Triaziquone

231.25052

231.25

200-692-6

F3D5D9P25I

29215

3249

DTXSID1021370

C903

Purple needles crystals from ethyl acetate

L - Antineoplastic and immunomodulating agents

43.2

-0.13

Triaziquone appears as purple needle-like crystals. (NTP, 1992)

1.727g/cm3

162.5-163 °C

357.5 °C

175.1ºC

1.846

In water, 1.1X10+5 mg/L at 25 deg C /Estimated/

3.4X10-6 mm Hg at 25 deg C /Estimated/

Henry's Law constant = 9.3X10-16 atm cu m/mol at 25 °C /Estimated/

pKa = 1.6 /Estimated/

Hydroxyl radical reaction rate constant = 3.1X10-11 cu cm/molec-sec at 25 °C /Estimated/

Slightly soluble in water.

Amines, Phosphines, and Pyridines

TRIAZIQUONE is an amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.

II

6.1(a)

3249

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

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

Excerpt from ERG Guide 151 [Substances - Toxic (Non-combustible)]: SMALL FIRE: Dry chemical, CO2 or water spray. LARGE FIRE: Water spray, fog or regular foam. Move containers from fire area if you can do it without risk. Dike fire-control water for later disposal; do not scatter the material. Use water spray or fog; do not use straight streams. FIRE INVOLVING TANKS OR CAR/TRAILER LOADS: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in fire. For massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and let fire burn. (ERG, 2016)

Excerpt from ERG Guide 151 [Substances - Toxic (Non-combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: You should dampen the solid spill material with acetone, then 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 adsorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

LD50 Rat iv 500 ug/kg|LD50 Rat ip 500 ug/kg

Triaziquone is not known to occur in nature(1).

Triaziquone's production and use as a research chemical and antineoplastic agent(1) may result in its release to the environment through various waste streams(SRC). Triaziquone was not produced commercially in the US (as of 1975); it has been produced for research purposes and was manufactured in West Germany(2).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a log Kow of -0.13(2) and a regression-derived equation(3), indicates that triaziquone is expected to have very high mobility in soil(SRC). Volatilization of triaziquone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.3X10-16 atm-cu m/mole(SRC), obtained using a fragment constant estimation method(4). Triaziquone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.4X10-6 mm Hg(SRC), determined from a fragment constant method(5).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a log Kow of -0.13(2) and a regression-derived equation(3), indicates that triaziquone is not 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 9.3X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3.2(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Hydrolysis may be an important environmental fate process since triaziquone contains aziridine groups(SRC); aziridine has a hydrolysis half-life of 154 days at pH 7 and 25 °C(7).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), triaziquone, which has an estimated vapor pressure of 3.4X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase triaziquone 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 13 hours(SRC), calculated from its rate constant of 3.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). The rate constant for the vapor-phase reaction of triaziquone with ozone has been estimated as 3.5X10-18 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(4). This corresponds to an atmospheric half-life of about 3.3 days at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(5). Particulate-phase triaziquone may be removed from the air by wet and dry deposition(SRC).

The rate constant for the vapor-phase reaction of triaziquone with photochemically-produced hydroxyl radicals has been estimated as 3.1X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 13 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of triaziquone with ozone has been estimated as 3.5X10-18 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). This corresponds to an atmospheric half-life of about 3.3 days at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(4). Hydrolysis may be an important environmental fate process since triaziquone contains aziridine groups(SRC); aziridine has a hydrolysis half-life of 154 days at pH 7 and 25 °C(5).

An estimated BCF of 3.2 was calculated for triaziquone(SRC), using a log Kow of -0.13(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of triaziquone is estimated as 20(SRC), using a log Kow of -0.13(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that triaziquone is expected to have very high mobility in soil.

The Henry's Law constant for triaziquone is estimated as 9.3X10-16 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that triaziquone is expected to be essentially nonvolatile from water surfaces(2). Triaziquone's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected(SRC). Triaziquone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.4X10-6 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to triaziquone may occur through inhalation and dermal contact with this compound at workplaces where triaziquone is produced or used(SRC). However, exposure may be limited(SRC), since triaziquone was not produced commercially in the US (as of 1975); it has been produced for research purposes and was manufactured in West Germany(1). Exposure would be expected to be limited to individuals receiving triaziquone as drug for cancer treatment(SRC).

