Chlorotrianisene

380.86

380.86

209-318-6

6V5034L121

10108

DTXSID1021299

C65320

CRYSTALS FROM METHANOL|SMALL WHITE CRYSTALS, OR AS CRYSTALLINE POWDER; EXHIBITS POLYMORPHISM

G - Genito urinary system and sex hormones

27.7

6.4

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

1.168g/cm3

114-116 °C

514.2ºC at 760mmHg

164.1ºC

1.591

1.99e-04 g/L

-70°C

ODORLESS

SOFTENS AT 108 °C|ONE FORM MELTING @ ABOUT 116 °C & OTHER @ ABOUT 118 °C

Sensitive to prolonged exposure to air and light. Insoluble in water.

Ethers

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.

3

KV0600000

STABLE IN AIR

Flash point data for this chemical are not available. It is probably combustible. (NTP, 1992)

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

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. STORAGE PRECAUTIONS: You should protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)

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)

Acute overdosage of large doses of oral contraceptives in chidren reportedly produces almost no toxicity except nausea and vomiting. Acute overdosage of estrogens may cause nausea, and withdrawal bleeding may occur in females.

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.

50-80%

Used to treat symptoms of menopause, deficiencies in ovary function (including underdevelopment of female sexual characteristics and some types of infertility), and in rare cases, prostate cancer. Chlorotrianisene may also be used to prevent breast engorgement following childbirth.

Antineoplastic Agents, Hormonal; Estrogens, Non-Steroidal|...REPORTED RELIEF OF DYSMENORRHEA BY INHIBITING OVULATION WITH ESTROGEN. ... USE OF ESTROGENS IN TREATMENT OF ENDOMETRIOSIS... FAILURE OF OVARIAN DEVELOPMENT...IS TREATED WITH ESTROGEN... COMMON FORM OF ACNE IS FEATURE OF PUBERTY... TREATMENT WITH ESTROGEN IS EFFECTIVE... /ESTROGENS/|SENILE OR ATROPHIC VAGINITIS, OFTEN ASSOC WITH CHRONIC INFECTION OF ATROPHIC STRUCTURES, RESPONDS WELL TO ESTROGEN. KRAUROSIS VULVAE, DISTRESSINGLY ITCHY CONDITION DUE IN PART TO DEFICIENCY IN ESTROGEN...IS FAVORABLY INFLUENCED BY ESTROGEN SUPPLEMENTED BY LOCAL TREATMENT... /ESTROGENS/|...UNIQUE IN THAT ITS POTENCY IS GREATER BY ORAL THAN BY ANY OTHER ROUTE...|For more Therapeutic Uses (Complete) data for CHLOROTRIANISENE (7 total), please visit the HSDB record page.

...LONG DURATION OF ACTION MAKES THIS DRUG UNSUITABLE FOR TREATMENT OF MENSTRUAL DISORDERS & OTHER CONDITIONS IN WHICH CYCLIC THERAPY IS DESIRED.|...PREGNANT PT SHOULD NOT BE GIVEN ESTROGENS, PARTICULARLY DURING 1ST TRIMESTER-TIME WHEN FETAL REPRODUCTIVE TRACT IS DEVELOPING & MAY BE INFLUENCED BY EXOGENOUS ESTROGENS. /ESTROGENS/|...IS RELATED TO TRIPARANOL & TO CLOMIPHENE, BOTH OF WHICH CAN PRODUCE CATARACTS IN CERTAIN CIRCUMSTANCES. THIS SEEMS TO BE REASON FOR WATCHING FOR CATARACTS WHEN USING CHLOROTRIANISENE, BUT SO FAR THIS DRUG HAS NOT BEEN DEMONSTRATED TO PRODUCE THEM.

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.

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) (See all compounds classified as Antineoplastic Agents, Hormonal.)|Non-steroidal compounds with estrogenic activity. (See all compounds classified as Estrogens, Non-Steroidal.)

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.

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.

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.

SYMPTOMS: When ingested, this compound can cause headache, nausea, vomiting, gynecomastia and sometimes vaginal bleeding. ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits very toxic fumes. (NTP, 1992)

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. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

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

CHLOROTRIANISENE, NF (TACE), IS LONG-ACTING ORAL PREPN... IT IS AVAIL IN 12-, 25-, & 72-MG CAPSULES & HAS ABOUT 1/8 ACTIVITY OF DIETHYLSTILBESTROL.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients