クロロトリアニセン

CRYSTALS FROM METHANOL

SMALL WHITE CRYSTALS, OR AS CRYSTALLINE POWDER; EXHIBITS POLYMORPHISM

less than 0.1 mg/mL at 66 °F (NTP, 1992)

PRACTICALLY INSOL IN WATER; SOL IN ALCOHOL 0.28 G/100 ML; IN ETHER 3.6 G/100 ML; SOL IN GLACIAL ACETIC ACID, CARBON TETRACHLORIDE, VEGETABLE OILS

1 G SOL IN 360 ML OF METHANOL, 7 ML ACETONE, 2.5 ML BENZENE, IN ABOUT 1.5 ML CHLOROFORM; PRACTICALLY INSOL IN 2,2,4-TRIMETHYLPENTANE

1.99e-04 g/L

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

237 to 241 °F (NTP, 1992)

113-114

114-116 °C

115 °C

Small white crystals or white powder. Softens at 226 °F. Odorless. (NTP, 1992)

Solid

SOFTENS AT 108 °C

ONE FORM MELTING @ ABOUT 116 °C & OTHER @ ABOUT 118 °C

CHLOROTRIANISENE may react vigorously with strong oxidizing agents. Can react exothermically with reducing agents (such as alkali metals and hydrides) to release gaseous hydrogen. May react exothermically with both acids and bases. Various catalysts (such as acids) or initiators can cause very exothermic addition polymerization reactions.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

RELATED, NONESTROGENIC COMPD ETHAMOXYTRIPHETOL WAS FOUND TO BE STRIKINGLY ANTIESTROGENIC. IT INHIBITED...ESTROGEN GIVEN IN FORM OF NATURAL COMPD...CHLOROTRIANISENE.

ESTRADIOL NORMALLY CAUSES PRONOUNCED ENLARGEMENT OF PITUITARY, BUT WHEN CHLOROTRIANISENE WAS GIVEN CONCURRENTLY EFFECT WAS GREATLY REDUCED.

NEUROOPHTHALMIC LESIONS DURING ESTROGEN TREATMENT HAVE BEEN DESCRIBED. HYPERCALCEMIA MAY OCCUR, ESP IN MEN TAKING LARGE DOSES FOR PROSTATIC CARCINOMA. ALLERGIC REACTIONS INCL RASHES, ERYTHEMA MULTIFORME, ERYTHEMA NODOSUM, & CHOLESTATIC JAUNDICE. /ESTROGENS/

LEVEL OF ANTITHROMBIN III REMAINED AT DEPRESSED LEVEL IN WOMEN GIVEN 72 MG CHLOROTRIANISENE (TACE) ORALLY EVERY 12 HR FOR 4 DOSES. DEPRESSED LEVELS OF ANTITHROMBIN III MAY BE RISK FACTOR IN DEVELOPING THROMBOEMBOLISM.

SYNTHETIC NON-STEROIDAL ESTROGENS INCL...CHLOROTRIANISENE... ALTHOUGH LITTLE INFORMATION APPEARS TO BE AVAIL, THESE COMPD MUST HAVE VERY LOW SINGLE DOSE TOXICITY.

Chlorotrianisene (CT) was evaluated for mutagenicity in the Salmonella/microsome preincubation assay using a standard protocol approved by the National Toxicology Program. CT was tested at doses of 0, 67, 100, 167, 333, 667, 1000, 1667, 3333, and 10,000 ug/plate in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) in the presence and absence of Aroclor-induced rat or hamster liver S9. CT was negative in these tests and the highest ineffective dose level tested without formation of a precipitate in any Salmonella tester strain was 333 ug/plate.

G - Genito urinary system and sex hormones

QG - Genito urinary system and sex hormones

Chlorotrianisene is a nonsteroidal synthetic estrogen. After menopause, when the body no longer produces estrogen, chlorotrianisene is used as a simple replacement of estrogen. The estrogen-stimulated endometrium may bleed within 48-72 hours after discontinuance of estrogen therapy. Paradoxically, prolonged estrogen therapy may cause shrinkage of the endometrium and an increase in size of the myometrium. Estrogens have a weak anabolic effect and may cause sodium retention with associated fluid retention and edema. Estrogens may also decrease elevated blood cholesterol and phospholipid concentrations. Estrogens affect bone by increasing calcium deposition and accelerating epiphyseal closure, following initial growth stimulation. During the preovulatory or nonovulatory phase of the menstrual cycle, estrogen is the principal determinant in the onset of menstruation. A decline of estrogenic activity at the end of the menstrual cycle also may induce menstruation; however, the cessation of progesterone secretion is the most important factor during the mature ovulatory phase of the menstrual cycle. The benefit derived from estrogen therapy in the prevention of postpartum breast engorgement must be carefully weighed against the potential increased risk of puerperal thromboembolism associated with the use of large doses of estrogens.

Chlorotrianisene binds to the estrogen receptor on various estrogen receptor bearing cells. Target cells include cells in the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.

Metabolized principally in the liver, although the kidneys, gonads, and muscle tissues may be involved to some extent. The metabolic fate of the synthetic estrogens has not been fully elucidated.

RATE OF O-DEMETHYLATION WAS MAXIMAL AT 0.4 MMOLAR NADPH. ALTHOUGH NADH DID NOT CATALYZE REACTION ALONE, IT HAD SYNERGISTIC EFFECT IN PRESENCE OF EQUIMOLAR AMT OF NADPH. EXTRACTS FROM INCUBATION MIXT CONTAINED 1 MAJOR (MONO-O-DEMETHYLATED) & A MINOR (BIS-O-DEMETHYLATED) METAB.

Non-steroidal compounds with estrogenic activity.

Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)

Absorption following oral administration is rapid.

...LONG-ACTING...BECAUSE OF SEQUESTRATION IN ADIPOSE TISSUE &, THEREFORE, IS NOT WIDELY USED.

...SUGGESTS THAT DRUG IS CONVERTED IN LIVER TO MORE ACTIVE FORM. ... IT IS STORED IN FAT, FROM WHICH IT IS SLOWLY RELEASED TO GIVE SUSTAINED ACTION.

ESTROGENIC ACTIVITY HAS BEEN FOUND IN ADIPOSE TISSUE UP TO MONTH AFTER CESSATION OF THERAPY.