Triethylenetetramine

146.23

146.23

605448

203-950-6

SJ76Y07H5F

1123

443

2259

DTXSID9023702

MODERATELY VISCOUS, YELLOWISH LIQUID

A16AX|A - Alimentary tract and metabolism

29212900

76.1

-1.4/-1.66

Triethylenetetramine appears as a yellowish liquid. Less dense than water. Combustible, though may be difficult to ignite. Corrosive to metals and tissue. Vapors heavier than air. Toxic oxides of nitrogen produced during combustion. Used in detergents and in the synthesis of dyes, pharmaceuticals and other chemicals.

0.9818 g/cm³ @ Temp: 20 °C

12 °C

266-267 °C @ Press: 760 Torr

290 °F

n20/D 1.496(lit.)

H2O: soluble ;alcohol: soluble

Store below +30°C.

<0.01 mm Hg ( 20 °C)

~5 (vs air)

LD50 orally in rats: 2.5 g/kg (Spitz)

vol% in air: 1.1

STRONGLY BASIC (PH 10 IN 1% AQ SOLN)

CONVERSION UNITS: 1 MG/L= 167 PPM, 1 PPM= 5.98 MG/CU M|WT 8.2 LB/GAL @ 20 °C|CAN REACT WITH OXIDIZING MATERIALS

Soluble in water.

Amines, Phosphines, and Pyridines

TRIETHYLENETETRAMINE is a strong base; reacts violently with strong oxidants; attacks aluminum, zinc, copper and its alloys. Handling Chemicals Safely 198. p. 934).

640 °F (USCG, 1999)|640 °F.|335 °C

II

8

UN 2259 8/PG 2

2

21-34-43-52/53

26-36/37/39-45-61

YE6650000

C

Separated from food and feedstuffs. See Chemical Dangers. Cool. Store in an area without drain or sewer access. Provision to contain effluent from fire extinguishing.

Syable. Incompatible with strong oxidizing agents, strong acids.

P273-P280-P305 + P351 + P338-P310

H312-H314-H317-H412

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]: Combustible material: may burn but does not ignite readily. When heated, vapors may form explosive mixtures with air: indoors, outdoors and sewers explosion hazards. Those substances designated with a (P) may polymerize explosively when heated or involved in a fire. Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form. (ERG, 2016)|Combustible. Gives off irritating or toxic fumes (or gases) in a fire. Risk of fire and explosion on contact with oxidants. See Chemical Dangers.

|Danger|H312: Harmful in contact with skin [Warning Acute toxicity, dermal]|P260, P261, P264, P272, P273, P280, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P321, P322, P333+P313, P363, P405, and P501|H302+H312 (19.37%): Harmful if swallowed or in contact with skin [Warning Acute toxicity, oral; acute toxicity, dermal]|P260, P261, P264, P270, P272, P273, P280, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P321, P322, P330, P333+P313, P363, P405, and P501|Aggregated GHS information provided by 2363 companies from 21 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P260, P261, P264, P270, P271, P272, P273, P280, P284, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P320, P321, P322, P330, P333+P313, P363, P403+P233, P405, and P501|H311: Toxic in contact with skin [Danger Acute toxicity, dermal]|P260, P261, P264, P271, P272, P280, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P321, P322, P333+P313, P361, P363, P403+P233, P405, and P501

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (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)

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]: ELIMINATE all ignition sources (no smoking, flares, sparks or flames in immediate area). Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS. (ERG, 2016)

Amine-type canister; goggles or face shield; rubber gloves. (USCG, 1999)|B) PROTECT HANDS WITH RUBBER GLOVES &...BARRIER CREAMS. /ALIPHATIC AMINES/

SLIGHT, WHEN EXPOSED TO HEAT OR FLAME.

Explosive limits , vol% in air: 1.1-?

CARBON DIOXIDE, DRY CHEMICAL, ALCOHOL FOAM.

.../IT WAS/ CONCLUDED THAT CONTROL PROBLEM WAS PRIMARILY ONE OF PREVENTING DIRECT SKIN CONTACT. SUCCESSFUL CONTROL REQUIRES GOOD PERSONNEL TRAINING AND SCRUPULOUS HANDLING TECHNIQUES.|C) DECR CONCN OF AMINE VAPOR BY GOOD VENTILATION. AMINES WITH HEAVY VAPOR... SHOULD BE DRAWN OFF BY DESCENT. D) EMPLOYEES PRONE TO SENSITIZATION OR LIVER DEFICIENCY...REMOVED FROM SHOPS HANDLING HARDENERS. /ALIPHATIC AMINES/

/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Health: TOXIC; inhalation, ingestion, or skin contact with material may cause severe injury or death. Contact with molten substance may cause severe burns to skin and eyes. 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.|/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Fire or Explosion: Combustible material: may burn but does not ignite readily. When heated, vapors may form explosive mixtures with air: indoors, outdoors, and sewers explosion hazards. Those substances designated with a "P" may polymerize explosively when heated or involved in a fire. Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form.|/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Public Safety: CALL Emergency Response Telephone Number ... . 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. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. Ventilate enclosed areas.|/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible.|For more DOT Emergency Guidelines (Complete) data for TRIETHYLENETETRAMINE (8 total), please visit the HSDB record page.

