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HCID 5991Erstellt: 27. Oktober 2026

Ethinylestradiol

ETHINYL ESTRADIOL · ETHYNYLESTRADIOL · 17α-Ethynylestradiol · 17α-Ethinylestradiol · Estradio · 17a-ethinylestradiol · eed · 17ALPHA-ETHYNYLESTRADIOL

https://huagongshe.com/de/chemical/5991

Molekülstruktur von Ethinylestradiol

Identifikatoren & physikalische Daten

CAS No.57-63-6
SummenformelC20H24O2
Durchschnittliche Molmasse296,4 g/mol
Monoisotopische Masse296,17763001 g/mol
SMILESC#C[C@]1(O)CC[C@H]2[C@@H]3CCc4cc(O)ccc4[C@H]3CC[C@@]21C
InChIKeyBFPYWIDHMRZLRN-SLHNCBLASA-N
PubChem CID5991
ChEMBLCHEMBL691
ChEBICHEBI:4903
EC No.200-342-2
DTXSIDDTXSID5020576
Lokaler NameEthinylestradiol

Chemische & physikalische Eigenschaften

XLogP3,7
Polarare Oberfläche (TPSA)40,5
H-Brücken-Donoren2
H-Brücken-Akzeptoren2
Frei drehbare Bindungen1
Schwere Atome22
Formalladung0
Komplexität505
StoffklassenHormone and(or) waste-water effluent contaminant
ArzneimittelPharmaceuticals -> Listed in ZINC15
LipideLipids -> Sterol Lipids [ST] -> Steroids [ST02] -> C18 steroids (estrogens) and derivatives [ST0201]
LogP (Verteilungskoeffizient)log Kow = 3.67
GeruchOdorless
Color/FormFine, white to creamy white crystalline powder
Löslichkeitless than 1 mg/mL at 70 °F (NTP, 1992)Solubility: 1 part in 6 of ethanol, 1 in 4 of ether, 1 in 5 of acetone, 1 in 4 of dioxane, and 1 in 20 of chloroform. Soluble in vegetable oils, and in solutions of fixed alkali hydroxides.Soluble in solutions of sodium hydroxide or potassium hydroxideIn double-distilled water, 4.83 mg/LIn water, 11.3 mg/L at 27 °Cethanol: 50 mg/mL, clear, slightly yellow
Human DrugsBreast FeedingLactationMilk, HumanEstrogensEstrogenic Steroids, AlkylatedFDA approved drugs -> Active ingredientPharmaceuticals
Endocrine DisruptorsPotential endocrine disrupting compound
DecompositionWhen heated to decomposition it emits acrid smoke and irritating fumes.
Schmelzpunkt288 to 295 °F (NTP, 1992)142-144142-146 °C. May also exist in a polymorphic modification with mp 180-186 °C183 °C182-183 °C(lit.)
Optical RotationFine needles from methanol and water, mp 141-146 °C. Specific optical rotation: 1 deg at 25 °C/D (dioxane). Dehydrates after melting and further heating /Ethinyl estradiol hemihydrate/Specific optical rotation: 3.5 deg at 24 °C/D (c = 2 in dioxane)-29.5 deg at 24 °C/D (c = 2 in pyridine)Slightly dextrorotatory in dioxane solution
Siedepunkt378°C (rough estimate)
Dichte1.0944 (rough estimate)
Brechungsindex-30 ° (C=0.4, Pyridine)
Flammpunkt9℃
Lagerbedingungenroom temp
pKa (Säurekonstante)pKa 10.32 (Uncertain)
AggregatzustandSolid
FarbeWhite to Light yellow to Light orange
Biologische Quellesynthetic
Merck14,3734
BRN2419975
Henry-Konstante1.2×106 mol/(m3Pa) at 25℃, HSDB (2015)
BCS Class3/1
Hauptanwendungenclinical testing
Kosmetik-Inhaltsstoffe FunktionenSKIN CONDITIONING
InChI1S/C20H24O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,5,7,12,16-18,21-22H,4,6,8-11H2,2H3/t16-,17-,18+,19+,20+/m1/s1
InChIKeyBFPYWIDHMRZLRN-SLHNCBLASA-N
SMILES[H][C@]12CC[C@@]3(C)[C@@]([H])(CC[C@@]3(O)C#C)[C@]1([H])CCc4cc(O)ccc24
CAS Datenbank57-63-6(CAS DataBase Reference)
NIST chemische InformationenEthinyl estradiol(57-63-6)
EPA chemische InformationenEthinyl estradiol (57-63-6)

