Thiotepa Chemische Eigenschaften,Einsatz,Produktion Methoden
R-Sätze Betriebsanweisung:
R45:Kann Krebs erzeugen.
R46:Kann vererbbare Schäden verursachen.
R28:Sehr giftig beim Verschlucken.
S-Sätze Betriebsanweisung:
S53:Exposition vermeiden - vor Gebrauch besondere Anweisungen einholen.
S22:Staub nicht einatmen.
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
S36/37:Bei der Arbeit geeignete Schutzhandschuhe und Schutzkleidung tragen.
S28:Bei Berührung mit der Haut sofort abwaschen mit viel . . . (vom Hersteller anzugeben).
Beschreibung
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).
Chemische Eigenschaften
white crystals or powder
Verwenden
Tri(1-aziridinyl)phosphine sulfide is useful for the treatment of cancers, especially cancers resistant to chemotherapy. Antineoplastic. Thio-TEPA (N,N?N?-triethylenethiophosphoramide) is used as a cancer chemotherapeutic, alkylating agent. It is used to treat various kinds of cancer such as breast, ovarian and bladder cancer. It is also used as conditioning treatment prior to hematopoietic progenitor cell transplantation (HPCT)
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.
Allgemeine Beschreibung
Odorless white crystalline solid.
Air & Water Reaktionen
Water soluble.
Reaktivität anzeigen
Triethylenethiophosphoramide polymerizes readily upon exposure to heat or moisture, especially at acidic pH.
Hazard
Confirmed carcinogen.
Brandgefahr
Flash point data for Triethylenethiophosphoramide are not available. Triethylenethiophosphoramide is probably combustible.
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.
Nebenwirkungen
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.
Sicherheitsprofil
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.
mögliche Exposition
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.
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.
Versand/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.
Inkompatibilitäten
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.
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.
Thiotepa Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
