Diethylstilbestrol

268.35

268.35

200-278-5

731DCA35BT

756736|3070

3077

DTXSID3020465

C433

White crystalline powder|Small plates from benzene

G - Genito urinary system and sex hormones|L - Antineoplastic and immunomodulating agents

2942000000

40.5

1.14

White to almost white Crystalline Powder

1.2

169-172 °C

407.1±25.0 °C at 760 mmHg

104°C c.c.

1.603

Practically insoluble in water;methanol: 0.1 g/mL, clear, faintly yellow

0-6°C

Vapour pressure, Pa at 20°C: 20

Relative vapour density (air = 1): 5.3

LD50 oral in rat: > 3gm/kg

vol% in air: 1.82.2

Odorless

175.64 Ų [M-H]-

CIS-ISOMER TENDS TO REVERT TO TRANS-FORM

Insoluble in water.

Hydrocarbons, Aliphatic Unsaturated

DIETHYLSTILBESTROL is incompatible with strong oxidizing agents, strong bases, acid chlorides and acid anhydrides (NTP, 1992).

III

6.1(b)

UN 3077 9/PG 3

3

45-61-36/37/38-51/53-40

53-36/37/39-45-60-61-36/37

WJ5600000

T,N

Separated from food and feedstuffs. Dry. Well closed. Keep in a well-ventilated room. Store in an area without drain or sewer access.

Isomerizes rapidly in Benzene, Chloroform, and Ether.Keep Shielded from light.

P201-P280-P305 + P351 + P338-P308 + P313

H315-H319-H335-H350-H360-H410

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U089, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.|Diethylstilbestrol is a waste chemical stream constituent which may be subjected to ultimate disposal by controlled incineration.|A good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A good candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.|The following wastewater treatment technologies have been investigated for 2,2'-diethylstilbenediol: Concentration process: Biological treatment.|For more Disposal Methods (Complete) data for DIETHYLSTILBESTROL (9 total), please visit the HSDB record page.

Drug products withdrawn or removed from the market for reasons of safety or effectiveness. Diethylstilbestrol: All oral and parenteral drug products containing 25 milligrams or more of diethylstilbestrol per unit dose.|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).

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Diethylstilbestrol (56-53-1) is listed as known to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s071diet.pdf]

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

|Danger|H315 (88.64%): Causes skin irritation [Warning Skin corrosion/irritation]|P201, P202, P261, P264, P271, P273, P280, P281, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P332+P313, P337+P313, P362, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 44 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P201, P202, P264, P273, P280, P281, P302+P352, P305+P351+P338, P308+P313, P321, P332+P313, P337+P313, P362, P391, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.|H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]|P201, P202, P260, P264, P270, P281, P308+P313, P309+P311, P314, P405, and P501

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

Excerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL 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. STORAGE PRECAUTIONS: You should protect this material from exposure to light, and store it in a refrigerator. (NTP, 1992)

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)|PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/|For more Preventive Measures (Complete) data for DIETHYLSTILBESTROL (9 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

The major hazards encountered in the use and handling of diethylstilbestrol stem from its toxicologic properties. Toxic by all routes (ie, inhalation, ingestion, dermal absorption), exposure to this white, crystalline substance may occur from its production, handling, and use as a veterinary drug. Effects from exposure may include headache, dizziness, nausea, leg cramps, and hypersensitivity reactions. More importantly, the International Agency for Research on Cancer (IARC) has designated diethylstilbestrol as a Group 1 carcinogen, meaning, "The agent is carcinogenic to humans." Mechanical ventilation which employs a high efficiency particulate arrestor (HEPA) should be used to minumize airborne levels of diethylstilbestrol. In activities and situations where over-exposure may occur, wear a protective suit and a carefully fitted respirator. Smoking, drinking, and eating should be prohibited in diethylstilbestrol work areas, and cleanliness following the handling of diethylstilbestrol should be emphasized. Diethylstilbestrol should be stored in a securely sealed, watertight container, which should be enclosed in a second, unbreakable, leakproof container. Diethylstilbestrol is a good candidate for rotary kiln or fluidized bed forms of incineration.

U089; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or manufacturing chemical intermediate.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 1 lb or 0.454 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

U089; As stipulated in 40 CFR 261.33, when diethylstilbestrol, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

Symptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females.

