| Identification | Back Directory | [Name]
Triethylenethiophosphoramide | [CAS]
52-24-4 | [Synonyms]
stepa
tespa
sk6882
tifosyl
nsc6396
THIOTEF
TIO-TEF
THIO-TEP
wr-45312
TIOFOSYL
TIOFOZIL
girostan
nsc-6396
oncotepa
tespamin
tespamine
Thiofosyl
cbc806495
ledertepa
THIOFOZIL
THIO-TEPA
nci-c01649
thio-tepas
AI 3-24916
oncotiotepa
TIOFOSFAMID
thiotepa，TSPA
oncothio-tepa
thiophosphamide
thiophosphoramide
Thiotepa (500 mg)
Triethylenethiophosp
SALOR-INT L169250-1EA
ThiophosphraMide,Thio-TEPA
phosphorictri(ethyleneamide)
thiotriethylenephosphoramide
TRIETHYLENETHIOPHOSPHORAMIDE
triaziridinylphosphinesulfide
tris(ethylenimino)thiophosphate
triethylenethiophosphorotriamide
TRIS(AZIRIDINYL)PHOSPHINESULPHIDE
TRIS(AZIRIDINYL)PHOSPHINE SULFIDE
n,n’,n"-triethylenethiophosphamide
Triethylenethiophosphoramide, 98+%
tris(1-aziridinyl)-phosphinesulfid
Tri(1-aziridinyl)phosphine sulfide
Phosphorothioic Acid Triethylenetr
Tri(aziridin-1-yl)phosphine sulfide
tri(ethyleneimino)thiophosphoramide
n,n’,n’’-triethylenethiophosphamide
tris(1-aziridinyl)phosphinesulphide
TRIS(L-AZIRIDINYL)PHOSPHINESULPHIDE
TRIS(1-AZIRIDINYL)PHOSPHINE SULFIDE
n,n’,n"-triethylene-thiophosphoramid
1,1',1''-Phosphorothioyltriaziridine
N,N',N''-TRIETHYLENETHIOPHOSPHORAMIDE
phosphorothioicacidtriethylenetriamide
Thiotepa(TriethylenethiophosphoraMide)
n,n’,n’’-triethylenethiophosphortriamide
1,1,1"-phosphinothioylidynetris-aziridin
1,1’,1’’-phosphinothioylidynetris-aziridin
1,1’,1’’-phosphinothioylidynetrisaziridine
n,n’,n"-triethylene-phosphorothioictriamid
n,n’,n’’-triethylene-phosphorothioictriamid
n,n’,n’’-triethylenephosphorothioictriamide
n,n’,n’’-tri-1,2-ethanediyl-thiophosphoramid
n,n’,n’’-tri-1,2-ethanediylthiophosphoramide
Aziridine,1,1',1''-phosphinothioylidynetris-
TRIS(1-AZIRIDINYL)PHOSPHINESULPHIDE(THIOTEPA)
n,n’,n’’-tri-1,2-ethanediyl-phosphorothioictriamid
n,n’,n’’-tri-1,2-ethanediylphosphorothioictriamide
N,Nμ,N-Triethylenethiophosphoramide, Thio-Tep, Thiofozil, Thiotef, Tio-tef, Tiofosfamid, Tiofosyl, Tiofozil, Tris(aziridinyl)phosphine sulfide | [EINECS(EC#)]
200-135-7 | [Molecular Formula]
C6H12N3PS | [MDL Number]
MFCD00145452 | [MOL File]
52-24-4.mol | [Molecular Weight]
189.22 |
| Chemical Properties | Back Directory | [Appearance]
Thiotepa is a crystalline substance. | [Melting point ]
54-57 °C
| [Boiling point ]
270.2±23.0 °C(Predicted) | [density ]
1.50±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C
| [solubility ]
Soluble in benzene, acetone and methanol. | [form ]
solid
| [pka]
2.74±0.20(Predicted) | [color ]
white | [Stability:]
Stable. Incompatible with strong oxidizing agents. | [Water Solubility ]
19 g/100 mL (25 ºC) | [InChIKey]
FOCVUCIESVLUNU-UHFFFAOYSA-N | [CAS DataBase Reference]
52-24-4 | [IARC]
1 (Vol. Sup 7, 50, 100A) 2012 | [NIST Chemistry Reference]
Thiotepa(52-24-4) | [EPA Substance Registry System]
Aziridine, 1,1',1''-phosphinothioylidynetris- (52-24-4) |
| Hazard Information | Back Directory | [Chemical Properties]
white crystals or powder | [Uses]
antiseborrheic, antipruritic | [Uses]
suzuki reaction | [Uses]
This substance is listed as a known human carcinogen. It is useful for the treatment of cancers, especially cancers resistant to chemotherapy. Antineoplastic. | [Uses]
Insect sterilant. | [General Description]
Odorless white crystalline solid. | [Air & Water Reactions]
Water soluble. | [Reactivity Profile]
Triethylenethiophosphoramide polymerizes readily upon exposure to heat or moisture, especially at acidic pH. | [Fire Hazard]
Flash point data for Triethylenethiophosphoramide are not available. Triethylenethiophosphoramide is probably combustible. | [Potential Exposure]
Used in the treatment of cancers resistant to chemotherapy. Antineoplastic: thiotepa has been prescribed for a wide variety of neoplastic diseases: adenocarcinomas of the breast and the ovary; superficial carcinoma of the urinary bladder; controlling intracavitary or localized neoplastic disease; lymphomas, such aslymphosarcomas and Hodgkin’s disease; as well as bronchogenic carcinoma. | [First aid]
If this chemical gets into the eyes, remove any contact lenses at once and irrigate immediately for at least 15 minutes, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts the skin, remove contaminated clothing and wash immediately with soap and water. Seek medical attention immediately. If this chemical has been inhaled, remove from exposure, begin rescue breathing (using universal precautions,including resuscitation mask) if breathing has stopped and CPR if heart action has stopped. Transfer promptly to a medical facility. When this chemical has been swallowed, get medical attention. Give large quantities of water and induce vomiting. Do not make an unconscious person vomit. | [Shipping]
UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required. UN3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials. | [Incompatibilities]
Tris(aziridinyl)phosphine sulfide polymerizes readily upon exposure to heat or moisture, especially at acidic pH. Incompatible with strong oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides. | [Description]
Thiotepa, a tertiary aziridine, is less reactive than quaternary aziridinium compounds and is classified as a weak alkylator. It is possible for the nitrogen atoms to be protonate before reacting with DNA (a positively charged aziridine is more reactive than the un-ionized aziridine), but the electron-withdrawing effect of the sulfur atom decreases the pKa to approximately six, which keeps the percentage ionized at pH 7.4 relatively low. Thiotepa undergoes oxidative desulfuration, forming an active cytotoxic metabolite known as TEPA (triethylenephosphoramide). | [Waste Disposal]
It is inappropriate and possibly dangerous to the environment to dispose of expired or waste pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator. | [Originator]
Thio-Tepa,Lederle,US,1959 | [Definition]
ChEBI:Thiotepa is a member of aziridines. | [Indications]
Although thiotepa is chemically less reactive than the nitrogen
mustards, it is thought to act by similar mechanisms.
Its oral absorption is erratic. After intravenous injection,
the plasma half-life is less than 2 hours. Urinary
excretion accounts for 60 to 80% of eliminated drug.
Thiotepa has antitumor activity against ovarian and
breast cancers and lymphomas. However, it has been
largely supplanted by cyclophosphamide and other nitrogen
mustards for treatment of these diseases. It is
used by direct instillation into the bladder for multifocal
local bladder carcinoma.
Nausea and myelosuppression are the major toxicities
of thiotepa. It is not a local vesicant and has been
safely injected intramuscularly and even intrathecally. | [Manufacturing Process]
A solution of 30.3 parts of triethylamine and 12.9 parts of ethylenimine in 180
parts of dry benzene is treated with a solution of 16.9 parts of thiophosphoryl
chloride in 90 parts of dry benzene at 5°C to 10°C. Triethylamine
hydrochloride is filtered off. The benzene solvent is distilled from the filtrate
under reduced pressure and the resulting crude product is recrystallized from
petroleum ether. The N,N',N''-triethylenethiophosphoramide had a melting
point of 51.5°C. | [Therapeutic Function]
Antineoplastic | [Hazard]
Confirmed carcinogen. | [Biochem/physiol Actions]
The unstable nitrogen-carbon groups alkylate with DNA which causes irreversible DNA damage. They stop tumor growth by crosslinking guanine nucleobases in DNA double-helix strands, directly attacking DNA. The DNA strands are unable to uncoil and separate which halts cell division. | [Mechanism of action]
Thiotepa and the TEPA metabolite readily enter the CNS after systemic administration, leading to dizziness, blurred vision, and headaches. More critically, these agents also are severe myelosuppressants and can induce leukopenia, thrombocytopenia, and anemia. Patients treated with thiotepa are at high risk for infection and hemorrhage. | [Clinical Use]
This antineoplastic agent is most commonly employed in the treatment of ovarian and breast cancers, as well as papillary carcinoma of the bladder.
| [Side effects]
Patients have died from myelosuppression after intravesically administered thiotepa. The drug also causes damage to the hepatic and renal systems. Dose and/or administration frequency should be increased slowly, even if the initial response to the drug is sluggish, or unacceptable toxicity may result. | [Synthesis]
Thiotepa, tris(1-aziridinyl)phosphine sulfate (30.2.2.1), is made by reacting
ethylenimine with phosphorous sulfochloride .
| [Drug interactions]
Potentially hazardous interactions with other drugs
Antipsychotics: avoid concomitant use with clozapine.
Avoid concomitant use with other myelosuppressive agents. Administration | [Carcinogenicity]
Thiotepa is known to be a human carcinogen based on sufficient evidence from studies in humans. Thiotepa was first listed in the Second Annual Report on Carcinogens in 1981 as reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals and insufficient evidenceof carcinogenicity from studies in humans. Thiotepa was reclassified as known to be a human carcinogen in the Eighth Report on Carcinogens in 1998. | [Metabolism]
Thiotepa is extensively metabolised to triethylenephosphoramide (TEPA), the primary metabolite, and some of the other metabolites have cytotoxic activity and are eliminated more slowly than the parent compound. It is excreted in the urine: less than 2
% of a dose is reported to be present as unchanged drug or its primary metabolite. | [storage]
4°C, protect from light | [Toxicity evaluation]
One of the principal bond disruptions is initiated by alkylation
of guanine at the N-7 position, which severs the linkage
between the purine base and the sugar and liberates alkylated
guanines. This causes DNA cross-linking and prevents the
replication of rapidly dividing cells. |
| Safety Data | Back Directory | [Hazard Codes ]
T+ | [Risk Statements ]
45-46-28 | [Safety Statements ]
53-22-26-36/37/39-45-36/37-28 | [RIDADR ]
UN 2811 6.1/PG 2
| [WGK Germany ]
3
| [RTECS ]
SZ2975000
| [HazardClass ]
6.1(a) | [PackingGroup ]
II | [HS Code ]
2933999552 | [Safety Profile]
Confirmed human
carcinogen producing leukemia. Poison by
ingestion, intraperitoneal, intravenous, and
subcutaneous routes. Experimental
teratogenic data. Human systemic effects by
parenteral route: paresthesia, bone marrow
changes, and leukemia. Experimental
reproductive effects. Human mutation data
reported. When heated to decomposition it
emits very toxic fumes of POx, SOx, and
NOx. | [Hazardous Substances Data]
52-24-4(Hazardous Substances Data) | [Toxicity]
LD50 i.v. in rats: 15 mg/kg (Scherf) |
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