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MINUTE NEEDLES FROM DILUTE ALC

WHITE NEEDLES FROM ETHANOL

COLORLESS OR WHITE, OR PRACTICALLY WHITE NEEDLE-LIKE CRYSTALS OR AS A WHITE, CRYSTALLINE POWDER

FREELY SOL IN ALC, METHANOL, ETHER, ACETONE, PROPYLENE GLYCOL; SOL IN CHLOROFORM, AQ SOLN OF ALKALI HYDROXIDES; SOLUBLE IN VEGETABLE OILS AFTER WARMING, BUT CRYSTALLIZES OUT ON STANDING; PRACTICALLY INSOL IN WATER, DIL ACIDS .

SOL IN FIXED OILS.

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

233-234

227-228 °C

PRISMS FROM ALC; MP: 119-120 °C /DIENESTROL DIACETATE/

SUBLIMES @ 130 °C @ 1 MM HG; THE SUBLIMATE MP: 231-234 °C

MP: 179 °C; HAS NO ESTROGENIC ACTIVITY /DIENESTROL ISODIENESTROL/

158.78 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

153.2 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Danger

H350 (100%): May cause cancer [Danger Carcinogenicity]

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl dienestrol, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act.

Gray LE Jr; Delayed Reproductive Effects Following Exposure to Toxic Chemicals During Critical Developmental Periods. NTIS Technical Report NTIS/PB90-112830 (1989). The studies presented in this review indicate that perinatal exposure of the fetal or neonatal rodent to a toxicant can adversely affect reproductive development, reduce fertility and accelerate reproductive senescence. In rodents and humans exposure to diethylstilbestrol, estrogens, androgens and progestins during critical developmental periods produce morphological and pathological alterations of the reproductive tract of males and females. Diethylstilbestrol treatment causes cancer, infertility and serious morphological abnormalities of the reproductive tract in all species examined.

Commercially available dienestrol vaginal cream should be stored at a temperature less than 40 °C, preferably between 15-30 °C; freezing should be avoided.

Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a collapsible tube or tight container. Protect from freezing. /Dienestrol cream USP/

Concurrent use with estrogens may alter the metabolism and protein binding of glucocorticoids, leading to decreased clearance, increased elimination half-life, and increased therapeutic and toxic effects of the glucocorticoids.

Estrogens may cause amenorrhea, interfering with effects of bromocriptine. /Estrogen/

Calcium supplements: concurrent use with estrogens may increase calcium absorption. /Estrogen/

Concurrent use with estrogens may potentiate the anti-inflammatory effects of endogenous cortisol induced by corticotropin. /Estrogen/

For more Interactions (Complete) data for DIENESTROL (9 total), please visit the HSDB record page.

The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition): ... Hepatic function determinations (recommended at regular intervals, especially during therapy in patients who have or are suspected of having hepatic disease); Lipid profile determinations, serum (recommended annually in women who are receiving estrogen replacement therapy, especially if taking a progestin); Mammogram (every 12 mo, or as determined by physician) Papanicolaou (Pap) test and Physical examinations (every 6 to 12 mo or more frequently when so determined by physician, with special attention being given to abdomen, breast, and pelvic organs)

BREAST ENLARGEMENT & NODULARITY OCCURRED IN BOTH MALE & FEMALE CHILDREN AFTER CONSUMPTION OF VITAMIN CAPSULES CONTAMINATED WITH ESTROGENS. /ESTROGENS/

ONE CASE OF ADENOCARCINOMA OF VAGINA HAS BEEN REPORTED IN YOUNG GIRL, 17 YR OLD, WHOSE MOTHER HAD TAKEN 5 MG/DAY DIENESTROL ORALLY & 2 IM DOSES OF ESTRONE DURING 3RD MONTH OF PREGNANCY ... .

