| GHS classification | DangerH350 (39.6%): May cause cancer [Danger Carcinogenicity]P203, P260, P263, P264, P270, P273, P280, P318, P319, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 159 reports by companies from 19 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
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| Regulatory information | Hazard Traits - CarcinogenicityStatus: Active Update: 10-11-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/21288Oestradiol: Does not have an individual approval but may be used under an appropriate group standard |
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| Other safety information | IMAP assessments - Estra-1,3,5(10)-triene-3,17-diol, (17.beta.)-: Environment tier I assessment |
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| FDA requirements | Estradiol. For implantation in steers and heifers as follows: ... For increased rate of weight gain in suckling and pastured growing steersfor improved feed efficiency and increased rate of weight gain in confined steers and heifers.Estradiol valerate and norgestomet in combination. ... For synchronization of estrus/ovulation in cycling beef cattle and non-lactating dairy heifers. /Estradiol valerate and norgestomet in combination/Estradiol benzoate and testosterone propionate. ... For implantation in heifers as follows: ... For increased rate of weight gain and improved feed efficiency. /Estradiol benzoate and testosterone propionate/Progesterone and estradiol benzoate. Conditions of use in cattle. It is used for implantation as follows: (1) Suckling beef calves ... For increased rate of weight gain ... (2) Steers ... For increased rate of weight gain and improved feed efficiency ... (3) Steers fed in confinement for slaughter ... For additional improvement in rate of weight gain. /Progesterone and estradiol benzoate/For more FDA Requirements (Complete) data for ESTRADIOL (13 total), please visit the HSDB record page. |
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| Hazard Classes and Categories | Carc. 1A (39.6%) |
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| Hazardous Reactivities and Incompatibilities | A carcinogen. |
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| Storage conditions | Do not store unpouched. Apply immediately upon removal from the protective pouch.Store at controlled room temperature 15 to 30 °C (59 to 86 °F). |
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| Disposal methods | SRP: 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. |
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| Allowable Tolerances | No residues of estradiol, resulting from the use of estradiol or any of the related esters, are permitted in excess of the following increments above the concentrations of estradiol naturally present in untreated animals: (a) In uncooked edible tissues of heifers, steers, and calves: (1) 120 parts per trillion for muscle. (2) 480 parts per trillion for fat. (3) 360 parts per trillion for kidney. (4) 240 parts per trillion for liver. (b) In uncooked edible tissues of lambs: (1) 120 parts per trillion for muscle. (2) 600 parts per trillion for fat, kidney, and liver. |
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| Body burden | ... Human colostrum demonstrated a maximum concentration of about .5 ng/mL for estradiol. By the 5th day postpartum, it decreased to become similar to cow's milk. |
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| Interactions | Estrogens may interfere with the effects of bromocriptinedosage adjustment may be necessary. /Estrogens/A combination of testosterone and estradiol-B17 after treatment with methylnitrosurea also resulted in the development of adenocarciomas of the prostate.Concurrent use 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/For more Interactions (Complete) data for ESTRADIOL (11 total), please visit the HSDB record page. |
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| Ecotoxicity values | EC50Species: Daphnia magna (Water flea, age <24 hr neonate newly released)Conditions: freshwater, static, 20 °CConcentration: 1550 ug/L for 24 hr (95% confidence interval: 1050-2040 ug/L)Effect: development, decreased molting /100% purity, 17beta-estradiol/Concentration: 2040 ug/L for 48 hr (95% confidence interval: 1720-2360 ug/L)Concentration: 3670 ug/L for 24 hr (95% confidence interval: 3460-3880 ug/L)Effect: intoxication, immobilization /100% purity, 17beta-estradiol/Concentration: 2870 ug/L for 48 hr (95% confidence interval: 2670-3070 ug/L)For more Ecotoxicity Values (Complete) data for ESTRADIOL (14 total), please visit the HSDB record page. |
