化合物详情

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 12-O-tetradecanoylphorbol-13-acetate, which has an estimated vapor pressure of 1.8X10-17 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase 12-O-tetradecanoylphorbol-13-acetate may be removed from the air by wet and dry deposition(SRC). 12-O-Tetradecanoylphorbol-13-acetate absorbs at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 12-O-tetradecanoylphorbol-13-acetate can be estimated to 1.1X10+5(SRC). According to a classification scheme(2), this estimated Koc value suggests that 12-O-tetradecanoylphorbol-13-acetate is expected to be immobile in soil.

An estimated BCF of 2300 was calculated in fish for 12-O-tetradecanoylphorbol-13-acetate(SRC), using an estimated log Kow of 7.36(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC).

The Henry's Law constant for 12-O-tetradecanoylphorbol-13-acetate is estimated as 4.7X10-12 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 12-O-tetradecanoylphorbol-13-acetate is expected to be essentially nonvolatile from water surfaces(2). 12-O-Tetradecanoylphorbol-13-acetate's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). 12-O-Tetradecanoylphorbol-13-acetate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-17 mm Hg(SRC), determined from a fragment constant method(1).

The rate constant for the vapor-phase reaction of 12-O-tetradecanoylphorbol-13-acetate with photochemically-produced hydroxyl radicals has been estimated as 2.1X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.8 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). A base-catalyzed second-order hydrolysis rate constant of 0.042 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 5.3 years and 192 days at pH values of 7 and 8, respectively(1). 12-O-Tetradecanoylphorbol-13-acetate absorbs at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Protection from light is recommended for...

Phorbol esters have been identified in Sapium indicum, S. japonicum, Euphorbia frankiana, E. cocrulescence, E. ticulli, Croton spareiflorus, C. tiglium, C. ciliatoglandulifer, Jatropha curcas, Excoecaria agallocha and Homalanthus nutans. These esters are toxic(1). /Phorbol esters/

... croton oil.../derived/ from seeds of Croton tiglium L ... active constituents ... are diesters of a tetracyclic diterpene, phorbol. Fourteen diesters have been isolated from croton oil ... /of which/ most active biologically is 12-O-tetradecanoylphorbol-13-acetate ...

12-O-Tetradecanoylphorbol-13-acetate's production and use as a tumor promoter and activator of protein kinase C in cancer research(1,2) may result in its release to the environment through various waste streams(SRC). It is also known as purging cotton and used in traditional medicine(3).

Occupational exposure to 12-O-tetradecanoylphorbol-13-acetate may occur through dermal contact with this compound at workplaces where 12-O-tetradecanoylphorbol-13-acetate is produced or used(SRC). 12-O-Tetradecanoylphorbol-13-acetate is currently undergoing FDA-approved (Dec 28, 2015) clinical-stage treatment of AML (Acute myelogenous leukemia); 12-O-tetradecanoylphorbol-13-acetate is also being study in the treatment of Hodgkins Lymphoma(1). The general public is not likely to be exposed to 12-O-tetradecanoylphorbol-13-acetate unless by direct medical treatment(SRC).

12-O-Tetradecanoylphorbol-13-acetate's production and use as a tumor promoter and activator of protein kinase C in cancer research as well as administration in traditional medicine may result in its release to the environment through various waste streams. It occurs as a constituent in croton oil, the seed oil of Croton tiglium L. (Euphorbiaceae). If released to air, an estimated vapor pressure of 1.8X10-17 mm Hg at 25 °C indicates 12-O-tetradecanoylphorbol-13-acetate will exist solely in the particulate phase in the atmosphere. Particulate-phase 12-O-tetradecanoylphorbol-13-acetate will be removed from the atmosphere by wet and dry deposition. 12-O-Tetradecanoylphorbol-13-acetate absorbs at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight. If rele...

Reproductive Toxin - A chemical that is toxic to the reproductive system, including defects in the progeny and injury to male or female reproductive function. Reproductive toxicity includes developmental effects. See Guidelines for Reproductive Toxicity Risk Assessment.

IDENTIFICATION AND USE: TPA is a colorless powder. It is used in cancer research to study mechanisms of tumor promotion, to screen for potential inhibiting agents, and as positive control for tumor promoting agents. It has been tested as experimental medication for the treatment of leukemias and lymphomas and other types of cancer. HUMAN EXPOSURE AND TOXICITY: TPA is a human platelet aggregating agent. TPA was used in clinical trials in humans suffering from recurrent malignancies, particularly hematological malignancies including severe forms of leukemia. The objective of this trial was the use of TPA as an agent to induce, at low doses,apoptosis and cell differentiation. The TPA application was based on current protocols for cytostatic agents, and involved 35 patients given a low dose...

LD50 Mouse iv 309 ug/kg

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam...