2,5-디아미노톨루엔황산염

Nitrogen Compounds -> Amines, Aromatic

Nitrogen Compounds -> Amines, Aromatic

Cosmetic ingredients (Toluene-2,5-Diamine Sulfate) -> CIR (Cosmetic Ingredient Review)

Hair dyeing

Grey to white powder

Off-white powder

less than 1 mg/mL at 68 °F (NTP, 1992)

In water, 5.03 g/L at 20 °C

Soluble in water and ethanol

In acetone/water 1:1 <1 g/L; in dimethylsulfoxide: 5 to 15 g/L; in ethanol: 1 to 10 g/L

Solubility in water: good

2,5-toluenediamine sulfate is a light tan to light purple powder. (NTP, 1992)

Off-white solid; [HSDB] Light tan to light purple solid; [CAMEO]

Grey to white solid; [ICSC] Light brown powder; [Sigma-Aldrich MSDS]

GREY-TO-WHITE POWDER.

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

P261, P264, P270, P271, P272, P273, P280, P301+P316, P302+P352, P304+P340, P317, P321, P330, P333+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

P261, P264, P270, P271, P272, P273, P280, P301+P316, P302+P352, P304+P340, P317, P321, P330, P333+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

Chemical: 1,4-Benzenediamine, 2-methyl-, sulfate (1:1)

Chemical: 1,4-Benzenediamine, 2-methyl-, sulfate

REACH registered substance: 2-methyl-p-phenylenediamine sulfate (EC: 210-431-8)

Toluene-2,5-diamine sulphate: Does not have an individual approval but may be used under an appropriate group standard

1,4-Benzenediamine, 2-methyl-, sulfate: 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.

IMAP assessments - 1,4-Benzenediamine, 2-methyl-, sulfate: Human health tier II assessment

IMAP assessments - 1,4-Benzenediamine, 2-methyl-, sulfate: Human health tier II assessment

Flash point data for this chemical are not available. It is probably combustible. (NTP, 1992)

Combustible. Gives off irritating or toxic fumes (or gases) in a fire.

No evidence of carcinogenicity or teratogenicity in mice or rats; Some evidence of mutagenicity; Emergency treatment: Paraphenylenediamine; [HSDB] May cause skin sensitization; [eChemPortal: ESIS] See 2,5-Diaminotoluene.

A mild skin and eye irritant; May cause skin sensitization; Can be absorbed through skin; [ICSC] A potent skin sensitizer, with positive patch test results observed in hairdressers with dermatitis; In 14-day feeding studies of rats, causes increased AST, CPK, LDH, and ALT at 60 mg/kg/day; [EC - SCCS] May cause irritation; Toxic by ingestion; [Sigma-Aldrich MSDS] See 2,5-Diaminotoluene.

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. 1,4-Benzenediamine, 2-methyl-, sulfate is included on this list. Effective date: 4/29/83; Sunset date: 4/29/93.

Acidic organic/inorganic salts, such as 2,5-TOLUENEDIAMINE SULFATE, are generally soluble in water. The resulting solutions contain moderate concentrations of hydrogen ions and have pH's of less than 7.0. They react as acids to neutralize bases. These neutralizations generate heat, but less or far less than is generated by neutralization of inorganic acids, inorganic oxoacids, and carboxylic acid. They usually do not react as either oxidizing agents or reducing agents but such behavior is not impossible. Many of these compounds catalyze organic reactions.

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

Use water spray, foam, dry powder, 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. Give a slurry of activated charcoal in water to drink. Induce vomiting (ONLY IN CONSCIOUS PERSONS!). 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: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then dampen the solid spill material with toluene, then transfer the dampened material to a suitable container. Use absorbent paper dampened with toluene to pick up any remaining material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent-wash all contaminated surfaces with toluene 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 harm/injury/toxicity 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 and plant life; and conformance with environmental and public health regulations.

Selected as the 2025 American Contact Dermatitis Society Allergen of the Year. It disproportionately affects hairdressers and frequent users of hair dye.

A 2025 publication notes that toluene-2,5-diamine sulfate is often omitted from standard patch test screening series and thus is possibly underdiagnosed.

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

On the basis of the data presented in this report the CIR Expert Panel concludes that toluene-2,5-diamine and toluene-2,5-diamine sulfate are safe as hair dye ingredients in the present practices of use and concentration as described in this safety assessment, but the availaale data are insufficient to support the safety of toluene-3,4 diamine as a hair dye ingredient

Safe for use in cosmetics, with qualifications

/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. ... 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. ... 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. Because many of these organisms are common soil and aquatic bacteria, the accumulation of these benzamine compounds in the environment may have an adverse impact on soil biochemical activities. /2,5-diaminotoluene/

Redness.

Redness.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of November 6, 2012: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=6369-59-1]

The ability of 2,5-toluenediamine sulfate to induce morphological transformation in Syrian golden hamster embryo cells (Cell Transformation Assay) was evaluated prior to and after Simian adenovirus 7 inoculation. 2,5-Toluenediamine was tested in duplicate, at concentrations of 3.13, 6.25, 12.5, 25 or 50ug/ml prior to virus inoculation, resulting in a range of 100% to 25% relative survival (trial I) and 100% to 47% relative survival (trial II). Assays preformed after virus inoculation at concentrations of 1.00, 1.50, 2.24, 3.34 or 5.00ug/ml, resulting in a range of 100% to 23% relative survival. In a second trial, assays performed after virus inoculation at concentrations of 1.00, 1.78, 3.16, 5.62 or 10.0ug/ml, resulting in a range of 100% to 0% relative survival. At least one of the treatments in all four trials produced greater transformation frequencies (p < 0.01) relative to the negative control. A dose-response relationship was also observed.

The ability 2,5-toluenediamine sulfate to induce 6-thioguanine resistant mutants of Chinese hamster ovary (CHO) cells was evaluated in the presence and absence of Aroclor-induced rat liver S9 metabolic activation. Nonactivated cultures were tested at concentrations up to 50ug/mL, and activated cultures were tested at concentrations up to 750ug/mL. Choice of test concentrations and relative growth after treatment were not reported. 2,5-Toluene diamine sulfate produced mutant frequencies greater than the negative control with and without metabolic activation, but a dose-response was not observed.

The mutagenicity of 2,5-toluenediamine sulfate was evaluated in Salmonella tester strains TA98, TA100, TA1535, TA1537 and TA1538 (Ames Test), both in the presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Based on preliminary toxicity determinations, 2,5-toluenediamine sulfate, was tested at concentrations up to 5000ug/plate using the plate incorporation technique. 2,5-Toluenediamine sulfate produced a positive response in tester strains TA98, TA100, TA1537 and TA1538 with metabolic activation, and a clear dose-response was observed.

The effect of 2,5-toluenediamine sulfate (TDS) on testicular DNA synthesis was evaluated in Charles River mice. Animals were sacrificed and testes removed 3.5 hours following administration of test article at 63 mg/kg by intraperitoneal injection in one test and at 32 mg/kg in a second test. In the first test (63 mg/kg) TDS statistically significantly (t-test, p < 0.01) inhibited testicular DNA synthesis as measured by the amount of tritiated thymidine incorporated into DNA of testes homogenates from treated (1.85 dpm/ug) vs control animals (19.09 dpm/ug). In the second test (32 mg/kg), significant inhibition was not observed (p > 0.10).

/HUMAN EXPOSURE STUDIES/ The degree and pattern of hand eczema in hairdresser trainees and hairdressers was compared in Norway. 75 hairdressers affected by hand eczema and 74 hairdresser trainees with or without hand eczema were examined and patch tested with a hairdressers' series and some additional substances from the standard series. 2.7% of the hairdressers affected by hand eczema were test positive to toluene-2,5-diamine sulfate, compared to 0% of the hairdresser trainees.

/HUMAN EXPOSURE STUDIES/ 103 hairdressers (not dermatitis patients) in the Netherlands (96 females and 8 males) were patch tested with a special series including standard allergens and hairdressers' allergens. 2% were positive to toluene-2,5-diamine sulfate, 6% to p-phenylenediamine and 4% to 2-nitro-4-phenylenediamine.

/HUMAN EXPOSURE STUDIES/ In a multi-center study by the German Contact Dermatitis Group (DKG), 178 dermatitis patients (hairdressers) were patch tested with hairdressers' allergens in 11 centers. 18.0% were test positive to toluene-2,5-diamine, 8.4% to toluene-2,5-diamine sulfate, 18.0% to p-phenylenediamine base, 0.6% to resorcinol, 1.1% to 3-aminophenol, 2.2% to p-aminodiphenylamin hydrochloride, 3.4% to 4-aminophenol and 6.2% to o-nitro-p-phenylendiamine.

/HUMAN EXPOSURE STUDIES/ In a multi-center study by the Italian Contact Dermatitis Research Group (GIRDCA), a total of 302 dermatitis patients (hairdressers) (259 females and 43 males) were patch tested with hairdressers' allergens in 9 Italian centers. 13.2% were positive to toluene-2,5-diamine sulfate, 16.6% to p-phenylenediamine base (in 1989-1990), 7.6% to p-phenylenediamine dihydrochloride (in 1985-1988), 7.9% to o-nitro-p-phenylenediamine, 1.3% to resorcinol and 10.6% to p-aminodiphenylamine.

For more Human Toxicity Excerpts (Complete) data for 2,5-DIAMINOTOLUENE SULFATE (10 total), please visit the HSDB record page.

2,5-Toluenediamine sulfate

TR-126: Bioassay of 2,5-Toluenediamine Sulfate for Possible Carcinogenicity (CASRN 6369-59-1) (1978 )

06/25/78

No Evidence

No Evidence

No Evidence

/LABORATORY ANIMALS: Acute Exposure/ The ocular irritancy potential of toluene-2,5-diamine sulfate was studied using the chorioallantoic membrane of 6 freshly fertilized White Leghorn chicken eggs in a Hen's Egg Test Chorioallantoic Membrane (HET-CAM) test. The test material was undiluted (99.9% pure) and was applied to the chorioallantoic membrane and rinsed off with physiological saline after 30 seconds. Texapon ASV 70 (sodium magnesium laurylmyristyl-6-ethoxysulfate) at a concentration of 5% was used as a reference material, as it is defined as moderately irritating to rabbit eyes in vivo. End points of hemorrhage, coagulation, and blood vessel lysis were semi-quantitatively scored at 30 seconds (for the reference material) or 180 seconds (for the test material) after rinsing. The end points were scored as 0, 0, and 0, respectively, for toluene-2,5-diamine sulfate. In the reference material, the end points were 12, 9, and 0, respectively.

/LABORATORY ANIMALS: Acute Exposure/ A 10% concentration of toluene-2,5-diamine sulfate was administered to CFY strain rats (groups of 5 per sex) by oral intubation at doses of 0, 64, 100, 160, or 250 mg/kg of body weight. Treatment-related effects included lethargy, piloerection, ataxia, and increased salivation. Respiratory rates were increased in the 100-mg/kg dose group and decreased in the dose groups above 100 mg/kg. ...Necropsies were performed on the surviving rats. No abnormalities indicative of residual systemic effects were observed.

/LABORATORY ANIMALS: Acute Exposure/ The aim was to assess the skin sensitizing potency in the guinea pig of ten dye intermediates, including toluene-2,5-diamine sulphate, and to compare the results with results from patch testing hair coloring dermatitis patients in Japan. The study was performed by a non-guideline method. Pre-tests were performed by occluded exposure to determine the irritancy threshold. Topical induction was performed by occluded exposure for 48 hours on the nape, 3 times per week for two weeks. Following a 2 week rest period, challenge was performed by occluded exposure for 48 hours on the flank. Readings were made at 24 and 48 hours after removal of the test material. It was reported that 40% of the animals were positive to toluene-2,5-diamine sulfate at challenge with 1%, and 10% at challenge with 0.10%.

