3,3'-Dimethyl-benzidin

Hazardous Air Pollutants (HAPs)

Nitrogen Compounds -> Benzidine and Derivatives

Carcinogens

log Kow = 2.34

2.34

1 (NTP, 1992)

1.234 g/cu cm

1.2 g/cm³

1

Colorless; in technical grades also brownish flakes

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

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)

0.1%

137 °C

244 °C

471 °F

392 °F at 760 mmHg (NTP, 1992)

300 °C

300 °C

392 °F

300 °C @760 [mm Hg]

572 °F

264 to 268 °F (NTP, 1992)

129-131 °C

MP: 264 °F

131-132 °C

264 °F

131 °C

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: [1,1'-Biphenyl]-4,4'-diamine, 3,3'-dimethyl-

Hazard Traits - Carcinogenicity; Respiratory Toxicity

[1,1'-Biphenyl]-4,4'-diamine, 3,3'-dimethyl-: HSNO Approval: HSR001543 Approved with controls

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.)

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

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

3,3'-Dimethylbenzidine is used as an intermediate in the production of dyes and pigments. Acute (short- term) exposure to high levels of 3,3'-dimethylbenzidine in humans may irritate the nose and throat. No information is available on the chronic (long-term), reproductive, developmental, or carcinogenic effects of 3,3'-dimethylbenzidine in humans. A study by the National Toxicology Program (NTP) reported that oral exposure to 3,3'-dimethylbenzidine dihydrochloride resulted in an increased incidence of tumors of the skin, liver, intestine, lung, and other organs. EPA has classified 3,3'-dimethylbenzidine as a Group B2, probable human carcinogen.

A carcinogen in experimental animals; [HSDB] In subchronic feeding studies, animals develop liver and kidney damage and bone marrow depression. [ACGIH] See Benzidine.

U.S. Department of Health & Human Services/National Toxicology Program; Twelfth Report on Carcinogens (2011). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. 3,3'-Dimethylbenzidine (119-93-7) was first listed in the Third Annual Report on Carcinogens (1983) as reasonably anticipated to be a human carcinogen and re-reviewed in the Tenth Report on Carinogens (2002). /3,3'-Dimethylbenzidine and Dyes Metabolized to 3,3'-Dimethylbenzidine/[Available from, as of July 17, 2013: http://ntp.niehs.nih.gov/]

Health hazard alert: benzidine-, o-tolidine-, & o-dianisidine-based dyes; dhhs (niosh) publ usa (81-106) 39 pp (1980). A review with 42 references on the health hazard of benzidine, o-tolidine, & o-dianisidine dyes & 118 dyes based on these cmpd.

USEPA; Health and Environmental Effects Profile for 3,3'-Dimethylbenzidine; Environmental Criteria and Assessment Office, Cincinnati, OH, EPA/600/X-87/391 (1987), NTIS PB89-119929

DHHS/NTP; Toxicology & Carcinogenesis Studies of 3,3'-Dimethylbenzidine Dihydrochloride in F344/N Rats (Drinking Water Studies) Technical Report Series No. 390 (1991) NIH Publication No. 91-2845

U095; As stipulated in 40 CFR 261.33, when 3,3'-dimethylbenzidine, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

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).

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. 3,3'-Dimethylbenzidine is included on this list.

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.

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.

(General first aid procedures)

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/

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.

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.

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/

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.

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.

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.

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.

... 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.

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/

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).

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]

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]

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/

U095; As stipulated in 40 CFR 261.33, when 3,3'-dimethylbenzidine, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. 3,3'-Dimethylbenzidine is included on this list.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 10 lb or 4.54 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

In mice and rats, prenatal exposure to the dye Congo red permanently reduces the number of germ cells in male and female offspring. In the current investigation, nine other dyes structurally related to Congo red were examined for developmental testicular toxicity. In this study, the structural component of the dyes responsible for the prenatal induction of germ cell aplasia was identified. /Investigators/ found that only benzidine-based dyes altered testicular development and caused hypospermatogenesis in mice during adulthood. Dimethyl- and dimethoxybenzidine-based dyes were without effect. Pregnant mice were dosed orally on Days 8-12 of gestation with a benzidine-, dimethylbenzidine-, or a dimethoxybenzidine-based dye and the testes of 45- to 50-day-old male offspring were examined. The testes of postpubertal male offspring exposed to the benzidine-based dyes, Congo red, diamine blue, and Chlorazol Black E, were small and contained some tubules completely devoid of germ cells, but the dimethylbenzidine-based dyes, trypan blue, Evans blue, and benzopurpurin 4B, and the dimethoxybenzidine-based dye, Chicago sky blue, did not alter testicular development in this manner. Azoic diazo component 48, a dimethoxybenzidine congener, and two other diazo dyes, naphthol blue black and Sudan III, were also without effect on the germ cells. Experiments with Chlorazol Black E (CBE) indicate that the period of susceptibility in the male fetus is limited to the period of primordial germ cell migration and division. When CBE was administered on Days 8-10 of gestation it reduced testis weight after puberty by 30%, while treatment after Day 13 did not affect testicular function.

