3,3'-Dimethoxybenzidine-4,4'-diisocyanate

less than 1 mg/mL at 63.5 °F (NTP, 1992)

Soluble in ketones and esters

234 °F (NTP, 1992)

112 °C min

3,3'-dimethoxybenzidine-4,4'-diisocyanate appears as gray to brown powder or dark beige sandy powder. Melting point 112 °C. Insoluble in water. Toxic by inhalation and ingestion. A skin irritant. Used in making plastics.

Gray to brown solid; [HSDB] May decompose upon exposure to light and air; [MSDSonline]

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P261, P262, P264, P270, P271, P280, P301+P316, P302+P352, P304+P340, P316, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 39 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

A respiratory and mucous membrane irritant; Diisocyanates are known to cause occupational asthma; Some cause skin sensitization; [CHEMINFO] A severe irritant; A lachrymator and potential sensitizer; Inhalation my result in edema; [MSDSonline] See DIISOCYANATES.

3,3'-Dimethoxybenzidine-4,4'-diisocyanate; IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Some Chemicals Used in Plastics and Elastomers, International Agency for Research on Cancer, 39: 279-86 (1986). The human carcinogenic risk posed by exposure to 3,3'-dimethoxybenzidine-4,4'-diisocyanate.

Bioassay of 3,3'-Dimethoxybenzidine-4,4'-diisocyanate for Possible Carcinogenicity (1979) Technical Rpt Series No. 128 DHEW Pub No. (NIH) 79-1383, U.S. Department of Health Education and Welfare, National Cancer Institute, Bethesda, MD 20014

3,3'-DIMETHOXYBENZIDINE-4,4'-DIISOCYANATE may react with amines, aldehydes, alcohols, alkali metals, ketones, mercaptans, strong oxidizing agents, hydrides, phenols, and peroxides with vigorous releases of heat. May undergo polymerization reactions with acids and bases.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If 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.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves.

Vapor Concentration: 0.2 ppm or less: Any supplied-air respirator or any self-contained breathing apparatus. 1 ppm or less: Any supplied-air respirator with a full facepiece, helmet, or hood or any self-contained breathing apparatus with a full facepiece. A type C supplied air respirator operated in a pressure-demand or other positive pressure or continuous flow mode. 20 ppm or less: A type C supplied-air respirator with a full facepiece operated in pressure-demand or other positive pressure mode or with a full facepiece, helmet, or hood operated in continuous-flow mode. Greater than 20 ppm or entry and escape from unknown concentrations: Self-contained breathing apparatus with a full facepiece operated in a pressure-demand or other positive pressure mode or a combination respirator which includes a type C supplied-air respirator with a full facepiece operated in pressure-demand or other positive pressure or continuous-flow mode and an auxiliary self-contained breathing apparatus operated in pressure-demand or other positive pressure mode. Escape: Any escape self-contained breathing apparatus. /Methyl isocyanate/

Antidotes to cyanide poisoning include hydroxocobalamin and sodium nitrite, which release the cyanide from the cytochrome system, and rhodanase, which is an enzyme occurring naturally in mammals that combines serum cyanide with thiosulfate, producing comparatively harmless thiocyanate. Oxygen therapy can also be administered. (L97)

Exposure to high levels of cyanide for a short time harms the brain and heart and can even cause coma, seizures, apnea, cardiac arrest and death. Chronic inhalation of cyanide causes breathing difficulties, chest pain, vomiting, blood changes, headaches, and enlargement of the thyroid gland. Skin contact with cyanide salts can irritate and produce sores. (L96, L97)

IDENTIFICATION AND USE: This chemical is a gray to brown powder which is soluble in ketones and esters. It is used in polymers and adhesive systems, as a high strength backbone or cross linking intermediate. HUMAN EXPOSURE AND TOXICITY: Isocyanates are irritating to the skin and the mucous membranes, Skin conditions range from localized itching to wide spread eczema. Eye affections are less common and lacrimation is often found, conjunctivitis is rare. Respiratory system effects can be severe. ANIMAL STUDIES: Limited evidence of carcinogenicity in animals. Groups of male and female B6C3F1 mice, six weeks old were given dietary concentrations of this chemical for 78 weeks followed by a basal diet for a further 25 weeks. There was no significant difference in treated and control animals. There was no increased incidence of tumors in treated animals. Groups of male and female Fischer 344/N rats, six weeks of age received the chemical by gavage for 22 weeks. Animals were subsequently fed a basal diet for 22 weeks. A significant increase in combined incidence of leukemias and malignant lymphomas was observed. Increased incidence of various skin tumors was also noted on the head, back and inguinal areas in males and females. Increased incidences of Zymbal gland tumors was observed. Levels of Evidence of Carcinogenicity: Male Rats: Positive; Female Rats: Positive; Male Mice: Negative; Female Mice: Negative.

Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)

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. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=91-93-0]

Isocyanates are irritating to the skin and the mucous membranes, the skin conditions ranging from localized itching to more or less widespread eczema. Eye affections are less common and, although lacrimation is often found, conjunctivitis is rare. The commonest and most serious troubles, however, are those affecting the respiratory systems. /Isocyanates/

3,3'-Dimethoxybenzidine-4,4'-diisocyanate

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 39: (1986) Some Chemicals Used in Plastics and Elastomers

1987

1987

3,3'-Dimethoxybenzidine-4,4'-diisocyanate

Groups of 50 male and 50 female B6C3F1 mice, six weeks old, were given dietary concentrations of 22,000 or 44,000 mg/kg 3,3'-dimethoxybenzidine-4,4'-diisocyanate (purity unspecified, but containing at least two impurities) ad libitum for 78 weeks, followed by basal diet for a further 25 weeks, at which time all animals were killed. Diets were prepared daily and a check of stability in the diet showed no decomposition. Groups of 20 male and 20 female mice receiving basal diet only for 103 weeks served as controls. There was no significant difference in survival of treated and control animals: 18/20 (90%) control, 40/50 (80%) low dose and 46/50 (92%) high dose males; 18/20 (90%) control, 36/50 (72%) low dose and 31/50 (62%) high dose females survived to the end of the experiment. There was no increased incidence of treatment related tumors.

Rat: Groups of 50 male and 50 female Fischer 344/N rats, six weeks of age, received 1500 or 3000 mg/kg bw 3,3'-dimethoxybenzidine-4,4'-diisocyanate ... /purity unspecified, but containing at least two impurities/ as a 15-30% aqueous suspension containing 9 g sodium chloride, 5 g carboxymethylcellulose, 4 ml polysorbate 80 and 9 mg benzyl alcohol/l, by gavage on five days per week for 22 weeks. Animals were subsequently fed diets containing concentrations of 22 000 or 44 000 mg/kg 3,3'-dimethoxybenzidine-4,4'-diisocyanate for a further 56 weeks and were then kept on basal diet and observed for a further 26 weeks prior to sacrifice. Control groups of 20 male and 20 female rats received the suspending vehicle alone for 22 weeks followed by 82 weeks of basal diet. Survival of both male and female rats at termination of the study (104 weeks) was dose related: 15/20 (75%) control, 22/50 (44%) low dose and 16/50 (32%) high dose males; 15/20 (75%) control, 21/50 (42%) low dose and 21/50 (42%) high dose females. A significant increase in the combined incidence of leukemias and malignant lymphomas was observed: 0/18 control, 18/48 low dose and 16/46 high dose males (p= 0.022, trend test; p= 0.001 (low dose) and p= 0.002 (high dose), Fisher exact test); 1/20 control, 8/50 low dose and 15/48 high dose females (p= 0.007, trend test; p= 0.016 (high dose) Fisher exact test). Increased incidences of various types of skin tumors were observed on the head, back and inguinal areas in males and females. This increase was statistically significant in both high dose (14/46; p= 0.005, Fisher exact test) and low dose (17/48; p= 0.002, Fisher exact test) males as compared to controls (0/18). A treatment related increase in the incidence of Zymbal gland tumors was observed: 1/18 control, 6/48 low dose and 9/46 high dose males; 0/20 control, 9/50 low dose and 6/48 high dose females. The historical incidence of these neoplasms in untreated Fischer 344/N rats from the same laboratory was 1/300 males and 0/298 females. A dose related incidence of endometrial stromal polyps was observed in females: 0/20 control, 5/48 low dose and 10/48 high dose animals (p= 0.013, trend test; p= 0.022 (high dose), Fisher exact test). (The Working Group noted the limited biological significance attached to these lesions by the authors.)

Levels of Evidence of Carcinogenicity: Male Rats: Positive; Female Rats: Positive; Male Mice: Negative; Female Mice: Negative.

Noncardiogenic pulmonary edema and bronchospasm are the most immediate serious clinical consequences of isocyanate exposure. Markedly symptomatic patients should receive oxygen, ventilatory support, and an intravenous line. Treatment for asthma includes inhaled sympathomimetics (salbutamol, metaproterenol), intravenous theophylline, parenteral sympathomimetics (epinephrine, terbutaline), and steroids. /Isocyanates/

Most treatment is symptomatic. Mydriatics, systemic analgesics, and topical antibiotics (Sulamyd) may be used for corneal abrasions. There is no effective therapy for sensitized workers, and these people should be moved to a work site devoid of exposure to isocyanates. /Isocyanates/

Cyanide is rapidly alsorbed through oral, inhalation, and dermal routes and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96)

Used in polymers and adhesives; [HSDB]

Working with Glues and Adhesives [Category: Other]

Polymers and adhesive systems, high strength backbone or cross-linking intermediate.

(1977) NOT PRODUCED COMMERCIALLY IN US

(1979) NOT PRODUCED COMMERCIALLY IN US