Sicherheit & Vorschriften

GHS-EinstufungDangerH302 (63%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P264, P270, P273, P280, P301+P317, P318, P319, P330, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 108 reports by companies from 16 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Regulatorische InformationenHazard Traits - CarcinogenicityEthinylestradiol: Does not have an individual approval but may be used under an appropriate group standard
Weitere SicherheitsinformationenIMAP assessments - 19-Norpregna-1,3,5(10)-trien-20-yne-3,17-diol, (17.alpha.)-: Environment tier I assessment
BrandgefahrenThe flash point data for this compound are not available. It is probably combustible. (NTP, 1992)
GesundheitsgefahrenACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits acrid smoke and fumes. (NTP, 1992)
FDA-AnforderungenThe Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including ethinyl estradiol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Reaktive GruppeAlcohols and Polyols
Reactivity ProfileETHINYLESTRADIOL may react vigorously with strong oxidizing agents. May react exothermically with reducing agents to generate gaseous hydrogen.
Air and Water ReactionsAir and light sensitive (NTP, 1992). Insoluble in water.
Hazard Classes and CategoriesAcute Tox. 4 (63%)
BrandbekämpfungFires involving this compound can be controlled with a dry chemical, carbon dioxide or Halon extinquisher. (NTP, 1992)
Erste HilfeEYES: 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.

Anwendungen & Verwendung

Beschreibung

Estrogens direct the development of the female genotype in embryogenesis and at puberty. Estradiol is the major estrogen secreted by the premenopausal ovary. Ethynyl estradiol is a synthetic analog of 17β-estradiol . A USP-approved grade of ethynyl estradiol is often formulated in combination with a progestin such as norgestrel /levonorgestrel or desogestrel and provided for use as an oral contraceptive. Efficacy of oral administration of ethynyl estradiol is facilitated by the ethynyl substitution at the C-17 position, which inhibits first pass hepatic metabolism. Ethynyl estradiol is also rapidly and almost completely absorbed from the gastrointestinal tract.