BILIARY EXCRETION OF METABOLITES OF ... STILBESTROL ... IN RATS WAS SHOWN ... TO BE INCR BY PRE-TREATMENT WITH HEPATIC-MICROSOMAL-ENZYME INDUCERS, & TO BE DECR BY ENZYME INHIBITORS AFTER DOSING WITH PARENT CMPD, BUT NO EFFECT WAS OBSERVED AFTER DOSING WITH METABOLITES.|Male and timed pregnant female Syrian hamsters received vitamin C (1% w/v) in drinking water for 4 days or 40 mg/kg alpha-naphthoflavone in corn oil by ip injection daily for 4 days. Male hamsters (1, 20, 85 or 240 days old) then received a single ip injection of diethylstilbestrol (DES, 20 mg/kg containing 250 uCi (3)H-DES). Pregnant hamsters received the same dose of DES ip on the 14th day of gestation. 30 min later animals were killed. Formation of diethylstilbestrol-4',4''-quinone occurred in all tissues investigated, livers and kidneys of male and female adult hamsters, neonates and fetuses, and in uterus and placenta. After injection of 75 umol/kg DES, diethylstilbestrol-4',4''-quinone was identified in liver and kidney extracts of male hamsters (12 wk old) at levels of 76 + or - 14 and 20 + or - 3 pmol/g tissue respectively. In neonates and fetuses, concn of diethylstilbestrol-4',4''-quinone after the same dose of DES were markedly less than those in adults (0.026 and 0.47% of adult levels in neonatal liver and kidney and 0.013 and 0.016% of adult levels in fetal liver and kidney respectively). Quinone metabolite levels were cut in half in response to vitamin C (44 to 60% of controls in kidneys and 41 to 65% of controls in livers). alpha-Naphthoflavone pretreatment decr renal and hepatic diethylstilbestrol-4',4''-quinone concn by 70 and 17% respectively.|Estrogens may interfere with the effects of bromocriptine; dosage adjustment may be necessary. /Estrogens/|Concurrent use with estrogens may increase calcium absorption and exacerbate nephrolithiasis in susceptible individuals; this can be used to therapeutic advantage to increase bone mass. /Estrogens/|For more Interactions (Complete) data for DIETHYLSTILBESTROL (11 total), please visit the HSDB record page.

LD50 Rat oral >3 g/kg|LD50 Rat ip 34 mg/kg|LD50 Mouse oral >3 g/kg|LD50 Mouse ip 538 mg/kg|LD50 Mouse iv 300 mg/kg

