Triethylenephosphoramide

173.156

173.15

208-892-5

GL19M2KE52

221657|9717

2501

DTXSID4052716

COLORLESS CRYSTALS

2933990090

26.1

-3.16 (calculated)

Tris(1-aziridinyl) phosphine oxide appears as a colorless crystalline solid. Shipped as an aqueous solution. Toxic by skin absorption, ingestion or inhalation. Produces toxic oxides of nitrogen during combustion. Used as a pesticide.

0.99

41 °C

90-91 °C @ Press: 23 Torr

163°C o.c.

1.634

Solubility in water: miscible

Vapour pressure, Pa at 20°C: 1.3

Relative vapour density (air = 1): 6.5

LD50 orally in male rats: 37 mg/kg (Gaines)

vol% in air: 0.1 15

No rapid reaction with air. No rapid reaction with water.

Esters, Sulfate Esters, Phosphate Esters, Thiophosphate Esters, and Borate Esters

Polymerizable

TRIS-(1-AZIRIDINYL) PHOSPHINE OXIDE may react with aqueous solutions of acids or strong bases. Undergoes slow decomposition in water, not considered hazardous. Polymerizes violently at about 255°F. Acid fumes also cause polymerization at ordinary temperatures (USCG, 1999). May produce highly toxic and flammable phosphine gas in the presence of strong reducing agents such as hydrides. Partial oxidation by oxidizing agents may result in the release of toxic phosphorus oxides.

III

6.1(b)

UN 2811

(1/2)-26-36/37/39-45-61

SZ1750000

C, N

Provision to contain effluent from fire extinguishing. Separated from strong acids, strong oxidants, chlorinated hydrocarbons and food and feedstuffs. Dry. Store in an area without drain or sewer access.

Stable.

A REVIEW WITH 74 REFERENCES ON THE COMPARATIVE MUTAGENICITY OF TEPA, THIOTEPA, & METEPA.[BOCHOV NP; COMPARATIVE MUTAGENICITY OF TEPA, THIOTEPA, AND METEPA; ENVIRON SCI RES 24 (COMP CHEM MUTAGEN): 917-42 (1981)]

Special Hazards of Combustion Products: Phosphoric acid mist may form in fire. Toxic oxides of nitrogen may form. (USCG, 1999)

Excerpt from ERG Guide 152 [Substances - Toxic (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 152 [Substances - Toxic (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 152 [Substances - Toxic (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. Cover with plastic sheet to prevent spreading. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS. (ERG, 2016)

Protective clothing and gloves to prevent contact with skin; goggles. (USCG, 1999)

/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Health: Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin. 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. /Tris-(1-aziridinyl)phosphine oxide, solution/|/GUIDE 152: SUBSTANCES - TOXIC (COMBUSTIBLE)/ Fire or Explosion: Combustible material: may burn but does not ignite readily. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form. /Tris-(1-aziridinyl)phosphine oxide, solution/|/GUIDE 152: SUBSTANCES - TOXIC (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. /Tris-(1-aziridinyl)phosphine oxide, solution/|/GUIDE 152: SUBSTANCES - TOXIC (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. /Tris-(1-aziridinyl)phosphine oxide, solution/|For more DOT Emergency Guidelines (Complete) data for TEPA (8 total), please visit the HSDB record page.

Alkylating Agents; Antineoplastic Agents, Alkylating; Chemosterilants|SINCE THE FORMATION OF THE ETHYLENIMONIUM ION CONSTITUTES THE INITIAL REACTION OF THE NITROGEN MUSTARDS, SCREENING PROGRAMS HAVE BEEN DEVISED TO DISCOVER USEFUL ETHYLENIMINE DERIVATIVES. THESE STUDIES HAVE YIELDED SEVERAL ACTIVE COMPOUNDS, INCLUDING...TRIETHYLENEPHOSPHORAMIDE (TEPA)... WHILE TEM, TEPA, & THIOTEPA ARE CYTOTOXIC, THEY HAVE NO PARTICULAR CLINICAL ADVANTAGE OVER THE OTHER ALKYLATING AGENTS.|CHEMOTHERAPEUTIC ALKYLATING AGENT

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.)

