Triethylenephosphoramide

106 °F (USCG, 1999)

41 °C

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.

Restricted substance: Tris(aziridinyl)phosphinoxide

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

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

· Combustible material: may burn but does not ignite readily.

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)

· Highly toxic, may be fatal if inhaled, ingested or absorbed through skin.

No longer used or produced commercially in the US; [HSDB] Known human carcinogen; [Merck Index] Prolonged contact can burn skin and eyes; Repeated exposure may lead to sensitization; Toxic by ingestion, inhalation, or skin absorption; [CAMEO] See Thiotepa.

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/

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)

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.