MALAISE, IRRITABILITY, & DEPRESSION ... OCCUR WITH SMALL DOSES & ... WITH LARGE DOSES. EFFECT ON LIBIDO IS ERRATIC, BEING INCR IN SOME & DECR IN OTHERS. ... CHANGES IN CONCN OF SOME OF CLOTTING FACTORS IN BLOOD ... INCR INCIDENCE OF THROMBOPHLEBITIS & THROMBOEMBOLISM IN ... SUPERFICIAL & DEEP VEINS. /ESTROGENS/

PULMONARY EMBOLISM, CEREBRAL EMBOLISM WITH STROKE & MESENTERIC VASCULAR OCCLUSION OCCUR. CORONARY THROMBOSIS ... INCR ... ALTER HEPATIC FUNCTION, WHICH ... ALTER ... TESTS OF LIVER FUNCTION AS WELL AS VARIOUS SYNTHETIC & BIOTRANSFORMATION PROCESSES. ... DECR IN GLUCOSE TOLERANCE, & DIABETES MELLITUS MAY BE EXACERBATED. /ESTROGENS/

For more Human Toxicity Excerpts (Complete) data for DIENESTROL (21 total), please visit the HSDB record page.

35 FEMALE VIRGIN CC57W MICE RECEIVED DIENESTROL ... IN TAMPONS /1-2 TIMES/WK IN VAGINA ... . OF 28 CASES OF HYPERPLASIA OF OVARIAN GRANULOSA CELLS, 15 WERE ... OVARIAN TUMORS ... . PAPILLOMAS OF VAGINA WERE FOUND IN 29/29 TREATED MICE & IN 28/41 CONTROLS ... .

125 FEMALE GUINEA PIGS (65 OVARIECTOMIZED & 60 INTACT) WERE GIVEN DV SC IN DAILYDOSES OF 1 MG/KG BODY WT. ... UTERINE LEIOMYOMAS WERE FOUND ... IN 8/23 ... KILLED ... AFTER 31-60 DAYS, IN 12/18 ... KILLED ... 61-90 DAYS & IN 12/25 ... KILLED AFTER 90 DAYS ... . NO TUMORS ... IN ... 20 INTACT & 20 OVARIECTOMIZED ... .

In certain animal species, long term, continuous systemic administration of estrogens increases the frequency of cancers of the breast, cervix vagina, and liver. /Estrogen/

A series of nine chemicals of varying structure and estrogenicity was investigated for biochemical determinants of their relative capacities to alter normal embryonic growth and developmental patterns during organogenesis in rats. In order to circumvent the potentially confounding influences of maternal factors, the direct effects of steroidal and nonsteroidal estrogens on cultured whole embryos were compared at concentrations producing readily measurable embryotoxicity but low embryolethality (2-20%). Nonsteroidal estrogens included were diethylstilbestrol, hexestrol, E,E-dienestrol, and tamoxifen. Steroidal estrogens were estradiol 17 beta, estrone, and 17 alpha-ethinylestradiol 17 beta. For comparative purposes, the effects of two essentially nonestrogenic phenols, Z,Z-dienestrol and phenol, were also studied. Tamoxifen, a weak estrogen which also exhibits antiestrogenic properties, was studied for possible interactive effects with potent estrogens. Prosencephalic hypoplasia was the abnormality most consistently observed and was elicited by each of the chemicals investigated. Embryotoxicity was neither attenuated by tamoxifen nor related to estrogenic potency or steroidal structure, but was strongly and unpredictably influenced by biotransformational determinants. Presence of a cytochrome p450 dependent oxidizing system in the culture medium resulted in marked increases in embryotoxicity of estrone, estradiol 17 beta, and phenol, only minor increases for Z,Z-dienestrol and E,E-dienestrol, but in strikingly decreased effects of 17 alpha-ethinylestradiol 17 beta, tamoxifen, and hexestrol. It produced no statistically significant differences in effects of diethylstilbestrol. The results obtained were compatible with the concept that effects of these agents on growth and development during the earlier stages of organogenesis are independent of steroid structure or estrogenic activity but strongly dependent upon pathways and rates of biotransformation of some (but not all) of the parent chemicals.

For more Non-Human Toxicity Excerpts (Complete) data for DIENESTROL (6 total), please visit the HSDB record page.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl dienestrol, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act.

G - Genito urinary system and sex hormones

G - Genito urinary system and sex hormones

QG - Genito urinary system and sex hormones

QG - Genito urinary system and sex hormones

Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include 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. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).

Dienestrol is a synthetic, non-steroidal estrogen. Estrogens passively diffuse into target cells of responsive tissues, complex with the estrogen receptors, and enter the cell's nucleus to initiate or enhance gene transcription of protein synthesis after binding to DNA.

ESTROGENS ARE FIRST BOUND WITH VERY HIGH AFFINITY TO A CYTOPLASMIC 8 S RECEPTOR PROTEIN, WHICH THEN DISSOCIATES INTO A 4 S WITH ESTROGEN ATTACHED. ... THE ESTROGEN COMPLEX IS CONVERTED TO A 5 S SPECIES THAT IS TRANSPORTED TO THE NUCLEUS, WHERE ULTIMATE BINDING OF ESTROGEN-CONTAINING COMPLEX OCCURS. /ESTROGENS/

THE ACTIVITY OF ... SYNTHETIC ... ESTROGENS DEPENDS ON PRESENCE OF HYDROXYL GROUPS @ EXTREMITIES OF THEIR MOLECULES ... HYDROXYLS ... INVOLVED IN BINDING WITH SPECIFIC RECEPTOR PROTEINS, PRESENT IN CYTOSOL OF CELLS IN TARGET ORGANS. /ESTROGENS/

At the cellular level, estrogens increase the cellular synthesis of DNA, RNA, and various proteins in responsive tissues. Estrogens reduce the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, leading to a reduction in release of follicle-stimulating hormone and luteinizing hormone from the pituitary. /Estrogen/

Hepatic.

DIENESTROL YIELDS DIENESTROL-BETA-D-GLUCURONIDE IN RABBITS.

DIENESTROL IS A KNOWN METABOLITE OF DIETHYLSTILBESTROL IN PRIMATES & MICE; IT IS CONVERTED TO OMEGA-HYDROXY-DIENESTROL, WHICH IS EXCRETED IN CONJUGATED FORM ... RABBITS GIVEN ORAL DOSES OF DIENESTROL EXCRETED DIENESTROL GLUCURONIDE IN THEIR URINE ... .

RABBITS GIVEN ORAL DOSES OF DIENESTROL EXCRETED DIENESTROL GLUCURONIDE IN THEIR URINE ... .

Systemic absorption and mode of action of dienestrol are undetermined.Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include 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. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).

ESTROGENS USED IN THERAPY ARE ... READILY ABSORBED THROUGH SKIN, MUCOUS MEMBRANES, AND GI TRACT. WHEN THEY ARE APPLIED FOR LOCAL ACTION, ABSORPTION IS OFTEN SUFFICIENT TO CAUSE SYSTEMIC EFFECTS. /ESTROGENS/

IN FACTORY WORKERS GYNECOMASTIA HAS FOLLOWED HANDLING OF DIETHYLSTIBESTROL WITHOUT GLOVES. /DIETHYLSTILBESTEROL/

URINARY EXCRETION RATE OF ESTROGENS IS QUITE SIMILAR WHETHER AGENTS ARE GIVEN ORALLY OR INTRAVENOUSLY, WHICH SUGGESTS THAT ABSORPTION OF MOST ESTROGENS FROM GI TRACT IS PROMPT & QUITE COMPLETE. /ESTROGENS/

ESTROGENS ARE PRACTICALLY INSOLUBLE IN WATER. WHEN DISSOLVED IN OIL AND INJECTED, THEY ARE RAPIDLY ABSORBED & QUICKLY METABOLIZED. ... INACTIVATION OF ESTROGEN IS CARRIED OUT MAINLY IN THE LIVER. /ESTROGENS/

For more Absorption, Distribution and Excretion (Complete) data for DIENESTROL (10 total), please visit the HSDB record page.

MEDICATION (VET)

MEDICATION

FARMACYROL, LIPAMONE, RETALON-ORAL /DIENESTROL DIACETATE/

Grade: National Formulary

Vaginal Cream: 0.01%, DV, Marion Merrall Dow; Ortho Dienestrol, Ortho.

DOSAGE FORMS-- CREAM NF: 0.01%; SUPPOSITORIES: 0.7 MG; TABLETS NF: 100 & 500 MCG.

DIENESTROL IS NOT KNOWN TO OCCUR NATURALLY.

... DO NOT ADMIN TO LAYING BIRDS OR BREEDING FLOCKS. AVOID CONTAMINATION WITH FEED OR WATER SUPPLY TO OTHER LIVESTOCK OR HUMANS.

Dienestrol is a synthetic nonsteroidal estrogen. The drug is structurally similar to diethylstilbestrol but differs structurally from diethylstilbestrol in the substitution of two unsaturated ethylidene groups for the two diethyl groups of diethylstilbestrol.