o-Tolidine

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

H350: May cause cancer [Danger Carcinogenicity]

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

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

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

H350 (100%): May cause cancer [Danger Carcinogenicity]

H411 (100%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

Aggregated GHS information provided per 53 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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.

H372: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

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

P260, P264, P270, P319, and P501 (click each P-code to see the statement)

H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]

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

P203, P260, P264, P270, P273, P280, P301+P317, P318, P319, P330, P391, P405, and P501 (click each P-code to see the statement)

P273, P391, and P501 (click each P-code to see the statement)

H351: Suspected of causing cancer [Warning Carcinogenicity]

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

Fresh air, rest.

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

Rinse with plenty of water (remove contact lenses if easily possible).

Rinse mouth. Give one or two glasses of water to drink.

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. IMMEDIATELY call a hospital or poison control center even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas.

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)

(General first aid procedures)

Eye: Irrigate immediately - If this chemical contacts the eyes, immediately wash (irrigate) the eyes with large amounts of water, occasionally lifting the lower and upper lids. Get medical attention immediately.

Skin: Soap flush immediately - If this chemical contacts the skin, immediately flush the contaminated skin with soap and water. If this chemical penetrates the clothing, immediately remove the clothing and flush the skin with water. If irritation persists after washing, get medical attention.

Breathing: Respiratory support

Swallow: Medical attention immediately - If this chemical has been swallowed, get medical attention immediately.

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

Use powder, water spray, foam, carbon dioxide.

Personal protection: chemical protection suit including self-contained breathing apparatus. Do NOT let this chemical enter the environment. Sweep spilled substance into sealable containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

A new method developed for the removal of carcinogenic aromatic amines from industrial aqueous effluents uses horseradish peroxidase & hydrogen peroxide resulting in a nearly complete precipitation of carcinogenic aromatic amines from water due to enzymatic crosslinking.

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/

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U095, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A good candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

It is shown that the oxidation of benzidine, o-tolidine, and o-dianisidine with potassium permanganate in a sulfuric acid medium results in a deep destruction of these substances in which more than 99.8% of the original compounds is destroyed.

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/

For more Disposal Methods (Complete) data for 3,3'-DIMETHYLBENZIDINE (11 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 3,3'-DIMETHYLBENZIDINE (16 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 protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)

Separated from strong oxidants and food and feedstuffs. Well closed. Store in an area without drain or sewer access. Provision to contain effluent from fire extinguishing.

... Protected from light.

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/

0.0018 [mg/m3]

0.020 [mg/m3]

36 [mg/m3]

0.02 mg/m³ [60 minutes]

Ca C 0.02 mg/m3 [60-minute] [skin] See Appendix ASee Appendix C

See Appendix C

A potential occupational carcinogen. (NIOSH, 2024)

NIOSH considers o-tolidine to be a potential occupational carcinogen.

Ca [N.D.]

See: IDLH INDEX

Notations: Skin.

A3; Confirmed animal carcinogen with unknown relevance to humans.

(skin); A3 (confirmed animal carcinogen with unknown relevance to humans).

carcinogen category: 2

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

This substance is probably carcinogenic to humans.

Excerpt from NIOSH Pocket Guide for o-Tolidine:

Skin: PREVENT SKIN CONTACT - Wear appropriate personal protective clothing to prevent skin contact.

Eyes: PREVENT EYE CONTACT - Wear appropriate eye protection to prevent eye contact.

Wash skin:

• WHEN CONTAMINATED - The worker should immediately wash the skin when it becomes contaminated.

• DAILY - The worker should wash daily at the end of each work shift, and prior to eating, drinking, smoking, etc.

Remove: WHEN WET OR CONTAMINATED - Work clothing that becomes wet or significantly contaminated should be removed and replaced.

Change: DAILY - Workers whose clothing may have become contaminated should change into uncontaminated clothing before leaving the work premises.

Provide:

• EYEWASH - Eyewash fountains should be provided in areas where there is any possibility that workers could be exposed to the substances; this is irrespective of the recommendation involving the wearing of eye protection.

