc.ec.europa.eu/]

Acute Tox. 4 (97.2%)

Acute toxicity - category 4

Acute toxicity (Oral) - Category 4

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

Use dry powder, carbon dioxide.

Fresh air, rest. Refer for medical attention.

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. Give one or two glasses of water to drink. Do NOT induce vomiting. 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.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol 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.

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 quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

EC50; Species: Daphnia magna (Water flea, age <24 hr); Conditions: freshwater, static, pH 7.8-8.1, dissolved oxygen 96-99% saturated; Concentration: 1220 ug/L for 24 hr (95% confidence interval: 520-2920 ug/L); Effect: intoxication, immobilization /98% purity/

EC50; Species: Daphnia magna (Water flea, age <24 hr); Conditions: freshwater, renewal, pH 7.8-8.1, dissolved oxygen 96-99% saturated; Concentration: 370 ug/L for 48 hr; Effect: intoxication, immobilization /98% purity/

EC50; Species: Daphnia magna (Water flea); Conditions: static not aerated, 20.4 °C, pH 7.9 + or -0.1, dissolved oxygen 8.3-8.9 mg/L; Concentration: 4.1 mg/L for 24 hr; Effect: immobilization /98.8% purity/

EC50; Species: Daphnia magna (Water flea); Conditions: static unaerated, 19.8-21.5 °C, pH 7.5-9.7, dissolved oxygen 8.4-14.4 mg/L; Concentration: 0.1 mg/L for 21 days; Effect: reproduction rate /98.8% purity/

For more Ecotoxicity Values (Complete) data for P-AMINODIPHENYLAMINE (7 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3.1X10+3(SRC), determined from a structure estimation method(2), indicates that p-aminodiphenylamine is expected to have slight mobility in soil(SRC). The pKa of p-aminodiphenylamine is 5.20(3), indicating that this compound will partially exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of p-aminodiphenylamine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.7X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(5). p-Aminodiphenylamine is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.21X10-5 mm Hg at 25 °C(6). Reported inherent biodegradation values of 28% after 20 days in an adapted activated sludge and 58% after 3 hours in a mixed, non-adapted activated sludge inoculum(7) suggest that biodegradation in the aquatic environment may be an important fate process(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3.1X10+3(SRC), determined from a structure estimation method(2), indicates that p-aminodiphenylamine 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 3.7X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). A pKa of 5.20(5) indicates p-aminodiphenylamine will exist partially in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(6). According to a classification scheme(7), an estimated BCF of 5.1(SRC), from an estimated log Kow of 1.82(8) and a regression-derived equation(9), suggests the potential for bioconcentration in aquatic organisms is low. Reported inherent biodegradation values of 28% after 20 days in an adapted activated sludge and 58% after 3 hours in a mixed, non-adapted activated sludge inoculum(10) suggest that biodegradation in the aquatic environment may be an important fate process(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), p-aminodiphenylamine, which has a vapor pressure of 1.21X10-5 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase p-aminodiphenylamine 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 1.9 hours(SRC), calculated from its rate constant of 2.0X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase p-aminodiphenylamine may be removed from the air by wet or dry deposition(SRC). p-Aminodiphenylamine contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).

On the basis of the data included in this report, the CIR Expert Panel concludes that N-Phenyl-p-Phenylenediamine... safe for use in hair dyes at concentrations up to 1.7% (as the free base).

Safe for use in cosmetics, with qualifications

Redness. Pain.

Redness. Pain.

Blue lips, fingernails and skin. Confusion. Convulsions. Dizziness. Headache. Nausea. Abdominal pain. Vomiting. Unconsciousness.