/LABORATORY ANIMALS: Acute Exposure/ The skin sensitizing potential of 2-methyl-1,4-benzenediamine sulfate was investigated by measuring the cell proliferation in the draining lymph nodes after topical application on the ear. 25 uL containing 0 (vehicle only), 0.5, 1.5 and 5.0% of the test substance in DMSO were applied to the surface of the ear to each of five mice per group for three consecutive days. p-Phenylenediamine (PPD) at 1% in DMSO was used as the positive control in parallel under identical test conditions. On day 5, the mice received an intravenous injection of 250 uL phosphate buffered saline containing 20 uCi of (3)H-methyl thymidine. Approximately five hours later, the mice were sacrificed by CO2-inhalation and the draining auricular lymph nodes were removed. After preparing a single cell suspension for each mouse, cells were precipitated by TCA and the radioactivity was determined (incorporation of (3)H-methyl thymidine in the pellets) by means of liquid scintillation counting as disintegration per minute (dpm). The mean dpm per treated group was determined and the stimulation index (test item compared to the concurrent vehicle control) was calculated. Mean stimulation indices (SI) of 4.9, 4.2, and 3.7 were obtained for the test concentrations of 0.5, 1.5 and 5%, respectively. No EC3 value was calculated, since all stimulation indices were above 3. The positive control (PPD 1% in DMSO) caused a stimulation index of 10.

For more Non-Human Toxicity Excerpts (Complete) data for 2,5-DIAMINOTOLUENE SULFATE (36 total), please visit the HSDB record page.

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. 1,4-Benzenediamine, 2-methyl-, sulfate is included on this list. Effective date: 4/29/83; Sunset date: 4/29/93.

Incubation of the (14)C-toluene-2,5-diamine sulfate with the human hepatocytes yielded an acetylated metabolite but no sulfated, glucuronidated, or monohydroxylated metabolites.

Three major metabolites were observed in the urine /of female Wistar Kyoto rats/ after oral dosing /of (14)C-toluene-2,5-diamine sulfate/, with the main metabolite identified as N,N-diacetyl-toluene-2,5-diamine. No parent compound was identified in the urine. Radioactivity in the urine of the dermal dose group was too low for separation and detection of metabolites.

2,5-Diaminotoluene sulfate is absorbed through the skin of dogs and excreted in the urine. About 40 mg of the compound were absorbed from 50 mL of a lauryl sulfate-based gel containing 1.4 g 2,5-diaminotoluene within 3 hr. When 6% hydrogen peroxide was added to the gel immediately before use, the amount of 2,5-diaminotoluene sulfate absorbed was less than 3 mg

Ten milligrams of 2,5-diaminotoluene sulfate (equivalent to 5.54 mg 2,5- diamino-toluene) injected subcutaneously into six adult volunteers were excreted in the urine as the N,N'-diacetyl derivative, which accounted for approximately half of the injected dose, over 48 hr. During the process of hair dyeing with a dye formulation in which a total of 2.5 g 2,5-diaminotoluene sulfate were applied in conjunction with 6% hydrogen peroxide added just before application, it was estimated that 4.6 mg 2,5-diaminotoluene sulfate had been absorbed through the skin of five volunteers.

The absorption and elimination of toluene-2,5-diamine were studied in 5 male human subjects. A test formulation was prepared with [Me-(14)C]-toluene-2,5-diamine plus unlabeled toluene-2,5-diamine sulfate in a hair dye cream formulation containing 0.825% resorcinol. The final concentration of toluene-2,5-diamine sulfate was 1.65%. This formulation was then mixed with either 100 g of water (1:1) or 100 g of 6% hydrogen peroxide to produce formulation 1 and formulation 2, respectively. The subjects received 1 of the 2 formulations (45 g, containing a total of 371 mg of toluene-2,5-diamine) on a 250-sq cm area of the scalp. The formulation was thoroughly rinsed off after 30 minutes and the hair was shampooed. The mean total elimination rate of radioactivity of the applied dose in the urine and the feces was 4.81% +/-0.62% for formulation 1 and 1.31% +/- 0.14% in formulation 2. The amounts of toluene-2,5-diamine sulfate were 71 +/- 9.26 mgeq/ sq cm for formulation 1 and 20 +/- 2.02 mgeq/sq cm for formulation 2. The area under the curve (AUC) for whole blood recovery was 41.6 +/- 1.7 ngeq.hr/L and 9.2 +/- 3.1 ngeq.hr/L for formulations 1 and 2, respectively. The total recovery for formulation 1 was 91.2% +/- 1.73%, whereas the total recovery for formulation 2 was 47.64% +/- 3.43%. The authors concluded that the lower recovery for formulation 2 was due to higher retention of radiolabel in the hair as a result of the oxidative hair coloring process.