• QUICK DRENCH - Facilities for quickly drenching the body should be provided within the immediate work area for emergency use where there is a possibility of exposure. [Note: It is intended that these facilities provide a sufficient quantity or flow of water to quickly remove the substance from any body areas likely to be exposed. The actual determination of what constitutes an adequate quick drench facility depends on the specific circumstances. In certain instances, a deluge shower should be readily available, whereas in others, the availability of water from a sink or hose could be considered adequate.] (NIOSH, 2024)

Wear protective gloves and clothing to prevent any reasonable probability of skin contact... All protective clothing (suits, gloves, footwear, headgear) should be clean, available each day, and put on before work... Wear dust-proof chemical goggles and face shield unless full-face-piece respirator protection is worn...

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/

Use closed system or ventilation.

Wear appropriate personal protective clothing to prevent skin contact.

For more Personal Protective Equipment (PPE) (Complete) data for 3,3'-DIMETHYLBENZIDINE (9 total), please visit the HSDB record page.

At concentrations above the NIOSH REL, or where there is no REL, at any detectable concentration:

(APF = 10,000) Any self-contained breathing apparatus that has a full facepiece and is operated in a pressure-demand or other positive-pressure mode

(APF = 10,000) Any supplied-air respirator that has a full facepiece and is operated in a pressure-demand or other positive-pressure mode in combination with an auxiliary self-contained positive-pressure breathing apparatus

(APF = 50) Any air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted organic vapor canister having an N100, R100, or P100 filter.

Click here for information on selection of N, R, or P filters.

Any appropriate escape-type, self-contained breathing apparatus

Important additional information about respirator selection

NO open flames.

3,3'-dimethylbenzidine appears as white to reddish crystals or crystalline powder or a light tan powder. (NTP, 1992)

White to reddish crystals or powder. [Note: Darkens on exposure to air. Often used in paste or wet cake form. Used as a basis for many dyes.]; [NIOSH]

COLOURLESS CRYSTALS OR RED-TO-BROWN FLAKES.

White to reddish crystals or powder.

White to reddish crystals or powder. [Note: Darkens on exposure to air. Often used in paste or wet cake form. Used as a basis for many dyes.]

Colorless; in technical grades also brownish flakes

White to reddish crystals or powder [Note: Darkens on exposure to air]

392 °F at 760 mmHg (NTP, 1992)

300 °C @760 [mm Hg]

264 to 268 °F (NTP, 1992)

129-131 °C

MP: 264 °F

131-132 °C

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

In water, 1,300 mg/L at 25 °C

Soluble in alcohol, ether, dilute acids

Solubility in water, g/100ml at 25 °C: 0.13 (poor)

1 (NTP, 1992)

1.234 g/cu cm

1.2 g/cm³

0.000001 [mmHg]

1x10-6 mmHg (est)

log Kow = 2.34

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

Liquid: 964.3 kg.cal

pKa1 = 4.5; pKa2 = 3.3 (conjugate acid)

166.2 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID6020511]

150.8 Ų [M]+ [CCS Type: DT; Buffer gas: N2; Ionization: APCI+; Dataset: TOXCAST; Source Identifier: DTXSID5024059]

151.9 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: APCI+; Dataset: TOXCAST; Source Identifier: DTXSID6020511]

166.5 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID5024059]

166.1 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: APCI+; Dataset: TOXCAST; Source Identifier: DTXSID5024059]

150.7 Ų [M]+ [CCS Type: DT; Buffer gas: N2; Ionization: APCI+; Dataset: TOXCAST; Source Identifier: DTXSID6020511]

Barely becomes discolored upon exposure to air. It is chemically resistant to water.

Crystal structure

Formula unit

Magnetic anisotropy

Space group

Unit cell

Unit cell parameter

Hazardous Air Pollutants (HAPs)

Insoluble in water.

Amines, Aromatic

3,3'-DIMETHYLBENZIDINE is sensitive to exposure to light. May be sensitive to prolonged exposure to air. A weak base that forms salts with hydrochloric acid or sulfuric acid. It can be acetylated. Incompatible with strong agents (NTP, 1992).

Strong oxidizers.

Strong oxidizers

3,3-Dimethylbenzidine

This substance/agent has not undergone a complete evaluation under U.S. EPA's IRIS program for evidence of human carcinogenic potential.

No data are available in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 2B: The agent is possibly carcinogenic to humans.

A3; Confirmed animal carcinogen with unknown relevance to humans.