It was found that intoxication of animals with aminobiphenyls leads to the activation of such glutathione-dependent enzymes as glutathione-S-transferase and glutathione reductase. This is accompanied by the induction of activities of individual isoforms of the multifunctional family of glutathione-S-transferases. There was a decrease in the glutathione peroxidase activity after intoxication with benzidine derivatives. It was found that the GSH content in rat liver decreased after benzidine intoxication and sharply increased after effects of 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine. In all cases studied there was a diminution in the level of diene conjugates. It was supposed that the specificity of the catalytic glutathione redox system reaction is due to structural peculiarities of the aminobiphenyls being injected. Analysis of functional pairs of glutathione-dependent enzymes revealed a certain imbalance in the antioxidant system function after aminobiphenyl poisoning.

Dimethoxybenzidine (DMO) and dimethylbenzidine (DM) are used to synthesize dyes such as C.I. Direct Blue 15 and C.I. Acid Red 114, respectively. These commercially used dyes are metabolically degraded to DMO or DM in the intestinal tract of rodents and subsequently DMO and DM are absorbed into the blood stream. Animals were exposed to DMO, DM, or the dyes in the drinking water. Tumors obtained from control and chemical-treated animals were examined for the presence of activated oncogenes by the NIH 3T3 DNA transfection assay. Activated oncogenes were detected in less than 3% (1/38) of the tumors from control animals whereas 68% (34/50) of the tumors from chemical-treated animals contained detectable oncogenes. Activated oncogenes were detected in both malignant (25/36) and benign (9/14) tumors from the chemically treated animals but only in one of 13 malignant tumors from the control animals. The presence of oncogenes in the chemically induced benign tumors suggests that oncogene activation was an early event in those tumors. Southern blot analysis of transfectant DNA showed that the transforming properties of the chemically induced rat tumor DNAs were due to the transfer of an activated H-ras (31/34) or N-ras (3/34) gene. One spontaneous rat tumor DNA was found to contain an activated H-ras gene. Oligonucleotide hybridization analysis indicated that the H-ras oncogenes from chemical-associated tumors contained mutations at codons 12, 13, or 61 whereas the spontaneously activated H-ras gene contained a point mutation at codon 61. These data suggest that activation of cellular ras genes by point mutation is an important step in the induction of tumors, at least in rats, by this class of benzidine-derived dyes. Moreover, in light of common histogenesis of the normal counterparts of many of the chemically induced neoplasms and histological evidence of varied tissue differentiation in some basal cell neoplasms, it is possible that most or all of the chemically induced neoplasms were derived from a common epidermal progenitor stem cell population.

In aqueous solution peroxidase catalyzes the conversion of o-tolidine to tolidine blue by hydrogen peroxide. This reaction of practical significance for analytical tests was studied by optical and ESR spectroscopy. For the blue dye formed in aqueous solution a meriquinoidic structure was proposed which is in equilibrium with an instable radical compound. This equilibrium is shifted to higher radical concentrations by ethylene glycol. Naphthene derivatives stabilize the meriquinoidic structure by means of non-covalent interactions resulting in a decrease of the radical concentration. In crosslinked gelatin the dye formation runs analogously, so that this system is suitable for providing evidence for H2O2-forming reactions. Naphthene derivatives substituted by sufficiently long aliphatic groups are diffusion stable in crosslinked gelatin. By interacting with the dye they prevent its rapid chemical decomposition and diffusion into the sample solution. It was shown, furthermore, that by means of such systems with a suitable structure of the layers both substrates and enzymes participating in the reaction may be determined analytically. This does provide a basis for developing new analytical test variants.