Verwenden

A metabolite of 17a-Ethynylestradiol

Freisetung ohne BrandSMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol 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.
EntsorgungsverfahrenSRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.
Personal Protective Equipment (PPE)RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)
WechselwirkungenEstrogens may interfere with the effects of bromocriptinedosage adjustment may be needed. /Estrogens/Concurrent use /of calcium supplements/ with estrogens may increase calcium absorption and exacerbate nephrolithiasis in susceptible individualsthis can be used to therapeutic advantage to increase bone mass. /Estrogens/Concurrent use /of glucocorticoid corticosteroids/ with estrogens may alter the metabolism and protein binding of the glucocorticoids, leading to decreased clearance, increased elimination half-life, and increased therapeutic and toxic effects of the glucocorticoidsglucocorticoid dosage adjustment may be required during and following concurrent use. /Estrogens/Concurrent use /of corticotropin (chronic therapeutic use)/ with estrogens may potentiate the anti-inflammatory effects of endogenous cortisol induced by corticotropin. /Estrogens/For more Interactions (Complete) data for ETHINYLESTRADIOL (15 total), please visit the HSDB record page.
ÖkotoxizitätswerteEC50Species: Danio rerio (Zebra danio, age 6-8 month adult, female)Conditions: freshwater, renewal, 25-28 °C, pH 8.0-8.5, hardness 140-145 mg/L CaCO3Concentration: 0.027 nM for 3 weeksEffect: morphology, decreased ovarian weight in relationship to body weight /98% purity/Species: Pimephales promelas (Fathead Minnow, eggs)Conditions: freshwater, flow throughConcentration: 0.00166 ug/L for 44 weeksEffect: population growth rate /100% purity 17alpha-ethynylestradiol/LC50Species: Danio rerio (Zebra danio, ~9 month adult, weight 0.8 g, length 4.3 cm)Conditions: freshwater, static, 24 °C, pH 7.8, hardness 350 mg/L CaCO3Concentration: 1700 ug/L for 96 hr /98% purity 17alpha-ethynylestradiol/Species: Rana pipiens (Leopard frog, tadpole, weight 0.020-0.025 g)Conditions: freshwater, renewalConcentration: 2.75 uM for 2 weeks /100% purity/For more Ecotoxicity Values (Complete) data for ETHINYLESTRADIOL (11 total), please visit the HSDB record page.
UmweltverhaltenTERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 510(SRC), determined from a log Kow of 3.67(2) and a regression-derived equation(3), indicates that ethinylestradiol is expected to have low mobility in soil(SRC). Volatilization of ethinylestradiol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.9X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Ethinylestradiol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.9X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Ethinylestradiol has been classified as not readily biodegradable using a sewage inoculm(6), indicating that biodegradation may not be an important environmental fate process in soil(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 510(SRC), determined from a log Kow of 3.67(2) {and a regression-derived equation(3), indicates that ethinylestradiol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 7.9X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 110(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). Ethinylestradiol has been classified as not readily biodegradable using a sewage inoculm(7), indicating that biodegradation may not be an important environmental fate process in water(SRC).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ethinylestradiol, which has an estimated vapor pressure of 1.9X10-9 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 ethinylestradiol may be removed from the air by wet or dry deposition(SRC). Ethinylestradiol absorbs light at wavelengths 281 nm(4), and therefore may be susceptible to direct photolysis by sunlight(SRC).
ExpositionspfadeRapid and complete absorption follows oral intake of ethinyl estradiol (bioavailability 43%).
ToxizitätsübersichtIDENTIFICATION: Ethinylestradiol is a synthetic steroid, prepared from estrone. It is a white to creamy or slightly yellowish-white powder or crystals. It is insoluble in water, soluble in ethanol. Indications: The most frequent use is as the estrogen component of combined oral contraceptives. Also used for the treatment of menopausal and post menopausal symptoms, especially the vasomotor effects. Used in the treatment of female hypogonadism and as a palliative treatment in malignant neoplasm of breast and prostate. Also used in the treatment of some women with acne, and in Turner's syndrome. HUMAN EXPOSURE: Main risks and target organs: Acute poisoning with ethinylestradiol results in mild, self limiting effects, usually involving the gastrointestinal tract. Chronic toxicity increases the risk of cardiovascular disease, including myocardial