3,3'-Dimethylbenzidine: reasonably anticipated to be a human carcinogen. /3,3'-Dimethylbenzidine and Dyes Metabolized to 3,3'-Dimethylbenzidine/

3,3'-Dimethylbenzidine (ortho-Tolidine)

Group 2B: Possibly carcinogenic to humans

Volume 1: (1972) Some Inorganic Substances, Chlorinated Hydrocarbons, Aromatic Amines, N-Nitroso Compounds, and Natural Products

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)

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

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

MAY BE ABSORBED! See EFFECTS OF LONG-TERM OR REPEATED EXPOSURE.

irritation eyes, nose; In Animals: liver, kidney damage; [potential occupational carcinogen]

Eyes, respiratory system, liver, kidneys

[in animals: liver, bladder & mammary gland tumors]

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.

IARC Carcinogen - Class 3: Chemicals are not classifiable by the International Agency for Research on Cancer.

NTP Carcinogen - Reasonably anticipated to be a human carcinogen.

ACGIH Carcinogen - Confirmed Animal.

3,3\'-Dimethylbenzidine

PDF Document

Likely to be carcinogenic to humans

PPRTV Current

... Elevated risk for cancer of the urinary bladder has been found in workers employed in dye manufacture, and those exposted to combination of benzidine and o-Tolidine...

There is some evidence that concurrent exposure to o-tolidine decreased the time to appearance of tumors in rats treated with benzidine.

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. /Aniline 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 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 ... . /Aniline 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. 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. Consider vasopressors if hypotensive with a normal fluid volume. 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 or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Aniline and related compounds/

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/

/OTHER TOXICITY INFORMATION/ ... Vapor toxicity was much like that of aniline (slight symptoms after several hr at 6 to 23 ppm & 7 to 53 ppm respectively).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Male and female F344/N rats given o-tolidine dihydrochloride in drinking water at 600, 1250, 2500, 5000, or 7500 ppm for 14 days showed dose-related mortality and inanition. Necrotic hepatocytes, nephropathy, and bone marrow depression were seen in rats given 2500 ppm o-Tolidine...

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Female Sprague-Dawley rats were given, by stomach tube, suspension of o-Tolidine in sesame oil up to total dose of 500 mg/rat, fractionated in 10 doses at 3-day intervals. Rats were alive at end of the observation period, ie, 9 mo: 3 of these showed total of 4 mammary carcinomas. In comparison, four out of five animals that survived after being given benzidine (50 mg per rat) showed a total of 17 mammary carcinomas. Among 132 rats that received the solvent only, 5 had a total of 3 mammary carcinomas, 1 fibroadenoma and 5 hyperplasias.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Commercial o-Tolidine at dietary level of 0.1% (3.0 g/animal/yr) fed to groups of 30 male and 30 female hamsters throughout their life-span did not induce bladder or other tumors. Negative results were also obtained at dietary level of 0.3%, which was highest tolerated level. Commercial o-Tolidine in olive oil was given as a weekly SC injection, at a dose level of 60 mg/rat/wk (total dose: 5.5 g), to 105 sherman rats. Survived more than 300 days and were kept throughout their lifespan. In contrast to rats given benzidine, no cirrhosis or hepatomas were observed among those receiving o-Tolidine. Rats developed cancer of external auditory canal, all tumors appearing after 354th day. No control group was run at the same time. Out of 56 tumors occurring among 578 untreated rats of the same colony, none was located in the external auditory canal.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Random bred rats received weekly SC injections of purified o-tolidine in sunflower oil for 13 mo, at doses of 20 mg/rat/wk. Among 50 animals that survived for 8 MO (time of occurrence of 1St tumor), 30 developed total of 41 tumors. Carcinomas of zymbal's gland, & tumors at other sites were seen. Additional groups of rats ... received weekly SC implant of pellet containing 20 mg of purified o-Tolidine & 10 mg of glycerol for 14 MO. In second of these groups o-tolidine had been subjected to UV irradiation prior to preparation of the pellet. The difference between the 2 groups was minimal. Of the total of 68 animals that were alive at the time of appearance of the first tumor (11-12 mo), 48 developed a total of 60 tumors. Among these were 27 zymbal's gland carcinomas and tumors at other sites. No control group was run at the same time as these experiments, but in a preliminary report on these studies it was stated that rats from the same colony did not develop tumors of zymbal's gland.

For more Non-Human Toxicity Excerpts (Complete) data for 3,3'-DIMETHYLBENZIDINE (15 total), please visit the HSDB record page.

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 July 18, 2013: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=119-93-7]

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. /3,3'-Dimethylbenzidine dihydrochloride/[Available from, as of July 18, 2013: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=612-82-8]

Toxicology and carcinogenesis studies were conducted by administering 3,3'-dimethylbenzidine dihydrochloride (approximately 99% pure) in drinking water to groups of F344/N rats of each sex for ... 14 months. The 14-month exposures were planned as 24-month exposures but were terminated early because of rapidly declining animal survival, due primarily to neoplasia. The average amount of 3,3'-dimethylbenzidine dihydrochloride consumed per day was approximately 1.8, 4.0, or 11.2 mg/kg for low-, mid-, or high-dose male rats and 3.0, 6.9, or 12.9 mg/kg for low-, mid-, or high-dose female rats. ... Because of extensive neoplasia, many exposed males and females were dying or were sacrificed moribund in the first year, and all high-dose males died by week 55. The studies were terminated at weeks 60 to 61, at which time the group survivals were male; control, 60/60; low dose, 41/45; mid dose, 50/75; high dose, 0/60; female: 59/60; 39/45; 27/75; high dose, 0/60; female: 59/60; 39/45; 32/75; 10/60. ... There was clear evidence of carcinogenic activity of 3,3'-dimethylbenzidine dihydrochloride for male F344/N rats, as indicated by benign and malignant neoplasms of the skin, Zymbal's gland, preputial gland, liver, oral cavity, small and large intestine, lung, and mesothelium. Increased incidences of neoplasms of the brain may have been related to chemical administration. There was /also/ clear evidence of carcinogenic activity for female F344/N rats, as indicated by benign and malignant neoplasms of the skin, Zymbal's gland, clitoral gland, liver, oral cavity, small and large intestine, mammary gland, and lung. Increased incidences of neoplasms of the brain and mononuclear cell leukemia may have been related to chemical administration. /3,3'-Dimethylbenzidine dihydrochloride/

EC50; Species: Daphnia magna (Water Flea); Conditions: freshwater, renewal, 25 °C, pH >7; Concentration: 3200 ug/L for 24 hr; Effect: behavior, equilibrium /formulation/

EC50; Species: Daphnia magna (Water Flea) age < or =24 hr; Conditions: freshwater, static, 25 °C, pH > or =7, dissolved oxygen > or =58%; Concentration: 3200 ug/L for 24 hr; Effect: intoxication, immobilization /formulation/

EC50; Species: Daphnia magna (Water Flea); Conditions: freshwater, renewal, 25 °C, pH >7; Concentration: 3200 ug/L for 24 hr; Effect: behavior, equilibrium /formulation/

EC50; Species: Daphnia magna (Water Flea) age < or =24 hr; Conditions: freshwater, static, 25 °C, pH > or =7, dissolved oxygen > or =58%; Concentration: 3200 ug/L for 24 hr; Effect: intoxication, immobilization /formulation/

1.10e-02

2.10e-01

2.10e-03

5.00e+00

1.10e+01

Volatile

1.10e+00

2.10e+01

The substance is toxic to aquatic organisms. It is strongly advised not to let the chemical enter into the environment.

