3,3'-Dimethoxy-benzidin

Hazardous Air Pollutants (HAPs)

Carcinogens

log Kow = 1.81

1.81

1.81

LEAFLETS OR NEEDLES FROM WATER

Colorless crystals that turn a violet color on standing.

less than 0.1 mg/mL at 68 °F (NTP, 1992)

Sol in alc, benzene, ether

Sol in chloroform, acetone

PROBABLY SOL IN MOST ORG SOLVENTS AND LIPIDS

In water, 60 mg/l @ 25 °C

Solubility in water, g/100ml at 25 °C: 0.006

403 °F (NTP, 1992)

206 °C

206 °C (403 °F) (closed cup)

206 °C c.c.

403 °F

403 °F

279 to 280 °F (NTP, 1992)

137 °C

137.5 °C

279 °F

137 °C

279 °F

8.5 (NTP, 1992) - Heavier than air; will sink (Relative to Air)

8.43 (air= 1)

8.5

Danger

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

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

Danger

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

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

Chemical: [1,1'-Biphenyl]-4,4'-diamine, 3,3'-dimethoxy-

Hazard Traits - Carcinogenicity

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.)

This chemical is combustible. (NTP, 1992)

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

3,3'-Dimethoxybenzidine is used as an intermediate in the production of dyes and pigments. No information is available on the acute (short-term), chronic (long-term), reproductive, developmental, or carcinogenic effects of 3,3'-dimethoxybenzidine in humans. Animal studies have reported effects on the liver, kidneys, spleen, and bladder, and endocrine effects, gastritis, intestinal hemorrhage, and weight loss from chronic oral exposure. Increased incidences of tumors in several organs have been reported in rats orally exposed to 3,3'-dimethoxybenzidine or its salt. EPA has classified 3,3'-dimethoxybenzidine as a Group B2, probable human carcinogen.

Causes liver injury and tumors in experimental animals; [HSDB] No published epidemiology studies on dye workers and cancer; Currently, dye production in closed systems with low risk to workers; [NTP] Classified by NIOSH as a carcinogen--reduce exposure to lowest feasible concentration; [NIOSH] Symptoms: Irritation skin; [CAMEO]

USEPA/ECAO; Health and Environmental Effects Profile for 3,3'-Dimethoxybenzidine (1987) EPA/600/X-87/101, NTIS No. PB89-119515

DHHS/NTP; Toxicology & Carcinogenesis Studies of 3,3'-Dimethoxybenzidine dihydrochloride in F344/N Rats (Drinking Water Studies) Technical Report Series No. 372 (1990) NIH Publication No. 90-2827

National Toxicology Program. Eleventh Report on Carcinogens (2005). 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'-Dimethoxybenzidine (119-90-4) is listed as reasonably anticipated to be a human carcinogen. /3,3'-Dimethoxylbenzidine and Dyes Metabolized to 3,3'-Dimethoxylbenzidine/[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s073dmob.pdf]

U091; As stipulated in 40 CFR 261.33, when 3,3'-dimethoxybenzidine, 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 container or inner liner used to hold this waste or 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(e)).

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

Use water spray, 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. 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.

(General first aid procedures)

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

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 U091, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A good candidate for liquid injection incineration at a temperature range of 650 to 1,600 °C and a residence time of 0.1 to 2 seconds. 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.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

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

For more Disposal Methods (Complete) data for 3,3'-DIMETHOXYBENZIDINE (7 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'-DIMETHOXYBENZIDINE (13 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 230(SRC), determined from a log Kow of 1.81(2) and a regression-derived equation(3), indicates that 3,3'-dimethoxybenzidine is expected to have moderate mobility in soil(SRC). The first pKa of 3,3'-dimethoxybenzidine is estimated as 4.2(SRC), using an estimation method based on perturbed molecular orbital theory and linear free energy (LFER) methods(4). This estimated pKa indicates that 3,3'-dimethoxybenzidine will partially exist in the protonated form under acidic conditions and cations have greater adsorption to soils than neutral molecules(SRC). Furthermore, 3,3'-dimethoxybenzidine is an aromatic amine which may form covalent bonds with humic materials resulting in relatively immobile quinone-like complexes(5). Volatilization of the neutral species of 3,3'-dimethoxybenzidine from moist soil surfaces is not expected to be an important fate process(SRC) based upon an estimated Henry's Law constant of 4.7X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(6). The conjugate acid of 3,3-dimethoxybenzidine will not volatilize since cations are non-volatile(SRC). 3,3'-Dimethoxybenzidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-7 mm Hg(SRC), determined from a fragment constant method(7). No data were found regarding the biodegradation of 3,3'-dimethoxybenzidine in soils; however, screening studies using sewage sludge inoculum suggest biodegradation will occur slowly in the environment(8,9). Structurally similar compounds such as benzidine are shown to be rapidly oxidized by Fe(III) and other cations which are frequently found in soil(10), which suggest that 3,3'-dimethoxybenzidine may also be degraded by a similar process(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 230(SRC), determined from a log Kow of 1.81(2) and a regression-derived equation(3), indicates that 3,3'-dimethoxybenzidine is expected to adsorb to suspended solids and sediment(SRC). The frist pKa of 3,3'-dimethoxybenzidine is estimated as 4.2(SRC), using an estimation method based on perturbed molecular orbital theory and linear free energy (LFER) methods(4). This estimated pKa indicates that 3,3'-dimethoxybenzidine will partially exist in the protonated form under acidic conditions and cations have greater adsorption to suspended solids and sediment than neutral molecules(SRC). Volatilization of the free base from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 4.7X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). The conjugate acid of 3,3'-dimethoxybenzidine will not volatilize since cations are non-volatile(SRC). According to a classification scheme(6), an estimated BCF of 5(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). No information on the biodegradation of 3,3'-dimethoxybenzidine in natural waters was found(SRC), but this compound was reported to be resistant to biodegradation in the Japanese MITI test(8), suggesting biodegradation in waters will most likely occur slowly(SRC). Structurally similar compounds such as benzidine are shown to be rapidly oxidized by Fe(III) and other cations which are frequently found in environmental waters(9), which suggest that 3,3'-dimethoxybenzidine may also be degraded by a similar process(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 3,3'-dimethoxybenzidine, which has an estimated vapor pressure of 1.2X10-7 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'-dimethoxybenzidine 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 3 hours(SRC), calculated from its rate constant of 1.3X10-10 cu cm/molecule-sec at 25 °C (SRC)determined using a structure estimation method(3). Since 3,3'-dimethoxybenzidine absorbs light greater than 290 nm(4), it may be susceptible to direct photolysis in the environment(SRC). Particulate-phase 3,3'-dimethoxybenzidine may be removed from the air by wet and dry deposition(SRC).

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

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

Cough.

Redness.

irritation skin; In Animals: kidney, liver damage; thyroid, spleen changes; [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. /3,3'-Dimethoxybenzidine dihydrochloride/ [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=20325-40-0]

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/

The Koc of 3,3'-dimethoxybenzidine is estimated as 230(SRC), using a measured log Kow of 1.81(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that 3,3'-dimethoxybenzidine is expected to have moderate mobility in soil(SRC). The first pKa of 3,3'-dimethoxybenzidine is estimated as 4.2(SRC), using an estimation method based on perturbed molecular orbital theory and linear free energy (LFER) methods(4). This estimated pKa indicates that 3,3'-dimethoxybenzidine will partially exist in the protonated form under acidic conditions and cations have greater adsorption to soils than neutral molecules(SRC). Furthermore, 3,3'-dimethoxybenzidine is an aromatic amine which may form covalent bonds with humic materials resulting in relatively immobile quinone-like complexes(5).

NO EPIDEMIOLOGICAL DATA ON OCCURRENCE OF CANCER IN WORKERS EXPOSED TO O-DIANISIDINE ALONE APPEAR IN LITERATURE. MOST WORKERS EXPOSED ... HAVE ALSO BEEN EXPOSED TO RELATED AMINES SUCH AS BENZIDINE, WHICH HAS BEEN STRONGLY ASSOCIATED WITH OCCURRENCE OF URINARY BLADDER CANCER IN MAN.

3,3'-Dimethoxybenzidine's production and use as a chemical intermediate in the production of azo dyes(1) may result in its release to the environment through various waste streams(SRC). 3,3'-Dimethoxybenzidine is apparently not produced in the US any longer but may still be imported into the country(1).

3,3'-Dimethoxybenzidine was reported to be resistant to biodegradation in the Japanese MITI test(1). At low levels of yeast extract, 3,3'-dimethyoxybenzidine showed no consistent degradation in an OECD AFNOR sewage die-away test and it was not classified as readily biodegradable; only high levels of yeast extract (100-200 mg/l) enchanced the biodegradation of this compound(2). 3,3'-Dimethyoxybenzidine at 35 °C and an initial concn of 100 mg/l in the presence of an anaerobic sludge inoculum degraded 100% in 42 days(3).

U091; As stipulated in 40 CFR 261.33, when 3,3'-dimethoxybenzidine, 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 container or inner liner used to hold this waste or 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(e)).