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: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=101-54-2]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of p-aminodiphenylamine can be estimated to be 3.1X10+3(SRC). According to a classification scheme(2), this estimated Koc value suggests that p-aminodiphenylamine is expected to have slight mobility in soil. The pKa of p-aminodiphenylamine is 5.20(3), indicating that this compound will partially exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/HUMAN EXPOSURE STUDIES/ A study of contact dermatitis in Italian hairdressers was conducted in a cohort of 302 hairdressers (43 men and 259 women, mean age 24.6 years) who were treated for skin problems at Italian dermatology clinics over a 5 year period. Of these, 184 were patch tested with an Italian standard allergen series and a hairdresser's allergen series. ... The subjects had been employed as hairdressers a mean of 5.3 years. ... Among hair dye allergens, p-phenylenediamine, para-aminodiphenylamine, o-nitro-p-phenylenediamine, and para-toluenediamine caused a high incidence of positive reactions, 24.2, 10.6, 7.9, and 13.2%, respectively. ... It was concluded that a high proportion of hairdressers who seek treatment for skin problems have allergic contact dermatitis.

/HUMAN EXPOSURE STUDIES/ A cleaner at a chemical plant suffering from allergic skin reaction of the face, neck and arms was tested. Positive reaction to 0 25% test substance in petrolatum after 48 and 72 hr.

/HUMAN EXPOSURE STUDIES/ Cosmetic intolerance has been studied in 5202 patients; tested for possible contact dermatitis. Results: 107 (2.1%) showed positive reaction to the test substance; from 156 patients with pure allergy to cosmetics 5 (3.2%) -reacted positve to the test substance.

/HUMAN EXPOSURE STUDIES/ Tests were performed in 181 persons with confirmed group sensitization to aromatic amino compounds; test concentration 1% of the test substance; results: 96 patients (53%) showed positive reaction.

For more Human Toxicity Excerpts (Complete) data for P-AMINODIPHENYLAMINE (8 total), please visit the HSDB record page.

AEROBIC: p-Aminodiphenylamine, present at 2.4 mg/L biodegraded 0, 24, and 28% in 5, 10, and 20 days, respectively, using an adapted activated sludge inoculum in a DEV test(1). p-Aminodiphenylamine, present at 100 mg DOC/L, reached 58% DOC after 3 hours using a mixed, non-adapted activated sludge inoculum in a Zahn-Wellens test(1).

Aminodiphenylamine binds to the proteins of the intestinal mucosa.

Skin segments (1 sq cm) of male albino rats without underlying connective tissue and subcutaneous fat were used for uptake and efflux studies. 4-ADPA binds to skin showing saturation kinetics with Km= 2.54 X10 (-4) and Vmax= 4.76 micromol/g skin. Uptake dependent upon area of skin, concentration, exposure time, temperature and pH of the vehicle. No effects of bioinhibitors, suggesting a non-energy dependent process. Skin bound to 4-ADPA was effluxed through serum proteins.

P-aminodiphenylamine (p-ADPA) binds liver proteins. Aspartic and glutamic acids are presumably the responsible units in the protein chain involved in this binding with p-ADPA. p-ADPA is changed into a quinone structure after atmospheric oxidation in Krebs-ringer-bicarbonate buffer, pH 7.4, in the presence of trace metal ions. This oxidized form of p-ADPA binds with aspartic acid at pH 7.4 and temp 40 deg in 2 hr.

CIR ingredient: N-Phenyl-p-Phenylenediamine

Used to produce dyes, pharmaceuticals, and photographic chemicals; [HSDB] Formerly used as a hair dye; [Kanerva, p. 1749]

Dressing Hair [Category: Other]

Dye intermediate, pharmaceuticals, photographic chemicals.

Azoic dye, diazo component

Oxidation dye color in hair dyes

2023: 10,000,000 - <50,000,000 lb

1,4-Benzenediamine, N-phenyl- is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#3904]

Reduction of the coupling product of diazotized sulfanilic acid and diphenylamine

Aniline + p-chloronitrobenzene (amine formation/nitro reduction)

By heating aniline with p-chloronitrobenzene in the presence of a copper salt and catalytically hydrogenating the nitro group.

Cosmetics product ingredient: p-Aminodiphenylamine

Information on 5 consumer products that contain N-Phenyl-p-phenylenediamine in the following categories is provided:

All Other Basic Organic Chemical Manufacturing

1,4-Benzenediamine, N1-phenyl-: ACTIVE