Percutaneous absorption of toluene-2,5-diamine sulfate in human skin samples was studied... Radiolabeled (97.2% pure) and non-radiolabeled (99.7% pure) toluene-2,5-diamine sulfate was added to a final concentration of 9% to 2 hair dye bases, one of which contained an equimolar amount of m-aminophenol as a coupler. The formulation containing the coupler was mixed with hydrogen peroxide (50:50) to yield a test substance with a final toluene-2,5-diamine sulfate concentration of 4.5%. The formulation base without the coupler was mixed with water or hydrogen peroxide, in both cases 50:50, to yield 2 other test substances with final concentrations of toluene-2,5-diamine sulfate of 4.5%. The formulations were then applied over an area of 2-sq cm to 350-mm-thick human skin (20 mg/sq cm) or samples of isolated epidermis mounted in perfusion cells. After an application period of 30 minutes, the test substance was rinsed off with water and a solution of sodium lauryl sulfate. Most of the test substance (93.5% of the applied dose) was recovered during rinsing at 30 minutes post application. Cumulative penetration (based on radioactivity in the receptor fluid) neared a plateau at approximately 5 hours. The total absorption in the formulation without coupler mixed with water was 4.17% +/- 2.54% (40.31 +/- 23.77 mgeq/sq cm). In the formulations mixed with peroxide, the total absorption was 3.41% +/- 1.32% (31.26 +/- 11.64 mgeq/sq cm) with the coupler and 3.44% +/- 2.84% (32.03 +/- 26.58 mgeq/sq cm) without the coupler.

The absorption, distribution, metabolism, and excretion of (14)C-toluene-2,5-diamine sulfate were investigated in rats in a series of studies... Groups of female Wistar Kyoto rats (4 per group in the mass balance portion of the study and 6 per group in the toxicokinetics portion of the study) received the test substance at either 2.5 or 25.0 mg/kg of body weight in a single oral gavage dose or at 33.3 mg/kg of body weight as a dermal application. Vehicle for the oral groups was water, whereas in the dermal group it was water/acetone (1:1). In the urine of the oral dose groups after 96 hours, the mean cumulative recovery of the applied dose was 62.2% in the 2.5-mg/kg dose group and 72.9% in the 25-mg/kg dose group, whereas in the feces, the recovery was 31.4% and 22.0%, respectively. The mean mass balance for both oral doses was about 98%. In the dermal application groups, 10.9% and 2.7% of the applied dose were recovered in the urine and feces, respectively. The mean mass balance for the dermal dose was nearly 100%. ...In plasma kinetics results, the time to peak concentration (Tmax) was 0.5 hours and 0.25 hours for the low- and high-dose oral groups, respectively, indicating rapid absorption. The AUC values for the 2 oral dose groups were 17.59 and 174 mgeq.hr/L, respectively, and for the dermal dose group 4.39 mgeq.hr/L.

CIR ingredient: Toluene-2,5-Diamine Sulfate

Used in hair dyes, bleach-toner formulas, and brown fur dyes; [HSDB]

Fur Dressing and Dyeing [Category: Industry]

Used in hair dyes; [EC - SCCS]

Dressing Hair [Category: Other]

Used as ingredients in the formulation of permanent hair dyes, colors, and tints

The Scientific Committee on Consumer Products also reported that toluene-2,5-diamine sulfate (concentration of solution not provided) had greater than 98% wt/wt HPLC quantitative purity, greater than 99% HPLC qualitative (254 nm) purity, a solvent content less than 1%, and the potential impurity o-toluidine less than 50 ppm.

(1976) 1.30X10+6 G (PRINCPL CUSTMS DISTS)

(1978) 5.87X10+6 G (PRINCPL CUSTMS DISTS)

1,4-Benzenediamine, 2-methyl-, sulfate (1:1): ACTIVE

1,4-Benzenediamine, 2-methyl-, sulfate (1:?): ACTIVE

According to a survey of current use concentrations conducted by the Cosmetic, Toiletry, and Fragrance Association (CTFA), ... toluene-2,5-diamine sulfate is used at concentrations of 0.1% to 4.0%in hair dyes and colors and at 3% in hair bleaches.

2,5-Diaminotoluene sulfate was first produced commercially in the USA in 1927.