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| Environmental fate | TERRESTRIAL FATE: Based on a classification scheme(1), a Koc value of 30,000 indicates that estradiol is expected to be immobile in soil(SRC). Volatilization of estradiol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.6X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Estradiol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.4X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). A 6% mineralized of estradiol in 5 days after application to a agricultural soil microcosm(5) suggests biodegradation is not an important environmental fate process in soil(SRC).AQUATIC FATE: Based on a classification scheme(1), a Koc value of 30,000(2) indicates that estradiol is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.6X1011 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 200(SRC), from its log Kow of 4.01(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). A 6% mineralized of estradiol in 5 days after application to a agricultural soil microcosm(8) suggests biodegradation is not 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), estradiol, which has an estimated vapor pressure of 6.4X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist solely in the particulate phase in the ambient atmosphere. Particulate-phase estradiol may be removed from the air by wet or dry deposition(SRC). Estradiol irradiated with a xenon arc lamp exhibited a photodegradation half-life of 2 hours in river water and 41.7 hours in air-saturated purified water(3), and therefore estradiol may be susceptible to direct photolysis by sunlight(SRC). |
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| Adverse effects | Adverse effects are generally uncommonhowever, there have been reports of the following: |
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| Milk Concentrations | ENVIRONMENTAL: Free natural estrogens in raw and commercial whole milk were quantitated by radioimmunoassay. The concentration range of estradiol 17-beta was 4 to 14 pg/mL. The proportions of active estradiol in the fat phases of milk by radioactive tracer on separated milk was 65%. Equilibrium dialysis of skim milk with hydrogen 3-labeled estrogens showed that 84 to 85% of estradiol was protein bound. Whey proteins demonstrated a greater binding capacity than casein. This result was confirmed by radioimmunoassay of dry curd cottage cheese and whey. The concentration in curd was 11 pg/g and in whey 2 pg/mL. Butter was highest with a concentration of 82 pg/g. Human colostrum demonstrated a maximum concentration of 4 to 5 ng/mL for estriol. By the 5th day postpartum, it decreased to become similar to cow's milk.EXPERIMENTAL: Estrogens are excreted in milk. Potential for decreased milk volume and decreased nitrogen and protein content ...EXPERIMENTAL: Estrogen administration to nursing mothers has been shown to decrease the quantity and quality of the milk. Detectable amounts of estrogens have been identified in the milk of mothers receiving this drug. Caution should be exercised when Estradiol Transdermal System Continuous Delivery (Once-Weekly) is administered to a nursing woman. |
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| Toxicity summary | There are no published reports of estradiol toxicity in humans. However, one study measured estradiol toxicity in amphibians' embryos. Research determined that estradiol toxicity occurred when the amount of estradiol severely outnumbered estradiol receptorsthis was an incredibly high number that would be highly unlikely in a human population. Estradiol excess may lead to side effects and complications noted in the adverse effect section.Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. 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. |
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| Animal Concentrations | Mean estradiol concentrations of 2.70 and 4.36 ng/g dry weight were reported in eggs of the great crested grebe (Podiceps critatus) from Lakes Maggiore and Garda, respectively, northern Italy, sampled from 2001-2005(1). |
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| Signs and Symptoms | Can cause nausea and vomiting, and withdrawal bleeding may occur in females. |