Covalent binding of benzidine and some congeners to hemoglobin was studied in female Wistar rats after oral administration. Hemoglobin adducts were hydrolyzed under alkaline conditions, and the arylamines analyzed by high performance liquid chromatography. With benzidine, three cleavage products were observed, the major component being monoacetylbenzidine. This indicates that 4-nitroso-4'-N- acetylaminobiphenyl is the major reactive metabolite in erythrocytes. In addition benzidine and 4-aminobiphenyl were identified. With 3,3'-dichlorobenzidine dihydrochloride, 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine two cleavage products were observed, the parent diamines being present in excess to or in amounts comparable to the monoacetyl derivative. With 3,3',5,5'-tetramethylbenzidine a hemoglobin adduct could not be found. When the azo dye direct red 28 was administered to the animals, the three cleavage products typical for benzidine were found, indicating that benzidine became bioavailable after reductive cleavage of the azo compound. In this case the fraction of 4-aminobiphenyl was greater than after benzidine. It is proposed to use the analysis of hemoglobin adducts in human blood to control the exposure of individuals to these carcinogenic chemicals in the course of biochemical effect monitoring.

Metabolism studies were conducted in the rat with Direct Red 2, based on 3,3'-dimethylbenzidine. The metabolism of Direct Red 2 compared with its base, dimethylbenzidine, indicated that the base was more extensively metabolized, yet only a small percentage of the (14)C in extracts was identified as known metabolites.

Several studies demonstrated that hamster hepatocytes are more effective than rat hepatocytes in mediating the metabolic activation of certain chemicals to their genotoxic (ie, mutagenic) derivatives. A comparison of the amount of deoxyribonucleic acid repair induced in rat and hamster hepatocytes by 7 azo dyes and 17 aromatic amine azo reduction products of the dyes was performed using the primary hepatocyte culture/deoxyribonucleic acid repair assay. Congo Red & its azo reduction product, benzidine, were more potent inducers of deoxyribonucleic acid repair in hamster than in rat hepatocytes, whereas Trypan Blue and its reduction product, o-tolidine, were equipotent in the 2 hepatocyte systems. Evans Blue, another o-Tolidine-based dye, elicited a greater deoxyribonucleic acid repair response in hamster hepatocytes. The absolute potency of these dyes, however, was much less than their reduction products. These findings extend previous observations of the superior metabolic activation capabilities of hamster, relative to rat hepatocytes.

Direct Red 2 was given as an aqueous solution to rats and hamsters to determine whether the dye is cleaved to potentially carcinogenic aromatic amines. The urine from treated animals revealed appreciable levels of 3,3'-dimethylbenzidine, mono- and di-acetyldimethylbenzidine, and alkaline hydrolyzable conjugates. Peak concns of the metabolites in urine occurred 12-24 hr after admin to rats, and within 12 hr in hamsters. The levels of all metabolites and conjugates diminished rapidly in both species after peak concentrations were reached, with no residues detected after 96 hr. The results demonstrated in vivo cleavage of the dye in both species.

For more Metabolism/Metabolites (Complete) data for 3,3'-DIMETHYLBENZIDINE (16 total), please visit the HSDB record page.

... Absorption of /o-Tolidine/ has occured via inhalation, incidental ingestion, and percutaneous penetration.

o-Tolidine is rapidly absorbed through intact human skin. ... Absorption also occurs from the respiratory at GI tract, at excretion of the parent compound at its mutagenic metabolites occurs primarily via the urine.

3,3'-Dimethylbenzidine is used as an intermediate for the production of dyes and pigments.

Used as an intermediate in the production of dyes and pigments; used as a curing agent for polyurethane elastomers, coatings, and rigid foams; [HSDB]

Plastic Composites Manufacturing [Category: Industry]

Manufacture of dyes; also as very sensitive reagent for gold (1:10 million detectable); and for free chlorine in water.

Intermediate in the production of the azo dyes Direct Red 2 and Acid Red 114

... Curing agent for urethane resins.

(1974) 2.73X10+8 g

(1983) 75,307 lb

(1979) 3.5 million lbs.

Reduction of Ortho-nitrotoluene to 1,2-diorthotolylhydrazine and subsequent rearrangement with acid

Reduction of o-nitrotoluene with zinc dust and caustic soda and conversion of the hydrazotoluene by boiling with hydrochloric acid.

Made by alkaline reduction of o-nitrotoluene with zinc, and subsequent rearrangement of the o-hydrazotoluene formed, by boiling with HCl.

Grades: technical, dry or paste.

o-Tolidine is marketed as the free base and as the dihydrochloride. Both are supplied as moist products with a water content of 10-30%.

[1,1'-Biphenyl]-4,4'-diamine, 3,3'-dimethyl-: ACTIVE

An important derivative of o-tolidine is its diacetoacetyl compound, 4,40-bisacetoacetylamino-3,30-dimethyl diphenyl, which is marketed under the trade name Naphtol AS-G; it is a coupling agent which is frequently used and in combination with chloroanilines gives yellow shades; o-Tolidinediisocyanate is employed as a cross-linking agent to make polymers.