AFTER IP ADMIN OF (32)P-TEPA TO MICE, RADIOACTIVITY WAS NOT LOCALIZED SELECTIVELY IN ANY OF TISSUES EXAMINED. DURING FIRST 24 HR AFTER TREATMENT SOME 60-75% OF DOSE WAS EXCRETED VIA URINE, COMPARED WITH ONLY 2-5% IN FECES. IN URINE, 80% OF RADIOACTIVITY WAS IDENTIFIED AS INORGANIC PHOSPHATE, REMAINDER AS AN UNIDENTIFIED METABOLITE WHICH COULD BE HYDROLYZED TO GIVE ORGANIC PHOSPHATE. IN RATS, 80% OF RADIOACTIVITY IN BLOOD WAS ASSOC WITH HEMOGLOBIN. DURING FIRST 24 HR 89-90% OF RADIOACTIVITY WAS EXCRETED IN URINE; HOWEVER, IN CONTRAST WITH MOUSE, 50-70% OF URINARY RADIOACTIVITY WAS PRESENT AS UNCHANGED TEPA. PATTERN OF METAB IN DOGS IS ESSENTIALLY SIMILAR TO THAT...FOR RATS. RECOVERY OF UNCHANGED TEPA IN URINE WAS ABOUT 25-30% OF DOSE OVER SAME PERIOD. TISSUE DISTRIBUTION STUDIES SHOWED...RETENTION WAS UNIFORMLY LOW, WITH EXCEPTION OF BONE MARROW IN WHICH SELECTIVE UPTAKE RESULTED IN CONCN 6-10 TIMES THAT...IN OTHER TISSUES.|THE SPERM-RICH FRACTION OF BOAR SEMEN WAS TREATED IN VITRO FOR 10 MIN WITH AN EQUAL VOL OF 1% SOLN OF (14)C-LABELED TEPA. ON AVERAGE, 0.8% WAS TAKEN UP IN THE SPERMATOZOA; 69% WAS ASSOCIATED WITH THE HEADS & 31% WITH THE TAILS & ACROSOMES.

THE MOST IMPORTANT PHARMACOLOGICAL ACTIONS OF THE ALKYLATING AGENTS ARE THOSE THAT DISTURB THE FUNDAMENTAL MECHANISMS CONCERNED WITH CELL GROWTH, MITOTIC ACTIVITY, DIFFERENTIATION, & FUNCTION. THE CAPACITY OF THESE DRUGS TO INTERFERE WITH NORMAL MITOSIS & CELL DIVISION IN ALL RAPIDLY PROLIFERATING TISSUES PROVIDES THE BASIS FOR THEIR THERAPEUTIC APPLICATIONS & FOR MANY OF THEIR TOXIC PROPERTIES. /ALKYLATING AGENTS/

Inhalation (unlikely unless a heavy mist is formed) causes symptoms similar to those observed after ingestion. Contact with liquid or powder causes irritation of eyes and (on prolonged contact) irritation and burns of skin. Burns are slow to develop and slow to heal. May sensitize on repeated contact. Ingestion causes depression, anorexia, and diarrhea, appearing 2-3 days before death, followed by terminal dyspnea, incoordination, epistaxis, salivation, prostration and cyanosis. (USCG, 1999)

INHALATION: remove victim to fresh air. EYES: flush with water at once for at least 15 min.; get medical attention. SKIN: flush with water at once, followed by vinegar and dilute hydrogen peroxide. INGESTION: only symptomatic and supportive measures are available. (USCG, 1999)

