4-Methoxy-1,3-benzoldiamin

Nitrogen Compounds -> Amines, Aromatic

Carcinogens

Needles from ether

Colorless solid (needles).

Soluble in alcohol, hot ether; slightly soluble in DMSO

Solubility in water: miscible

153 °F (NIOSH, 2024)

67-68 °C

68 °C

153 °F

2,4-diaminoanisole appears as colorless needles. Primarily used (along with salts such as 2,4-diaminoanisole sulfate) as a component of hair & fur dye formulations. (NIOSH, 2024)

Colorless solid (needles). [Note: The primary use (including its salts such as 2,4-diaminoanisole sulfate) is a component of hair & fur dye formulations.] [NIOSH]

COLOURLESS SOLID IN VARIOUS FORMS.

Colorless solid (needles). [Note: The primary use (including its salts such as 2,4-diaminoanisole sulfate) is a component of hair & fur dye formulations.]

Danger

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

P203, P264, P270, P273, P280, P301+P317, P318, P330, P391, P405, and P501 (click each P-code to see the statement)

Danger

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P273, P280, P301+P317, P318, P330, P391, P405, and P501 (click each P-code to see the statement)

Chemical: 1,3-Benzenediamine, 4-methoxy-

Hazard Traits - Carcinogenicity

1,3-Benzenediamine, 4-methoxy-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:

Combustible.

Coal tar hair dyes posing a risk of cancer. (a) The principal display panel of the label and any labeling accompanying a coal tar hair dye containing any ingredient listed in paragraph (b) of this section shall bear, in accordance with the requirements of §740.2, the following: Warning-Contains an ingredient that can penetrate your skin and has been determined to cause cancer in laboratory animals. (b) Hair dyes containing any of the following ingredients shall comply with the requirements of this section: (1) 4-methoxy-m-phenylenediamine (2,4-diaminoanisole) and (2) 4-methoxy-m-phenylenediamine sulfate (2,4-diaminoanisole sulfate).

FISHBEIN L; A SURVEY OF TECHNIQUES FOR ESTIMATING AND MONITORING AROMATIC AMINES OF MAJOR INDUSTRIAL IMPORTANCE; IARC SCI PUBL 4(40) P75 (1981). REVIEW OF TECHNIQUES FOR ESTIMATION AND MONITORING OF AROMATIC AMINES INCLUDING 2,4-DIAMINOANISOLE.

DHHS/NIOSH; Current Intelligence Bulletins: 2,4-Diaminoanisole (1986) DHHS (NIOSH) Pub No. 86-124

Bioassay of 2,4-Diaminoanisole sulfate for Possible Carcinogenicity (1978) Technical Rpt Series No. 84 DHEW Pub No. (NIH) 78-1334, U.S. Department of Health Education and Welfare, National Cancer Institute, Bethesda, MD 20014

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:

Use water spray, powder, foam, carbon dioxide.

Fresh air, rest.

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 .

Excerpt from NIOSH Pocket Guide for 2,4-Diaminoanisole (and its salts):

(General first aid procedures)

Separated from strong oxidants Well closed.

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/

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/

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

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/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for 2,4-DIAMINOANISOLE (6 total), please visit the HSDB record page.

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 addnl 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 synth & 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/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for 2,4-DIAMINOANISOLE (13 total), please visit the HSDB record page.

The mutagenicity of aromatic amines, as measured by the Salmonella/microsome assay, was inactivated by ozone treatment.

Phenobarbital (75 mg/kg ip at 72, 48, and 24 hr previously) pretreatment of rats reduced the LD50 of 2,4-diaminoanisole from 116 to 97 mg/kg, and increased the initial rate of urinary excretion.

8 Kinds of o- and m-phenylenediamine (PD) derivatives, which are used as oxidative-type hair dyes, were treated with hydrogen peroxide (H2O2). Both before and after H2O2 treatment, their mutagenicity was tested by using Salmonella typhimurium TA98 in the presence or absence of a mammalian metabolic activation system (S9 mix). After H2O2 treatment, the mutagenic potencies of p-nitro-o-phenylenediamine, 3,4-diaminotoluene, p-nitro-m-phenylenediamine and 2,4-diaminophenol did not vary or slightly increased in comparison with those of the starting materials. The mutagenicity of o-PD, p-chloro-o-phenylenediamine (p-Cl-o-PD), m-PD and 2,4-diaminoanisole (p-OMe-m-PD) was enhanced remarkably by treatment with H2O2 and all the oxidation products required metabolic activation by S9 mix for their mutagenesis.