Diethylstilbestrol (DES) ... was tested in Swiss mice using the RACB protocol. This study was one of the first RACB studies conducted. DES was chosen as a known positive, based on the extensive literature ... . There were two laboratories beginning to run RACB studies, & a DES study was performed at each of these laboratories to address the issue of interlaboratory variability. From the range finding study (Task 1), levels of 1.0, 10.0 & 50.0 ppb in feed were selected for the continuous breeding phase of the study. Based on body weights & measures of food consumption, the estimated average doses were approx 0.15, 1.5, & 7.70 mgm/kg/d. In Task 2, no adverse clinical signs were noted; one high dose female died of partner-inflicted wounds. Body weight was unaffected during Task 2. The mean number of litters/pair was reduced to nearly equal to 30% of control at the high dose, while the number of live pups/litter was reduced by 77% & 64% in the medium & high dose grups, respectively. Adjusted live pup weight was unaffected. The high dose group took longer to deliver each of the first 3 litters; no fourth or fifth litters were delivered at 50 ppb. Since adverse effects were noted in Task 2, Task 3 was conducted using the using the control & high dose mice. Compared to controls, only one-third as many exposed female mice delivered a litter, & these litters contained nearly equal to 60% fewer pups. Interestingly, for the exposed-female group, adjusted pup weight was reduced by nearly equal to 20%. The only adverse effect noted in the group containing exposed males was a 10% reduction in adjusted pup body weight. The larger adverse effects were clearly seen in exposed females. After the Task 3 litters were evaluated, the F0 control & high dose mice were killed & necropsied. For females, the only effect noted was a nearly equal to 30% incr in pituitary weight. For females, 25% of controls had an unclear estrous cycle, while more than 75% of treated females did not have a clear estrous cycle. In males, a significant incr in pituitary weight (nearly equal to 15%) was also seen, along with 13-18% reductions in the weight of epididymis, cauda epididymis, & prostate. There were no demonstrable sperm effects. Task 4, the F2 generation assessment, was not conducted. This study replicated all of the salient features of the other DES study: female as the much-more-sensitive gender in the absence of significant weight effects. Differences between the results of the two studies include effects in the middle dose group, different responses in adjusted pup weight (increased at one lab, decreased at the other), & an effect on pup number in the middle dose in Task 2 (unchanged at one lab, reduced by 11% at the other). Nonetheless, in broad strokes, these studies confirmed the general replicability of the data from two different laboratories, & provided a sense of the degree of variation that might be expected across labs.|Trans-diethylstilbestrol (DES) was evaluated as a model compound in a reproductive toxicology testing scheme which has been designated "Reproductive Assessment by Continuous Breeding". In the present DES study, ... dietary levels of 1, 10 & 50 ppb DES (/about/ 99% pure) were employed in Task 2. Continuous exposure of breeding pairs /of CD-1 mice/ to dietary DES led to rapid onset of infertility in the 50 ppb DES group, whereas fertility was unaffected in the 0, 1, & 10 ppb DES groups. In addition, the 50 ppb DES pairs produced fewer litters & had fewer live pups/litter & a lower proportion of pups born alive/litter than did the pairs in the other treatment groups. Therefore a crossover mating trial was conducted to determine which sex was adversely affected (Task 3). In the crossover mating trial the proportion of detected matings did not differ significantly among treatment groups, but fertility & the number of live pups/litter & the proportion of pups born alive were significantly reduced (p<0.05),in the control male x 50 ppb DES female group versus the control male x control female group. The proportion of fertile pairs in the 50 ppb DES male x control female group did not differ significantly from either of the above two groups. Hence, exposure to 50 ppb DES in the diet primarily affected fertility in female mice. The sex of pups born alive & the live pups weights, however, did not differ significantly among the three groups. Thus, these data support the conclusion that, under the conditions of this reproductive toxicity study, DES was a reproductive toxicant in female CD-l mice as evidenced by a decreased fertility index, decreased number of litters, decreased number of live pups/litter & a lower proportion of pups born alive/litter.|... Diethylstilbestrol (CAS No. 56-53-1 ) was administered subcutaneously in corn oil to mated Swiss (CD-1) mice (12/group) on gd 9 through 16 at levels of 0, 2.5, 5, 10, 50, or 100 mg/kg/day. A trioctanoin vehicle control group and 100 mg/kg/day diethylstilbestrol in trioctanoin group (12/group) were dosed concurrently to provide comparison of data using a different vehicle. Animals were observed daily for clinical signs of toxicity on gd 9-17. Food and water weights were recorded for the animals in each group on gd 0, 3, 6, 9, 12, 16, and 17. Body weights were taken on gd 0, 3, 6, and 9-17. All animals in the developmental toxicity study were killed on gd 17 and examined for maternal body and organ weights, implant status, fetal weight, sex, and morphological development (external, visceral and skeletal). For animals dosed with DES in corn oil, no maternal lethality was observed. Pregnancy rates were 100%, 100%, 100%, 83%, 100%, and 70% for the control through high dose groups. maternal body weight gain was decreased in the 50 and 100 mg/kg/day groups compared to the corn oil controls during the gestational period (gd 0-17), and in the high dose compared to the com oil controls during the treatment period (gd 9-16). Corrected maternal body weight gain was decreased in all the DES in corn oil-treated groups compared to the corn oil control group. No dose-related clinical signs were observed. maternal relative food and water consumption for the DES in com oil groups displayed little effect of treatment. At necropsy, relative maternal liver weight was increased in the high dose group, and gravid uterine weight was decreased. The number of implantation sites per dam exhibited a decreasing trend; the number of corpora lutea per dam was decreased at greater than 10 mg/kg/day. The percent resorptions per litter was increased 3, 4, and 5-fold in the 10, 50, and 100 mg/kg/day groups, respectively. Average live litter size was decreased at the high dose, with male and female fetuses equally affected. Live fetal body weight per litter was not affected by administration of diethylstilbestrol in corn oil. The incidence of malformations per litter was increased in the high dose group, with females more severely affected than males. This was due to an increase in the incidence of extemal malformations per litter, observed as an increase in the incidence of prominent nipples in the gd 17 fetuses, a characteristic effect of prenatal diethylstilbestrol exposure. No significant increase in the incidence of visceral or skeletal malformations or variations was observed for the diethylstilbestrol in corn oil-treated litters, except at 5 mg/kg/day diethylstilbestrol in corn oil where an increase in skeletal malformations was noted. Malformations included scrambled sternebrae, perforated sternum, and fused ribs, which have not been shown to be specific to diethylstilbestrol treatment. Failure to detect a statistically significant number of skeletal malformations in the 10, 50, and 100 mg/kg/day groups may have been influenced by a reduced number of fetuses available for examination in these groups, as a result of prenatal mortality. For animals dosed with diethylstilbestrol in trioctanoin, no maternal lethality was observed. Pregnancy rates were 92% and 100% for the control and 100 mg/kg/day dose group, respectively. Maternal body weight gain was decreased in the 100 mg/kg/day diethylstilbestrol in trioctanoin group compared to the trioctanoin control during the gestational period (gd 0-17), and during the treatment period (gd 9-16). Corrected maternal body weight gain was unaffected by treatment with diethylstilbestrol in trioctanoin. No treatment-related clinical signs were observed. Maternal relative food consumption was unaffected. Maternal relative water consumption for the DES in trioctanoin was decreased during the period of gd 9-12, but not at any other time interval during treatment. At necropsy, relative maternal liver weight was unaffected, while gravid uterine weight was decreased in the 100 mg/kg/day diethylstilbestrol in trioctanoin group. The percent resorptions per litter was increased 5-fold in the 100 mg/kg/day diethylstilbestrol in trioctanoin group compared to the trioctanoin control group. Average live litter size was decreased, with male and female fetuses equally affected. Live fetal body weight per litter was decreased by administration of diethylstilbestrol in trioctanoin. The incidence of malformations per litter was not increased by diethylstilbestrol in trioctanoin treatment. However, when external, visceral, and skeletal malformations were analyzed separately, the incidence of external malformations per litter was increased, due to an increase in the incidence of prominent nipples. No significant increase in the incidence of visceral or skeletal malformations or variations was observed for the DES in trioctanoin-treated litters. In summary, maternal toxicity was evident as decreased corrected maternal body weight at greater than 2.5 mg/kg/day DES in corn oil. Thus, for DES administered subcutaneously in corn oil to Swiss mice on gd 9-16, a No Observed Adverse Effect Level (NOAEL) for maternal toxicity was not determined. Gravid uterine weight and live litter size were decreased at the high dose (100 mg/kg/day). However, the incidence of resorptions (early embryo/fetal death) was increased at greater than 10 mg/kg/day. External malformations were increased at the 100 mg/kg/day, and were characterized by an increase in the incidence of prominent nipples, observed primarily in female fetuses. There was no evidence of altered skeletal development in the fetuses of any dose group. Thus, the LOAEL for developmental toxicity was 10 mg/kg/day and the NOAEL for developmental toxicity was 5 mg/kg/day. Comparison of the effects of 100 mg/kg/day diethylstilbestrol administered in corn oil and trioctanoin indicated there was no difference in corn oil or trioctanoin as vehicles for this compound.