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| Effluent Concentrations | 17beta-Estradiol was reported in 32% of 95-144 samples of central California municipal waste water treatment plant effluent with a maximum concentration of 7.8 ng/L(1). The compound was tested for but not detected (detection limit = 0.1 ng/L) in effluent samples collected from the Jefferson Parish East Bank Wastewater Treatment Plant in New Orleans, Louisiana between September and November, 2001. It was not detected in effluent samples collected during the same time from the A.H. Weeks Water Treatment Plant and the ENWIN Pilot Plant in Windsor, Ontario, Canada(2). Estradiol was not detected in effluent samples from wastewater treatment plants located on the West Prong Little Pigeon River in east Tennessee, USAdetection limit = 44 ng/L(3).A concentration of 0.0011 ug/L has been reported in effluent from a Swedish sewage treatment plant(1). The mean 17beta-estradiol concentration in effluent samples from a large coastal primary sewage treatment plant in Malabar, Sydney, Australia was 14 ng/L(2). Concentrations in sewage treatment plant effluents were as follows: Italy, 10/99-03/2000, 30 samples, 0.44-3.3 ng/L (1.0 ng/L median)Netherlands, 10/97-12/97, 6 samples, <0.1-5.0 ng/L (<detection limit median)Germany, 11/97, 16 samples, <detection limit-3 ng/L <detection limit median)Canada, 11/97, 10 samples, <detection limit-64 ng/L (6 ng/L median): UK, 5/95-1/96, 21 samples, 2.7-48 ng/L (6.9 ng/L median)Japan, 07/98-03/99, 27 triplicate samples, 3.2-55 (14 median)<detection limit-43 (13 median)0.3-30 (14 median) all values ng/LUSA, 05/97-10/97, 5 samples, 0.477-3.66 ng/L (0.9 ng/L median)Germany, 6/2000-10/2000, 16 samples, <0.15-5.2 ng/L (0.4 ng/L median)(3). 17beta-Estradiol 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 0.15 to 5.2 ng/L, mean 0.9 ng/L. 17alpha-Estradiol was detected in 13 of 16 effluent samples at concentrations ranging from 0.15 to 4.5 ng/L, mean 1.0 ng/L(4). Estradiol concentrations ranged from 2-5 ng/L, with one outlier at 18 ng/L, in effluents from 12 waste water treatment facilities across southern Victoria, Australia, sampled in 2004(5). Estradiol was tested for but not detected (detection limit = 2-100 ng/L) in effluent samples from sewage treatment plants in the vicinity of Barcelona, Spain, sampled from April to June, 1999(6). Estradiol was detected in 13 of 38 German municipal sewage treatment plant effluents from below the limit of quantification to a maximum of 0.003 ug/L(7).17alpha-Estradiol was detected in a typical dairy waste disposal system for 2000 dairy cows in San Jacinto, CA (ug/kg dry weight): fresh manure less than 2 hrs old, 1416piled manure at 2 weeks, 172three lagoon days at 3 months43, 54, and 8, respectively. Concentrations reported for 17beta-estradiol were 153 in fresh manure, 37 in piled manure, 18 ug/kg dry weight in dam 1, below the detection limit in dam 2, and not detected in dam 3(1). A concentration of 3 ng/L was estimated as present in runoff from agricultural fields in the Calleguas Creek watershed, Ventura County, CA which have been irrigated with treated wastewaterconcentration in applied wastewater ranged from 0.1-64 ng/L(2).As a result of analysis of effluents of several different types of municipal waste treatment plants in central Michigan, it has been concluded that human hormones (17beta-estradiol) and synthetic hormones (ethinylestradiol), not industrial chemicals with estrogenic activity, in the effluents caused male fish to produce vitellogenin, an accepted indicator of endocrine disruption(1). |
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| Soil Adsorption/Mobility | Using a Drummer soil from Indiana (pH 7.1, 2.91% organic carbon, 21% clay, 13% sand, 66% silt), a log Koc of 3.45 (Freundlich constant Kd 83.2) was measured(1), corresponding to a Koc of 3,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that estradiol is expected to be immobile in soil. Kd values of 476 have been reported for estradiol in activated sludge wastewater treatment systemsit was estimated that as much as 66% of estradiol is absorbed to sludge and 0.24% sorbed to suspended particles during waste water treatment(3). Estradiol sorption was shown to increase with the amount of incorporated organic waste. In soils with an extensive history of organic waste treatments, soil organic carbon content is the controlling factor for estrogen sorption(4).Organic waste effects on the adsorption of 17beta-estradiol in agricultural soils(1). [Table#4653] |
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| Natural Pollution Sources | Estradiol is a natural steroidal estrogen hormone released by mammals(1). 17beta-Estradiol is the natural female steroid hormone with the greatest estrogenic activity(2). |
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