infarction, cerebrovascular disease, thromboembolic disease, gallbladder disease, and certain cancers in some people. Summary of clinical effects: Acute poisoning with ethinylestradiol is mild and self limiting. Nausea, vomiting and occasionally vaginal breakthrough bleeding may occur. Chronic toxicity from ethinylestradiol, like other estrogens, increases the risk for stroke, myocardial infarction and thromboembolic disease in certain populations. Jaundice, hypertension, nasal congestion, headache, dizziness and fluid retention may occur. Endometrial, breast, and certain liver cancers may occur at a higher incidence than the general population. Contraindications: Contraindications are those of the use of estrogens in general, and include the following: Known or suspected carcinoma of the breast, except in selected patients being treated for metastatic disease. Known or suspected estrogen dependent neoplasia. Known or suspected pregnancy. Undiagnosed abnormal genital bleeding. Active thrombophlebitis or thromboembolic disease. A past history of thrombophlebitis, thrombosis or thromboembolic disease associated with the previous use of estrogen containing compounds. Absorption by route of exposure: Ethinylestradiol is rapidly and completely absorbed from the gastrointestinal tract. The ethinyl substitution in the C17 position inhibits first-pass metabolism. Bioavailability is reported at 40%. Distribution by route of exposure: Extensively plasma protein bound, mainly to albumin. Unbound molecules distribute widely in the tissues due to their lipophilic nature. Peak plasma concentrations occur initially at 2 to 3 hours after oral ingestion. A second, 12 hour peak, is thought to represent extensive enterohepatic circulation. Biological half-life by route of exposure: Biological half life is approximately 7.7 hours following a single oral therapeutic dose. Elimination phase half life is reported between 13 and 27 hours. Metabolism: Compared to other estrogens, metabolism is slow. Primary route of biotransformation is via 2-hydroxylation and the formation of 2- and 3-methyl ethers. First-pass metabolism occurs primarily in the gut wall. Elimination by route of exposure: Some enterohepatic circulation of sulfate and glucuronide metabolites does occur, hence some is excreted via the feces. Excretion is also via the kidneys. Mode of action: Toxicodynamics: 2 to 3 fold increase in the incidence of gallbladder disease is reported with the use of estrogens. This is thought due to an increased saturation of bile with cholesterol and a reduction of bile acid secretion. Also, many studies have been performed investigating the adverse effects of estrogens, including ethinylestradiol, on coagulation. These have used estrogens alone, and estrogens in combination with progestins. However a consensus of the net outcome of physiologic or pharmacological doses has not occurred as yet. Pharmacodynamics: Like other steroid hormones, ethinylestradiol is thought to act primarily through the regulation of gene expression. As a lipophilic hormone, it diffuses readily through cellular membranes to bind to estrogen receptors situated in the nucleus. Estrogen receptors are found in the female reproductive tract, breast, pituitary, hypothalamus, bone, liver and other tissues. The receptor interacts with a specialized nucleotide sequence, resulting in either an increase or decrease in the transcription of hormone regulated genes. Tissues may vary in the way in which they respond to receptor activation. Desirable therapeutic effects, include its action on the female reproductive tract, (usually in combination with a progesterone), where ethinylestradiol stimulates proliferation and differentiation in the fallopian tube, and increase the tubal muscular activity. Ethinylestradiol also increases the water content of cervical mucus and favors contraction of the uterine myometrium. Estrogens, including ethinylestradiol, block resorption of bone, resulting in a positive effect on bone mass. It is well established that the risk of endometrial hyperplasia and cancer is increased in women receiving unopposed estrogen replacement therapy, including ethinylestradiol. Data from the 1970's and 1980's reported a 2 to 15 fold increase in the risk of endometrial carcinoma. The higher the dose and the longer the length of therapy the greater the risk. However, the addition of progestogen to estrogen replacement therapy was protective. More research is needed before a conclusion can be drawn on whether ethinylestradiol therapy, and other estrogens, increase the risk of breast carcinoma. Conflicting findings have been reported. A review of data from the 1970's and 1980's suggests that there is a moderate increase in the risk of breast carcinoma, but this did not occur until after 5 years of therapy. Teratogenicity: No specific data available for ethinylestradiol. Reports suggest a link between fetal exposure to female sex hormones and congenital abnormalities. These include heart defects, and limb defects. Other estrogens, namely diethylstilbestrol, have been associated with the development of vaginal and cervical adenocarcinoma in female offspring of mothers who had taken this drug during the first trimester. Diethylstilbestrol ingestion during pregnancy is also associated with a number of other abnormalities in male offspring, including, smaller testes and urogenital abnormalities. Although no studies relating ethinylestradiol directly to these findings were identified, the pharmacological similarities in this class of compounds suggest caution should be used. Main adverse effects: The main adverse effects of ethinylestradiol given in therapeutic dose are directly related to its estrogenic and metabolic effects. They include water and sodium retention, which may result in edema, weight gain and tender breast enlargement. Changes in libido, and withdrawal vaginal bleeding is also reported. Liver function impairment, jaundice and gallstones may occur. Headache, depression, dizziness, glucose intolerance, and a sensitivity to contact lenses are described. Large doses may produce hypercalcemia when used in the treatment of metastatic carcinoma. Nausea, vomiting and diarrhea are not uncommon. Dermatological effects include chloasma, melasma, rashes and urticaria. Erythema multiforme and erythema nodosum occur. Hypertension and thromboembolic disease are reported. Acute poisoning: Ingestion: Acute poisoning effects are mild and self limiting. Nausea, vomiting and break through vaginal bleeding have been reported following oral contraceptive overdose. Nasal congestion, visual disturbances, headache and hypertension have also been reported in association with estrogen overdose. ANIMAL/PLANT STUDIES: Relevant animal data: A correlation between the prolonged use of oral contraceptives and the development of liver cancer was demonstrated in rats. Induced DNA breaks in hamster kidneys, but not in livers, following 2 weeks of treatment with a single estradiol implant. Tumors of kidney, bone, testis, uterus and breast, were induced in animals exposed to estrogens. Mutagenicity: Estradiol induced DNA breaks in hamster renal cells, but not in hepatocytes.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. This cascade is initiated by initially binding to the estrogen receptors. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).
Ökotoxizitätsauszüge/BIRDS and MAMMALS/ Very low-density apolipoprotein II (apoVLDL) is one of the constituents of yolk in avian eggs. The expression of the apoVLDL gene is highly specific to the liver in mature female birds during the egg-laying period but is stimulated by exogenous estrogens in immature male birds. In the present study, we compared the effects of two estrogenic compounds, diethylstilbestrol and ethinylestradiol, on the expression of apoVLDL mRNA in the liver of Japanese quail (Coturnix japonica). Three-week-old, immature male quail were treated with a single intraperitoneal injection of the estrogenic compounds, and the level of apoVLDL mRNA in the liver was measured by gene-specific real-time polymerase chain reaction. Diethylstilbestrol and ethinylestradiol had a similar effect on the level of mRNA, increasing it in a dose-dependent manner. Next, the levels of apoVLDL mRNA in the liver of male embryos, which were developed in fertile eggs laid by quail injected with the estrogenic compounds during yolk formation, were measured. Maternal exposure to ethinylestradiol caused an increase in the mRNA in embryos, whereas exposure to diethylstilbestrol had no effect. These results point out the importance of the route of administration to the evaluation of the estrogenic effects of endocrine disruptors in oviparous species./AQUATIC SPECIES/ The aim of this study was to investigate the effect of the most potent xenoestrogen currently found in the environment, ethinylestradiol (EE2), on some physiological events occurring during early spermatogenesis of gudgeon (Gobio gobio), a common European fish species. Physiological pathways studies were apoptosis, cell proliferation, and steroidogenesis on sex steroids (testosterone [T], 11-ketotestosterone [11-KT], and 17beta-estradiol [E2]). Testis pieces were cultured in vitro during 21 d at 10(-4), 10(-3), 10(-2), 10(-1), 1 and 10 ug/L of EE2 as well as in positive (10(-1) ug/L of E2) and ethanol control medium. Apoptosis and cell proliferation displayed opposite responses related to the EE2 concentration. When apoptosis inhibition was observed, cell proliferation was induced at 10(-2) and 10(-1) ug/L of EE2 as well as in the positive control. In contrast, a massive cell death was detected for high EE2 concentrations (1 and 10 ug/L). Steroidogenesis was also disrupted in a dose-related manner. 11-Ketotestosterone was depressed at 10(-2) and 10(-1) ug/L of EE2 whereas E2 was detectable in the medium only at 10(-3), 10(-2), and 10(-1) ug/L of EE2. High concentrations of T were detected in the medium at 10(-3), 10(-2), and 10(-1) ug/L of EE2 but depressed at 1 and 10 ug/L of EE2. In conclusion, intermediate EE2 concentrations (10(-2) and 10(-1) ug/L) used in this experimental design have obviously disrupted early spermatogenesis, leading to an imbalance between cell death and cell proliferation in a sex steroid environment toward E2. The results of the present study could be the basis conditions for oocyte development within the testis of a common teleost fish under xenoestrogen exposure./AQUATIC SPECIES/ Until now, studies dedicated to the actions of endocrine disrupting chemicals (EDCs) on the reproductive axis have been concerned with their effects at the gonadal level leaving their actions on neuroendocrine circuits controlling reproduction virtually unexplored. In vertebrates, gonadotropin-releasing hormone (GnRH) is the key factor controlling the activity of the reproductive axis. The development and functioning of GnRH neurons are finely tuned by a series of factors, notably sex steroids, making these neurons potential targets of EDCs, notably in aquatic species. By means of immunohistochemistry, /investigators/ examined the effects of low levels of ethinylestradiol (EE2 0.02 nM, 0.1 nM, 0.5 nM), a potent synthetic estrogen, on early development (at 5, 10, 20, 30 days post-fertilization) of the forebrain GnRH neurons in a model fish species, the zebrafish (Danio rerio). In parallel, the ER-regulated expression of cytochrome P450 aromatase B (AroB) protein, which is encoded by the cyp19a1b gene, was precisely mapped at the brain and pituitary levels in developing control and EE2-exposed zebrafish. /Investigators/ show that EE2 disrupts the ontogeny of GnRH system by inducing an increase in the number of GnRH-ir neurons and GnRH fibers based on their immunoreactivity as well as a decrease in the size of the GnRH-ir soma and a modification of the migration profile of GnRH-ir neurons. Furthermore, /the authors/ report a spectacular dose and time-dependent induction of AroB expression in radial glial cells of the developing brain further illustrating the extreme sensitivity of AroB to xenoestrogen and the relevance of AroB as biomarker of xenoestrogen effects on the central nervous system. Collectively, these original and relevant observations highlight the sensitivity of GnRH and AroB to a synthetic estrogen during embryogenesis. These data reinforce the need to further study the mechanisms underlying EDC effects on key neuroendocrine circuits involved in reproduction and brain development of vertebrates./AQUATIC SPECIES/ ... The present study aimed at examining the effects of EE2 on the full embryonic development of zebrafish in order to identify the actual phases where EE2 disrupts this process. Hence, zebrafish were exposed to environmentally relevant low levels of EE2, 0.5, 1 and 2 ng/L (actual concentrations of 0.19, 0.24 and 1 ng/L, respectively) from egg up to eight months of age (F(1)), and the survival as well as the occurrence of abnormalities in their offsprings (F(2)), per stage of embryonic development, was investigated. A thorough evaluation of reproductive endpoints and transcription of vtg1 gene in the parental generation (F(1)) at adulthood, was performed. No significant differences could be observed for the two lowest EE2 treatments, in comparison with controls, whereas vtg1 transcripts were significantly elevated (40-fold) in the 2ng/L EE2 treatment. In contrast to the findings in the F(1) generation,a significant concentration-dependent increase in egg mortality between 8 and 24hours post-fertilization (hpf) was observed for all EE2 treatments, when compared with controls. The screening of egg and embryo development showed a significant increase in the percentage of abnormalities at 8 hpf for the highest EE2 concentration, a fact that might explain the increased embryo mortality at the 24 hpf time-point observation. Taken together, these findings indicate that the two lowest tested EE2 concentations impact late gastrulation and/or early organogenesis, whereas exposure to 2ng/L EE2 also disrupts development in the blastula phase. After early organogenesis has been completed (24 hpf), no further mortality was observed. These results show that increased embryo mortality occurs at EE2 levels below those inducing reproductive impairment and vtg1 gene induction in the male parental generation, thus suggesting that EE2 may impact some fish populations at levels below those inducing an increase in vtg1 transcripts. Hence, these findings have important implications for environmental risk assessment, strongly supporting the inclusion of embryonic development studies in the screening of endocrine disruption in wild fish populations.For more Ecotoxicity Excerpts (Complete) data for ETHINYLESTRADIOL (17 total), please visit the HSDB record page.
Signs and SymptomsSymptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females. The FDA label includes a black box warning that states that combination oral contraceptives with ethinyl estradiol should not be used in women over 35 years old who smoke due to the increased risk of serious cardiovascular side effects.
Ongoing Test StatusThe following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=57-63-6]
Effluent ConcentrationsFor ethinylestradiol, a concentration range of 0.50 to 2.52 ug/L was reported as a result of analysis of raw sewage entering 14 representative sewage plants within a 50-mile radius of Cincinnati, OHthe average concentration was 1.21 ug/L. The treated effluent concentration range was 0.28 to 0.98 ug/L, average 0.55 ug/L(1). A concentration of 0.0045 ug/L has been reported in effluent from a Swedish sewage treatment plant(2). The mean ethinylestradiol concentration in effluent samples from a large coastal primary sewage treatment plant in Malabar, Sydney, Australia was <5 ng/L(3). Concentrations in sewage treatment plant effluents were as follows: Italy, 10/99-03/2000, 30 samples, <detection limit-1.7 ng/L (0.45 ng/L median)Netherlands, 10/97-12/97, 6 samples, <0.2-7.5 ng/L (<etection limit median)Germany, 11/97, 16 samples, <detection limit-15 ng/L (1 ng/L median)Canada, 11/97, 10 samples, <detection limit-42 ng/L (9 ng/L median): UK, 5/95-1/96, 21 samples, <detection limit-7 ng/L (<detection limit median)USA, 05/97-10/97, 5 samples, <detection limit-0.759 ng/L (0.248 ng/L median)Germany, 6/2000-10/2000, 16 samples, <0.10-8.9 ng/L (0.7 ng/L median)(4). Ethinylestradiol was detected at concentrations of <4.0 (July 2003), <2.0 (Sept 2003, and <2.0 ng/L (Feb 2004) in effluent from the Eysines Sewage Treatment Plant (northern suburbs, Bordeaux, France) and runs through agricultural and residential areas(5). Ethinylestrdaiol was not detected in influent samples to the Piera and Igualada sewage treatment plants, respectively, on the Anoia tributary in the vicinity of Barcelona, Spain, sampled from April to June, 1999(6). Ethinylestradiol was detected in 9 of 38 German municipal sewage treatment plant effluents at a 90-percentile concentration of 0.001 ug/L, maximum 0.015 ug/L(7). The compound was detected in 14 of 16 effluent samples collected from Ulm, Langenau, and Blaubeuren, southern Germany between June to October 2000 at concentrations ranging from 0.1 to 8.9 ng/L, median 1.4 ng/L(8).
Soil Adsorption/MobilityThe Koc of ethinylestradiol is estimated as 510(SRC), using a log Kow of 3.67(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that ethinylestradiol is expected to have low mobility in soil. A Freundlich adsorption coefficient, log Kd, of 1.72 has been measured(4). The compound was not detected in the effluent of a 23-day column drainage study using Mahall-Laveen sandy loam soil from an area northwest of Phoenix, AZ and 200 L of treated effluent from a municipal waste treatment facilityreporting limit = 0.005 ug/L(5), suggesting adsorption to soil in the column(SRC). A Kd of 584 L/kg was reported using activated sludge(6). Ethinylestradiol was 98.6%, 99.3%, and 96.4% removed from wastewater final effluent by coal-based, coconut-based, and wood-based granular activated carbon, respectively. COD at an equilibrium concentration of 7 mg/L were 3.16, 4.8, and 71 mg/g, respectivelyhowever, adsorption capacities were reduced in the presence of other competing adsorbates(7).
Human Toxicity Excerpts/CASE REPORTS/ ... A 28-year-old female with a medical history positive for acne had been taking Minidril since January 2008 and isotretinoin for acne since July 2008. On December 18, 2008, laboratory tests performed before a dermatologic visit revealed elevated alanine aminotransferase (ALT) levels of 226 U/L, 7 times the normal level (reference range <31)aspartate aminotransferase (AST) 93 U/L, 3 times the normal level (<31)gamma-glutamyl transferase 37 U/L (7-35)and alkaline phosphatase (ALP) 92 U/L (35-120). Total bilirubin was 0.23 mg/dL (<1.0) and prothrombin time was 97%there was no peripheral blood eosinophilia. At that time, transaminase elevation was believed to be related to isotretinoin, a vitamin A derivative, which was discontinued 4 days later, on December 22. Additional laboratory tests performed later revealed persistence of transaminase elevation, with progressive aggravation. On March 2, 2009, the patient was hospitalized for evaluation of hepatic function. She was afebrile and had normal vital signs. Her physical examination was unremarkable. She had no rash, no jaundice, and no pruritus. She denied any consumption of alcohol or over-the-counter