The effect of the carcinogenic hair dye component 2,4-diaminoanisole (2,4-DAA) on thyroid and pituitary morphology was studied. Heavy pigmentation of the hypertrophied thyroid epithelium was present when the animals were fed with 2,4-DAA for 6 weeks. Another hair dye component m-phenylenediamine (m-PDA), which lacks the methoxy group, and which is not carcinogenic, prevented the dark pigmentation of the thyroid epithelium caused by 2,4-DAA, but had only a slight effect on the hypertrophy of the gland. In the pituitary gland of 2,4-DAA-fed animals only a few aldehyde fuchsin positive thyrotrope cells were present. When 2,4-DAA and m-PDA were fed simultaneously, the number of hypertrophied chromophobic cells was greatly increased and the aldehyde fuchsin-positive cells were practically absent.

For more Interactions (Complete) data for 2,4-DIAMINOANISOLE (6 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 53(SRC), determined from a structure estimation method(2), indicates that 2,4-diaminoanisole is expected to have high mobility in soil(SRC). 2,4-Diaminoanisole is a weak base with an estimated pKa of 5.15(SRC), calculated by a method based on linear free energy relationships and perturbed molecular orbital theory(3). This estimated pKa indicates that 2,4-diaminoanisole will partially exist in the protonated form in acidic moist soils and cations generally adsorb to soils stronger than neutral molecules(4). Moreover, anilines (aromatic amines) are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(5,6), suggesting that the mobility of 2,4-diaminoanisole may be much lower in some soils than indicated by the estimated Koc value(SRC). Volatilization of 2,4-diaminoanisole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.2X10-10 atm-cu m/mole for the neutral species(SRC), using a fragment constant estimation method(7) and since cations will not volatilize. 2,4-Diaminoanisole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.047 mm Hg(SRC), determined from a fragment constant method(8). Biodegradation data were not available(SRC, 2006).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 53(SRC), determined from a structure estimation method(2), indicates that 2,4-diaminoanisole is not expected to adsorb to suspended solids and sediment(SRC). 2,4-Diaminoanisole is a weak base with an estimated pKa of 5.15(SRC), calculated by a method based on linear free energy relationships and perturbed molecular orbital theory(3). This estimated pKa indicates that 2,4-diaminoanisole will partially exist in the protonated form and cations generally adsorb to suspended solids and sediment stronger than neutral molecules(4). Volatilization from water surfaces is not expected(5) based upon an estimated Henry's Law constant for the neutral species of 7.2X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(6) and the fact that cations will not volatilize. According to a classification scheme(7), BCF values of 1.3 to 4.6 measured in fish(8), suggest bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2006).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2,4-diaminoanisole, which has an estimated vapor pressure of 0.047 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 2,4-diaminoanisole 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 2 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).

The substance can be absorbed into the body through the skin and by ingestion.

inhalation, skin absorption, ingestion, skin and/or eye contact

On the basis of the information included in this report the CIR Expert Panel concludes that 4-Methoxy-m-Phenylenediamine, 4-Methoxy-m-Phenylenediamine Sulfate and 4-Methoxy-m-Phenylenediamine HCL are unsafe for use in cosmetic products.

The ingredient is unsafe for use in cosmetics

MAY BE ABSORBED!

In Animals: irritation skin; thyroid, liver changes; teratogenic effects; [potential occupational carcinogen]

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/

Using a structure estimation method based on molecular connectivity indices(1), the Koc for 2,4-diaminoanisole can be estimated to be 53(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2,4-diaminoanisole is expected to have high mobility in soil. 2,4-Diaminoanisole is a weak base with an estimated pKa of 5.15(SRC), calculated by a method based on linear free energy relationships and perturbed molecular orbital theory(3). This estimated pKa indicates that 2,4-diaminoanisole will partially exist in the protonated form in acidic moist soils and cations generally adsorb to soils more strongly than their neutral counterparts(4). Moreover, anilines (aromatic amines) are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(5,6), suggesting that the mobility of 2,4-diaminoanisole may be much lower in some soils than indicated by the estimated Koc value(SRC).

/OTHER TOXICITY INFORMATION/ ... Carcinogenicity in man ... not been established.

/OTHER TOXICITY INFORMATION/ Ingredients found unsafe for use in cosmetics: Ingredient: 4-methoxy-m-phenylenediamine; Safety Concern: carcinogenicity. /From table/

2,4-Diaminoanisole's former production and use in the preparation of dyes, as an intermediate in the production of C.I. Brown 2, and as a corrosion inhibitor in steel(1) may have resulted in its release to the environment through various waste streams(SRC).

Coal tar hair dyes posing a risk of cancer. (a) The principal display panel of the label and any labeling accompanying a coal tar hair dye containing any ingredient listed in paragraph (b) of this section shall bear, in accordance with the requirements of §740.2, the following: Warning-Contains an ingredient that can penetrate your skin and has been determined to cause cancer in laboratory animals. (b) Hair dyes containing any of the following ingredients shall comply with the requirements of this section: (1) 4-methoxy-m-phenylenediamine (2,4-diaminoanisole) and (2) 4-methoxy-m-phenylenediamine sulfate (2,4-diaminoanisole sulfate).

To clarify the mechanism of carcinogenesis by hair dyes ... /the authors/ compared the extent of DNA damage induced by mutagenic m-phenylenediamine and 4-methoxy-m-phenylenediamine, using (32)P-5'-end-labeled DNA fragments obtained from the human c-Ha-ras-1 protooncogene and the p53 tumor suppressor gene. Carcinogenic 4-methoxy-m-phenylenediamine caused DNA damage at thymine and cytosine residues in the presence of Cu(II). Catalase and bathocuproine, a Cu(I)-specific chelator, inhibited 4-methoxy-m-phenylenediamine-induced DNA damage, suggesting the involvement of H2O2 and Cu(I). Superoxide dismutase (SOD) enhanced the DNA damage. Formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) was induced by 4-methoxy-m-phenylenediamine in the presence of Cu(II). UV-visible spectroscopic studies have shown that Cu(II) mediated autoxidation of 4-methoxy-m-phenylenediamine and SOD accelerated the autoxidation. On the other hand, non-carcinogenic m-phenylenediamine did not cause clear DNA damage and significant autoxidation even in the presence of Cu(II). These results suggest that carcinogenicity of m-phenylenediamines is associated with ability to cause oxidative DNA damage ...

Following ip administration of 50 mg/kg bw (14)C-labelled 2,4-diaminoanisole to rats... . Major metabolites were 4-acetylamino-2-aminoanisole, 2,4-diacetylaminoanisole, 2,4-diacetylaminophenol, 5-hydroxy-2,4-diacetylaminoanisole and 2-methoxy-5-(glycolamido)acetanilide or its isomer. These metabolites were excreted in urine both free and as glucuronides and sulfates.

Following ip administration of 50 mg/kg bw (14)C-labelled 2,4-diaminoanisole to rats, 85% of radioactivity was excreted in urine and 9% in feces after 48 hr.

Injection of (3)H-2,4-diaminoanisole (10-200 mg/kg) into rats led to irreversible binding of liver and kidney proteins. Irreversibly bound material was preferentially localized in the microsomal fraction. Non-bound (3)H-2,4-diaminoanisole was rapidly cleared from plasma, liver and kidneys, whereas considerable amounts irreversibly bound could still be demonstrated 24 hr after a dose of 100 mg/kg ip.

Scalp penetration of 2,4-diaminoanisole (DAA) that occurs under conditions of hair dye usage was evaluated for both rhesus monkey and man using (14)C-labeled material. Average dose excretion of DAA in rhesus monkey was 0.02% and in man 0.015%.

No fixation of 2,4-diaminoanisole which passes through the cutaneous barrier is found in either liver or thyroid of hairless rats, 4 days after topical application.

For more Absorption, Distribution and Excretion (Complete) data for 2,4-DIAMINOANISOLE (7 total), please visit the HSDB record page.

CIR ingredient: 4-Methoxy-m-Phenylenediamine

An oxidizing agent used in hair dyes (former use) and fur dyes; [HSDB]

Was used extensively in permanent hair dyes until the late 1970s; [IARC]

Fur Dressing and Dyeing [Category: Industry]

Preparation of dyes, especially hair and fur dyes; intermediates in the production of C.I. Basic Brown 2; as corrosion inhibitor for steel /Former use/

Former Use: ...Used extensively in permanent, oxidative hair dyes until the late 1970s. /2,4-Diaminoanisole and its sulfate salt/

(1977) 4.70X10+6 G (PRINCPL CUSTMS DISTS)

(1979) 8.80X10+6 G (PRICNPL CUSTMS DISTS)

(1978) 1.36X10+7 G (EST CONSUMPTION)

(1986) 10 thousand-500 thousand pounds

In January 1978, NIOSH reported that approx 75% of the then current oxidation (permanent) hair-dyes formulations contained 2,4-diaminoanisole at levels of 0.05-2.0%, depending on the shade. Formulations for producing brown & blonde shades have been reported to contain significantly less 2,4-diaminoanisole than those for black shades.

1,3-Benzenediamine, 4-methoxy-: ACTIVE

2,4-diaminoanisole ... believed to be used as an intermediate in the manufacture of one commercially significant dye, CI basic brown 2. ... CI basic brown 2 was reported to be used mainly in dyeing acrylic fibers, although it was also present in variety of other products, including shoe polishes. 2,4-diaminoanisole and its sulfate may serve as oxidation bases in dyeing of furs.