3,3'-Dimethylbenzidine's production and use as a chemical intermediate in the production of dyes and as a reagent for the detection of gold and free chlorine in water may result in its release to the environment through various waste streams. 3,3'-Dimethylbenzidine has been detected as a biodegradation degradation product of various azo dyes. If released to air, an estimated vapor pressure of 1.0X10-6 mm Hg at 25 °C indicates 3,3'-dimethylbenzidine will exist in both the vapor and particulate in the atmosphere. Vapor-phase 3,3'-dimethylbenzidine 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 2 hours. Particulate-phase 3,3'-dimethylbenzidine will be removed from the atmosphere by wet and dry deposition. 3,3'-Dimethylbenzidine absorbs at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, 3,3'-dimethylbenzidine is expected to have slight mobility based upon an estimated Koc of 3200. The pKa values of 3,3'-dimethylbenzidine are 4.50 and 3.3, indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Stronger adsorption of protonated 3,3'-dimethylbenzidine has been observed in sorption studies. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 6.3X10-11 atm-cu m/mole. 3,3'-Dimethylbenzidine is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Utilizing the Japanese MITI test, 3% of the Theoretical BOD was reached in 4 weeks indicating that 3,3'-dimethylbenzidine is not readily biodegradable. Benzidine and its derivatives are known to be rapidly oxidized by Fe(III) and other cations which are frequently found in soil and environmental waters. If released into water, 3,3'-dimethylbenzidine is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. BCF values in the range of 4.8 to 83, measured in fish, suggests bioconcentration in aquatic organisms is low to moderate. 3,3'-Dimethylbenzidine is not expected to undergo hydrolysis due to a lack of hydrolyzable functional groups. Direct photolysis and photo-oxidation may be important fate processes in natural waters exposed to sunlight. Occupational exposure to 3,3'-dimethylbenzidine may occur through inhalation and dermal contact with this compound at workplaces where 3,3'-dimethylbenzidine is produced or used. (SRC)

3,3'-Dimethylbenzidine's production and use as a chemical intermediate in the production of dyes and as a reagent for the detection of gold and free chlorine in water(1) may result in its release to the environment through various waste streams(SRC). 3,3'-Dimethylbenzidine has been detected as a biodegradation product of various azo dyes(2).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3190(SRC), determined from a structure estimation method(2), indicates that 3,3'-dimethylbenzidine is expected to have slight mobility in soil(SRC). The pKa values of 3,3'-dimethylbenzidine are 4.50 and 3.3(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). In sediment studies, sorption measurements over the pH range of 5 to 9 saw an increase in sorption as the pH decreased suggesting that the protonated form of 3,3'-dimethylbenzidine was more strongly bound than the neutral form(5). Volatilization of 3,3'-dimethylbenzidine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.3X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(2). 3,3'-Dimethylbenzidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.0X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). 3,3'-Dimethylbenzidine, present at 100 mg/L, reached 3% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L and the Japanese MITI test(6), indicating the compound is not readily biodegradable(6). 3,3'-Dimethylbenzidine absorbs light >290 nm(7) and may be susceptible to direct photolysis by sunlight on soil surfaces(SRC). Benzidine is rapidly oxidized by Fe(III) and several other cations which are frequently found in environmental soils and clays(8) which suggest that 3,3'-dimethylbenzidine may also be degraded by a similar process(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3190(SRC), determined from a structure estimation method(2), indicates that 3,3'-dimethylbenzidine 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 6.3X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(7), BCF values in the range of 4.8 to 83(4), measured in carp (Cyprinus carpio), suggest bioconcentration in aquatic organisms is low to moderate(SRC). 3,3'-Dimethylbenzidine, present at 100 mg/L, reached 3% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L and the Japanese MITI test(6), indicating the compound is not readily biodegradable(5). 3,3'-Dimethylbenzidine absorbs light >290 nm(6) and may be susceptible to direct photolysis. When aerated solutions of benzidine were exposed to a light from a xenon lamp (300-400 nm) complete degradation of benzidine was observed in 12 hours(7); photodegradation of 3,3'-dimethylbenzidine may be similar(SRC). Aromatic amines are susceptible to photooxidation in natural waters via reaction with OH and RO2 radicals with half-lives on the order of a few days or less(8), therefore, photooxidation may be an important fate process for 3,3'-dimethylbenzidine in sunlit natural water(SRC). Benzidine is rapidly oxidized by Fe(III) and several other cations which are frequently found in environmental soils and clays(9) which suggests that 3,3'-dimethylbenzidine may also be degraded by a similar process(SRC). 3,3'-Dimethylbenzidine is not expected to undergo hydrolysis due to a lack of hydrolyzable functional groups(3).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 3,3'-dimethylbenzidine, which has an estimated vapor pressure of 1.0X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 3,3'-dimethylbenzidine 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 1.9X10-10 cu cm/molecule-sec at 25 °C (SRC)determined using a structure estimation method(2). 3,3'-Dimethylbenzidine absorbs light >290 nm(3), therefore, it may be susceptible to direct photolysis(SRC). Particulate-phase 3,3'-dimethylbenzidine may be removed from the air by wet and dry deposition(SRC).