HIGH FREQUENCY OF CHROMOSOME ABERRATIONS WAS OBSERVED IN VITRO AFTER TREATMENT OF HUMAN LEUCOCYTE CULTURES WITH TEPA.|THE FREQUENCY OF SISTER CHROMATID EXCHANGES (SCE) & CHROMOSOME ABERRATIONS & THE DYNAMICS OF CELL DIVISION IN PERIPHERAL BLOOD LYMPHOCYTES OF 4 PATIENTS WITH FANCONI'S ANEMIA WERE STUDIED AFTER IN VITRO EXPOSURE TO ALKYLATING AGENTS TEPA & MITOMYCIN. SCE FREQUENCY WAS SIGNIFICANTLY INCREASED EVEN AFTER VERY LOW DOSES OF MUTAGENS, WHILE CHROMOSOME ABERRATIONS WERE SIGNIFICANTLY INCREASED ONLY AFTER HIGH DOSES (0.160 MUG/ML MITOMYCIN & 10-5 MOLES TEPA).

TEPA

...FLAME-RETARDANT TREATMENT OF MILITARY COTTON...WAS TERMINATED WHEN SOLE US COMMERCIAL MANUFACTURER DISCONTINUED PRODUCTION FOR ECONOMIC REASONS.|CLINICAL TRIALS OF TEPA AS ANTINEOPLASTIC AGENT WERE REPORTED IN US IN 1953. ALTHOUGH IT WAS TESTED IN ANIMALS & HUMANS, IT WAS NEVER EXTENSIVELY USED IN CANCER THERAPY DUE TO DISCOVERY OF EQUALLY EFFECTIVE BUT LESS TOXIC SULFUR ANALOGUE, TRIS-(1-AZIRIDINYL)PHOSPHINE SULFIDE. ALTHOUGH TEPA WAS SHOWN TO BE EFFECTIVE AS CHEMOSTERILANT FOR VARIETY OF INSECTS /1964/, PROBLEMS ASSOC WITH ITS APPLICATION TO INSECTS, ITS TOXICITY & ENVIRONMENTAL EFFECTS HAVE PREVENTED ITS USE IN THIS WAY ON COMMERCIAL BASIS. TEPA HAS BEEN USED AS ACARICIDE...

SEPARATION OF TEPA FROM PREPN OF PULVERIZED INSECTS PRIOR TO ITS DETERMINATION BY COLORIMETRIC PROCEDURES HAS BEEN ACHIEVED BY USE OF COLUMNS CONTAINING ANHYDROUS SODIUM SULFATE & SILICA GEL (COLLIER CW, TARDIF R; ANAL OF MALE GYPSY MOTHS FOR MICROGRAM QUANTITIES OF TEPA; J ECON ENTOMOL 60: 28 (1967)).|SPECTROPHOTOFLUORIMETRIC METHOD...FOR DETERMINATIONS IN 0.05-0.2 UG/ML BODY FLUID, HAS BEEN USED TO DETERMINE TEPA IN PRESENCE OF TRIS(1-AZIRIDINYL)PHOSPHINE SULFIDE IN EXTRACTS OF BIOL TISSUES & FLUIDS...(MELLETT LB, WOODS LA; COMPARATIVE PHYSIOLOGICAL DISPOSITION OF THIOTEPA AND TEPA IN DOG; CANCER RES 20: 524 (1960)).|...GAS CHROMATOGRAPHIC PROCEDURES HAVE PROVIDED METHODS OF ANALYSIS SENSITIVE TO 0.1 NG. RETENTION TIMES FOR TEPA HAVE BEEN REPORTED & PROCEDURE DIRECTLY APPLICABLE TO METHANOLIC EXTRACTS OF INSECT TISSUES...DESCRIBED (SEAWRIGHT JA ET AL; TEPA & THIOTEPA: UPTAKE, PERSISTENCE & STABILITY INDUCED IN PUPAE & ADULTS OF CULEX PIPIENS QUINQUEFASCIATUS; J ECON ENTOMOL 64: 452 (1971)).

CHEMOSTERILANTS