acetaminophen. She had never received blood transfusions. She denied taking any medications, including herbal and folk remedies, other than Minidril. There was no recent travel history. Results of viral serologies for hepatitis including hepatitis A, B, C, D, and E virusescytomegalovirusEpstein-Barr virusHIVand herpes simplex virus were all negative. Tests for autoantibodies (antinuclear, antimitochondrial, anti-smooth muscle, anti-liver and antikidney microsomal antibodies, and anti-soluble liver antibodies) were also negative. Alpha 1-Anti-trypsin and ceruloplasmin values were within normal limits. Results of hepatobiliary imaging with ultrasonography, Doppler scan, and abdominal computed tomography scan were normal. Results of an endoscopic retrograde cholangiopancreatogram were also normal. Because no causal factor for cytolytic hepatitis was found after the initial work-up, an adverse effect caused by Minidril was suspectedconsequently, it was discontinued on March 6. Liver biopsy performed on March 2 found focal necrosis in peri- and centrolobular areas with ductular reaction compatible with drug-induced hepatitis. There was no sign of underlying chronic liver disease and no evidence of neoplastic or metabolic etiology. After Minidril discontinuation, hepatic enzymes rapidly decreased and became normal 1 month later./CASE REPORTS/ Although there are many cases of esophagitis related to pill in medical literature, there are only a few reports concerning esophagitis related to oral contraceptives, and none about cyproterone acetate and ethinylestradiol combination (Diane-35). In this report, /the authors/ describe a female patient who suffered from odynophagia and retrosternal pain after taking Diane-35 for hirsutism. The endoscopic examination revealed two well-demarcated circumferential ulcers of 1 cm diameter surrounded by relatively normal mucosa in mid-esophagus. The patient had gone to bed immediately after taking the pill. Oral intake was stopped, and intravenous fluids and omeprazole were administered as part of treatment. The patient benefited from this approach very quickly and was discharged from hospital in 5 days. The esophagus was completely normal in control endoscopy after 2 months. Diane-35 should be added to the list of drugs causing pill esophagitis, and physicians should inform the patients that the pills should be taken with enough water and they should not lie down right after ingesting the pills./CASE REPORTS/ High-dose estradiol therapy for reduction of final height may be complicated by severe side effects such as deep vein thrombosis. /Investigators/ report a 14.6-year-old girl with tall stature. In order to reduce final height she was treated with ethinylestradiol and medroxyprogesterone. After arthroscopy she suffered acute deep venous thrombosis of her left leg. Despite being monitored at short intervals, coagulation parameters such as AT III and protein C indicated no development of thrombosis. Medical height reduction with estrogen should be accompanied by heparinisation during longer-lasting periods of immobilisation./CASE REPORTS/ An 18-year-old woman presented with a large anterior myocardial infarction. Her cardiovascular risk factors were cigarette smoking in moderation and oral contraception with a synthetic oestroprogestative pill prescribed a few months previously. Coronary angiography showed occlusion of the left anterior descending artery but no other lesions. Biological investigations excluded an abnormality of coagulation. Antibodies to synthetic steroids (ethinylestradiol and progesterone) and circulating immune complexes were found in the serum. The role of antiethinylestradiol antibodies in the mechanism of myocardial infarction is discussed. These antibodies are present in 30 per cent of women taking oral contraceptives and their titres are significantly higher in 90 per cent of women who develop vascular thrombosis unrelated to atherosclerosis. The mechanism of the thrombogenic action of the antibodies and circulating immune complexes is also considered.For more Human Toxicity Excerpts (Complete) data for ETHINYLESTRADIOL (32 total), please visit the HSDB record page.
Artificial Pollution SourcesEthinylestradiol's production and use in combination with progestogen as oral contraceptive(1) may result in its release to the environment through various waste streams(SRC).
F8
Wassergefährdungsklasse (WGK)3
TSCA-Inventar-StatusTSCA listed
UN-TransportnummerUN1230 - class 3 - PG 2 - Methanol, solution
Zollcode29372390
RTECS-Nr.RC8925000
R-Sätze (R)45-22-39/23/24/25-23/24/25-11
ToxizitätLD50 oral in rat: 960mg/kg
GefahrensymboleT,F
Sicherheitshinweise (S)53-36/37/39-45-36/37-16
Gefahrenklasse9Acute Tox. 4 OralAquatic Chronic 1Carc. 2Repr. 1A
Lagerklasse6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
Gefahrstoffdaten57-63-6(Hazardous Substances Data)