AEROBIC: In a Warburg respirometer that used activated sludge from both domestic and industrial discharges, 100% of the 3,3'-dimethylbenzidine (initial concentration 20 mg/L) was depleted in 6 hours at 25 °C(1). 3,3'-Dimethylbenzidine, present at 100 mg/L, reached 3% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L and the Japanese MITI test(2,3), indicating the compound is not readily biodegradable(3).

The rate constant for the vapor-phase reaction of 3,3'-dimethylbenzidine with photochemically-produced hydroxyl radicals has been estimated as 1.9X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 3,3'-Dimethylbenzidine absorbs light greater than 290 nm(2) and may be susceptible to direct photolysis by sunlight(SRC). When aerated solutions of benzidine were exposed to a light from a xenon lamp (300-400 nm) complete degradation of benzidine was observed in 12 hours(3); photodegradation of 3,3'-dimethylbenzidine may be similar(SRC). Aromatic amines are susceptible to photooxidation in natural waters via reaction with OH and RO2 radicals with half-lives on the order of a few days or less(4), therefore, photooxidation may be an important fate process for 3,3'-dimethylbenzidine in sunlit natural water(SRC). 3,3'-Dimethylbenzidine is chemically resistant to water(5) and not expected to undergo hydrolysis due to a lack of hydrolyzable functional groups(6). Benzidine is rapidly oxidized by Fe(III) and several other cations which are frequently found in environmental water and soil(7); 3,3'-dimethylbenzidine may be susceptible to the same degradation process(SRC).

Using carp (Cyprinus carpio) which were exposed over an 8-week period in a continuous flow system and 3,3'-dimethylbenzidine concentrations of 0.02 and 0.2 mg/L, a 3,3'-dimethylbenzidine BCF range of 4.8 to 83 was measured(1). According to a classification scheme(2), these BCF values suggest bioconcentration in aquatic organisms is low to moderate(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 3,3'-dimethylbenzidine can be estimated to be 3190(SRC). According to a classification scheme(2), this estimated Koc value suggests that 3,3'-dimethylbenzidine is expected to have slight mobility in soil. The pKa value of 3,3'-dimethylbenzidine are 4.50 and 3.3(3), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). In sorption studies using colloidal sediment collected from the Chesapeake Bay estuary, 3,3'-dimethylbenzidine had a colloid Koc value (Kcoll) of 2014(5); sorption measurements over the pH range of 5 to 9 saw a significant increase in sorption as the pH decreased suggesting that the protonated form of 3,3'-dimethylbenzidine was more strongly bound than the neutral form(5).

The Henry's Law constant for 3,3'-dimethylbenzidine is estimated as 6.3X10-11 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 3,3'-dimethylbenzidine is expected to be essentially nonvolatile from water surfaces(2). 3,3'-Dimethylbenzidine's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to be an important fate process(SRC). 3,3'-Dimethylbenzidine is not expected to volatilize from dry soil surfaces(SRC) based upon a an estimated vapor pressure of 1.0X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 9,369 workers (6,004 of these are female) are potentially exposed to 3,3'-dimethylbenzidine in the US(1). Occupational exposure to 3,3'-dimethylbenzidine may occur through inhalation and dermal contact with this compound at workplaces where 3,3'-dimethylbenzidine is produced or used(2).

Processes in which dried dye is handled have the greatest potential for employee exposure during the manufacture or repackaging of benzidine-based dyes. ... During use of benzidine-based dyes, the greatest potential for exposure would be expected to be among dye-weighers who handle dry powders. /Benzidine-based dyes/

o-Tolidine may enter the body by percutaneous absorption, by ingestion or by inhalation.

Most occupational exposures to o-tolidine actually involve a mixture of biphenyl amine compounds.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U095, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A good candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

It is shown that the oxidation of benzidine, o-tolidine, and o-dianisidine with potassium permanganate in a sulfuric acid medium results in a deep destruction of these substances in which more than 99.8% of the original compounds is destroyed.

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/

For more Disposal Methods (Complete) data for 3,3'-DIMETHYLBENZIDINE (11 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/

Do not transport with food and feedstuffs.

Symbol: T, N; R: 45-22-51/53; S: 53-45-61; Note: E