Antineoplastic

A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026) (See all compounds classified as Antineoplastic Agents, Alkylating.)

... Hepatocyte cytotoxicity induced by trenimon (250 microM) under aerobic conditions ensued following an initial induction of cyanide-resistant respiration and partial oxidation of glutathione to oxidized glutathione. Trenimon reduction to the hydroquinone by the hepatocytes was rapid. Inhibition of hepatocyte DT-diaphorase by dicumarol increased trenimon-induced cytotoxicity by approximately 10-fold, and markedly inhibited hydroquinone formation. Both cyanide-resistant respiration and oxidized glutathione formation were markedly increased, resulting in depletion of oxygen in the media. Trenimon reduction to the hydroquinone then occurred. ... Hepatocyte cytotoxicity induced by trenimon (350 microM) under hypoxic conditions ensued following glutathione depletion without oxidized glutathione formation. Inactivation of hepatocyte DT-diaphorase by dicumarol under hypoxic conditions increased trenimon-induced cytotoxicity by approximately 3.5-fold and increased semiquinone radical levels 2-fold without affecting its reduction rate.|L5178Y/HBM10 lymphoblasts, resistant to hydrolyzed benzoquinone mustard, were approximately 2-fold more sensitive to trenimon (2,3,5-tris-ethyleneimino-1,4-benzoquinone) compared to parental cells (L5178Y). The L5178Y/HBM10 cells are reported to have a 24-fold increased level of DT-diaphorase activity over the parental cells. Inhibition of DT-diaphorase by dicoumarol markedly inhibited the cytotoxic activity of trenimon to the resistant L5178Y/HBM10 cells. Spectrophotometric analysis of the reduction of the quinone, trenimon, to its hydroquinone form was shown to occur approximately 25 times more rapidly in the L5178Y/HBM10 cells relative to the parental cells and was inhibited by discoumarol. Trenimon also induced continuous cyanide-resistant respiration in the L5178Y cells, but not in the resistant L5178Y/HBM10 cells.|Treatment of Ehrlich ascites tumor cells with the alkylating agent triaziquone [2,3,5-tris(ethyleneimino)benzoquinone-1,4] and nitrogen mustard leads to a reduction of the posttranslational acetylation of histones. Acetylation of all core histones is affected. The reduction of labeling of acetylated sites is accompanied by a dose-dependent decrease in the extent of acetylation as indicated by the level of acetylation of H4. The depression of histone acetylation is expressed at all concentrations of the alkylating agents which cause significant inhibition of tumor cell proliferation.

Excerpt from ERG Guide 151 [Substances - Toxic (Non-combustible)]: Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution. (ERG, 2016)|Mutagens

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. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. 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: 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. Generally, the induction of vomiting is NOT recommended outside of a physician's care due to the risk of aspirating the chemical into the victim's lungs. However, if the victim is conscious and not convulsing and if medical help is not readily available, consider the risk of inducing vomiting because of the high toxicity of the chemical ingested. Ipecac syrup or salt water may be used in such an emergency. IMMEDIATELY transport the victim to a hospital. 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)

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . 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 normal saline 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 patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/CASE REPORTS/ Three patients, one with an adenocarcinoma of the colon with metastases to the lung, one with a mammary carcinoma with metastases to the lymph nodes and one with a squamous-cell carcinoma of the bronchus without metastases, were treated with triaziquone for 52, 17 and 42 months, respectively. In one case androgens were given also. Leucopenia was evident in all three cases, and at autopsy, 10 months to 4 and one-half years after the end of treatment, atypical reticulum-cell growths described as "neoplastic reticulosis" were found in the bone marrow, spleen and lymph nodes. Treatment of a myosarcoma with triaziquone for one and one-half years was associated with the later occurrence of a monocytic leukemia; a course of radiation had been given also.

2,3,5-Tris(ethyleneimine)benzoquinone

Triaziquone was not produced commercially in the US (as of 1975); it has been produced for research purposes and was manufactured in West Germany.

Health Hazards -> Mutagens