No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./|The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.

Personal protection: chemical protection suit including self-contained breathing apparatus. Do NOT let this chemical enter the environment. Collect leaking liquid in sealable containers. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

Separated from food and feedstuffs. See Chemical Dangers. Cool. Store in an area without drain or sewer access. Provision to contain effluent from fire extinguishing.

No indication can be given about the rate at which a harmful concentration of this substance in the air is reached on evaporation at 20 °C.

The substance is corrosive to the eyes, skin and respiratory tract. Corrosive on ingestion. Inhalation may cause lung oedema, but only after initial corrosive effects on eyes and/or airways have become manifest.

Repeated or prolonged contact may cause skin sensitization. Repeated or prolonged inhalation may cause asthma.

NO open flames. NO contact with oxidizing agents.

PREVENT GENERATION OF MISTS! AVOID ALL CONTACT! IN ALL CASES CONSULT A DOCTOR!

Use ventilation, local exhaust or breathing protection.

Protective gloves. Protective clothing.

Wear face shield or eye protection in combination with breathing protection.

| 3 - Materials that, under emergency conditions, can cause serious or permanent injury.| 1 - Materials that must be preheated before ignition can occur. Materials require considerable preheating, under all ambient temperature conditions, before ignition and combustion can occur.| 0 - Materials that in themselves are normally stable, even under fire conditions.

Neurological worsening may be associated with TETA therapy. Trientine also chelates iron, and co-administration of trientine and iron should be avoided because the complex with iron is toxic. A reversible sideroblastic anemia may be a consequence of overtreatment and resultant copper deficiency. Lupus-like reactions have also been reported. The oral LD50 value in rats is rat, mouse, rabbit is 2500mg/kg, 1600mg/kg, and 5500mg/kg, respectively.

In clinical trials conducted in children with Wilson disease, serum aminotransferase levels generally improved or were stable during treatment with trientine. There have been no clinical reports of acute liver injury with jaundice attributed to trientine, even with overdoses. Patients with Wilson disease typically have mild-to-moderate serum aminotransferase elevations and may have signs and symptoms of cirrhosis. Improvement in liver injury in Wilson disease typically requires months to years of treatment.

EMPLOYEES PRONE TO SENSITIZATRION OR LIVER DEFICIENCY...REMOVED FROM SHOPS HANDLING HARDENERS. /ALIPHATIC AMINES/

Trientine is a copper chelator used in the treatment of Wilson's disease as an alternative to D-penicillamine. It tends to be used in patients who are experiencing serious adverse effects from penicillamine therapy or intolerance of penicillamine.|Cuprior is indicated for the treatment of Wilson's disease in adults, adolescents and children ≥ 5 years intolerant to D-penicillamine therapy.

Trientine is an oral copper chelating agent used to treat Wilson disease. Trientine has not been associated with worsening of serum enzyme elevations during therapy or with cases of clinically apparent liver injury with jaundice.

Chelating Agents

Antidotes; Chelating Agents; Indicators and Reagents|MEDICATION (VET): EXPTL USE: BASAL URINE COPPER EXCRETION BY RATS WAS INCR FROM 65.1 TO 357.1 OR 305.9 NMOL/24 HR BY TRIETHYLENETETRAMINE DIHYDROCHLORIDE (100 MG ORALLY).|MEDICATION (VET): EXPTL USE COPPER MOBILIZING EFFECT OF 16 SUBSTANCES WAS STUDIED IN RATS. TRIETHYLENETETRAMINE SHOWED MOST EFFICACY.|MEDICATION (VET): EXPTL USE 0.75 MMOL/KG WAS ADMIN IP TO RATS PRIOR TO ADMIN OF (63)NICL2. TRIETHYLENETETRAMINE (TETA) REDUCED PLASMA (63)NI CONCN & INCR URINE EXCRETION DURING 6 HR AFTER INJECTION OF (63)NICL2, COMPARED TO CONTROLS THAT RECEIVED ONLY (63)NICKEL CHLORIDE.|For more Therapeutic Uses (Complete) data for TRIETHYLENETETRAMINE (12 total), please visit the HSDB record page.

TETA is a selective copper (II) chelator. tightly binds and facilitates systemic elimination of Cu(II) into the urine whilst neutralizing its catalytic activity, but does not cause systemic copper deficiency even after prolonged use. It may also act as an antioxidant as it suppresses the copper-mediated oxidative stress. TETA not only increases urinary Cu excretion, but also decreases intestinal copper absorption by 80%.

Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS. (See all compounds classified as Chelating Agents.)

It is poorly absorbed from the gastrointestinal tract with a bioavailability of 8 to 30% and and what is absorbed is metabolized and inactivated. 5% to 18% that is systemically absorbed in humans is reported to be extensively metabolized. The time to reach peak concentration (Tmax) for humans occur between 0.8 to 4 hours.|The unchanged drug and two acetylated metabolites, N1-acetyltriethylenetetramine (MAT) and N1,N10-diacetyltriethylenetetramine (DAT), are mainly excreted in the urine. About 1% of the administered trientine and about 8% of the biotransformed trientine metabolite, acetyltrien, ultimately appear in the urine. The amounts of urinary copper, zinc and iron increase in parallel with the amount of trientine excreted in the urine. Unchanged drug is also excreted in feces after oral administration.|It is widely distributed in tissues with relatively high concentrations measured in liver, heart, and kidney. A recent study reported that the central and peripheral volumes of distribution were 393 L and 252 L, respectively.

It is mainly metabolized via acetylation, and two major acetylated metabolites exist in human serum and urine. TETA is readily acetylated into N1-acetyltriethylenetetramine (MAT) and N1,N10-diacetyltriethylenetetramine (DAT). MAT is still capable of binding divalent Cu, Fe, and Zn but to a much lesser extent compared to the unchanged drug. To date no enzyme has been definitely identified as responsible for TETA acetylation but spermidine/spermine acetyltransferase-1 (SSAT-1) is a potential candidate responsible for acetylation of TETA because of the close chemical resemblance between its natural substrate spermidine and TETA. TETA is also shown to be a substrate for human thialysine acetyltransferase (SSAT2) in vitro.

The plasma elimination half life of TETA in healthy volunteers and Wilson's disease patients ranges from 1.3 to 4 hours. The metabolites are expected to be longer than the parent drug.

Copper is chelated by forming a stable complex with the four constituent nitrogens in a planar ring as copper displays enhanced ligand binding properties for nitrogen compared to oxygen. It binds Cu(II) very tightly, having a dissociation constant from Cu(II) of 10^−15 mol/L at pH 7.0 . TETA reacts in a stoichiometric ratio 1:1 with copper and is also able to complex with iron and zinc in vivo. TETA is considered a potential chemotherapeutic agent as it could be a telomerase inhibitor because it is a ligand for G-quadruplex, and stabilizes both intra- and intermolecular G-quadruplexes. It may mediate a selective inhibitory effect or cytotoxicity on tumor growth. Chelating excess copper may affect copper-induced angiogenesis. Other mechanisms of action of TETA for alternative therapeutic implications include improved antioxidant defense against oxidative stress, pro-apoptosis, and reduced inflammation.

Vapors from hot liquid can irritate eyes and upper respiratory system. Liquid burns eyes and skin. May cause sensitization of skin. (USCG, 1999)|Corrosives

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. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. 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. Corrosive chemicals will destroy the membranes of the mouth, throat, and esophagus and, in addition, have a high risk of being aspirated into the victim's lungs during vomiting which increases the medical problems. 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. 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. Transport the victim IMMEDIATELY to a hospital. (NTP, 1992)

Fresh air, rest. Half-upright position. Refer immediately for medical attention.

First rinse with plenty of water for at least 15 minutes, then remove contaminated clothes and rinse again. Refer immediately for medical attention.

Rinse with plenty of water (remove contact lenses if easily possible). Refer immediately for medical attention.

EXPOSURE TO THE HOT VAPOR RESULTS IN RESPIRATORY TRACT IRRITATION AND ITCHING OF THE FACE WITH ERYTHEMA AND EDEMA.|...MARKED SENSITIZATION /NOTED/ IN 6-20 WORKMEN EMPLOYED IN ELECTRICAL EQUIPMENT...FACTORY. THIS SHOWED ITSELF AS SERIOUS SKIN LESIONS, VESICULAR PAPULAR ECZEMA, SOMETIMES WEEPING, LOCALIZED PARTICULARLY ON HANDS, FOREARMS, & GENITAL & INGUINAL REGIONS, TOGETHER WITH FACIAL EDEMA.

Syprine

The substance can be absorbed into the body by inhalation of its vapour, through the skin and by ingestion. Serious local effects by all routes of exposure.

Sore throat. Cough. Burning sensation. Laboured breathing. Shortness of breath.

Redness. Pain. Skin burns. Blisters.

Redness. Pain. Loss of vision. Severe deep burns.

GRADES: TECHNICAL; ANHYDROUS.

Adhesive manufacturing|1,2-Ethanediamine, N1,N2-bis(2-aminoethyl)-: ACTIVE

Human drugs -> Cuprior -> EMA Drug Category|Other alimentary tract and metabolism products -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Health Hazards -> Corrosives