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'-Dimethoxybenzidine 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 100 lb or 45.4 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

BISAZOBIPHENYL DYE DERIVED FROM 3,3'-DIMETHOXYBENZIDINE WAS METABOLIZED TO 3,3'-DIMETHOXYBENZIDINE IN BOTH THE DOG AND RAT. THE N-ACETYL DERIV OF 3,3'-DIMETHOXYBENZIDINE WAS IDENTIFIED IN URINE FROM RATS TREATED WITH DYE DERIVED FROM 3,3'-DIMETHOXYBENZIDINE.

... AFTER ADMIN OF A DOSE OF 1 G O-DIANISIDINE TO 2 DOGS, 0.4% FREE DIAMINE & ... 5% OF A METABOLITE WITH PROPERTIES SIMILAR TO ... 3,3'-DIHYDROXYBENZIDINE WERE EXCRETED IN URINE.

The carcinogenic aromatic amine 3,3'-dimethoxybenzidine was rapidly metabolized in the rat. GC/MS studies of urine and bile demonstrated the presence of 8 previously unidentified metabolites formed via-N-acetylation, hydroxylation, O-demethylation, and glucuronidation.

The conventional Ames assay metabolising system was confirmed to be deficient in its ability to N-acetylate. This may render the test less sensitive to compounds which normally have an acetylation step during their in vivo activation to carcinogens. The addition of acetyl-coenzyme A to the S9 mix in the Ames assay increased the mutagenicity of benzidine in Salmonella typhimurium strains TA98 and TA1538 4-5-fold. This was consistent with the observation that benzidine is N-acetylated prior to deoxyribonucleic acid binding in vivo in rat liver. Two 3,3'-disubstituted benzidines, o-tolidine and o-dianisidine, were also tested. A smaller increase in o-tolidine mutagenicity, compared to that observed with benzidine, occurred with the addition of acetyl-coenzyme A. However, the production of acetylated metabolites from o-tolidine was only 37% of that from benzidine. The mutagenicity of o-dianisidine was unaffected by acetyl-coenzyme A. Acetylation of o-dianisidine was only 16% of that observed with benzidine, and the N-acetyl derivatives of o-dianisidine showed lower mutagenicity than the parent amine.

For more Metabolism/Metabolites (Complete) data for 3,3'-DIMETHOXYBENZIDINE (12 total), please visit the HSDB record page.

O-DIANISIDINE HAS BEEN FOUND IN URINE OF WORKERS EXPOSED TO THIS CMPD.

(14)C-labeled 3,3'-dimethoxybenzidine was absorbed through rat skin after application of an acetone soln, and only 29% had disappeared from the application site in 24 hr. It was found in the tissues and excreta.

The carcinogenic aromatic amine 3,3'-dimethoxybenzidine was rapidly metabolized in the rat. Thirty min after iv admin of (14)C-3,3'-dimethoxybenzidine less than 2% of the dose could be recovered from the animal as the parent cmpd. Extensive biliary excretion (70%) resulted in the accumulation of 50% in the intestinal tract. Three days after either oral or iv dosing, 50% of the admin radiolabel had been excreted in the feces and 30-40% excreted in the urine while 45% of the remaining radiolabel was present in the liver in the form of covalently bound metabolites.

... In 1954 /results from laboratory tests indicated/ that skin is principal portal of entry of benzidines. ... It was considered likely that the hydrochloride salt could be absorbed percutaneously. /Benzidines/

For more Absorption, Distribution and Excretion (Complete) data for 3,3'-DIMETHOXYBENZIDINE (6 total), please visit the HSDB record page.

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

Used as a chemical intermediate in the production of dyes and dianisidine diisocyanate; Also used to dye leather, paper, plastics, rubber, and textiles; [HSDB]

Pulp and Paper Processing [Category: Industry]

CHEMICAL INTERMEDIATE IN PRODN OF O-DIANISIDINE DIISOCYANATE ... ; FOR DETECTION OF PRESENCE OF THIOCYANATES, NITRITES & A NUMBER OF METALS.

USED IN DYEING LEATHER, PAPER, PLASTIC, RUBBER, TEXTILES

CHEM INT FOR PIGMENTS, EG, PIGMENT ORANGE 16; DYE FOR ACETATE RAYON (FORMER USE)

(1984) 106,005 lb

(1983) 655,000 lb

(1977) 55,500 lb

(1971) 273,000 lb

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

3,3'-Dimethoxybenzidine is apparently not produced in the US any longer but may still be imported into the country.