Diethylstilbestrol (DES) is not known to occur naturally(1).

Diethylstilbestrol's production and use in biochemical research, medicine, and also in veterinary medicine(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 570,000(SRC), determined from a structure estimation method(2), indicates that diethylstilbestrol is expected to be immobile in soil(SRC). Volatilization of diethylstilbestrol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law of 5.8X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Diethylstilbestrol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.4X10-8 mm Hg(SRC), determined from a fragment constant method(4).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 570,000(SRC), determined from an estimation method(2), indicates that diethylstilbestrol is expected to adsorb to suspended solids and sediment in water(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.8X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Hydrolysis is not expected to occur due to the lack of hydrolyzable functional groups(3). According to a classification scheme(5), an estimated BCF of 1600(SRC), from its log Kow of 5.07(8) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is very high if diethylstilbestrol is not metabolized.|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diethylstilbestrol, which has an estimated vapor pressure of 1.4X10-8 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase diethylstilbestrol may be removed from the air by wet and dry deposition(SRC).

Diethylstilbestrol is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(1).

An estimated BCF of 1600 was calculated for diethylstilbestrol(SRC), using a log Kow of 5.07(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high if diethylstilbestrol is not metabolized.

1.38e+04 L/kg|Using a structure estimation method based on molecular connectivity indices(1), the Koc for diethylstilbestrol can be estimated to be 570,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that diethylstilbestrol is expected to be immobile in soil.

The Henry's Law constant for diethylstilbestrol is estimated as 5.8X10-8 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that diethylstilbestrol is expected to be essentially nonvolatile from water surfaces(2). Diethylstilbestrol's Henry's Law constant(1) indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Diethylstilbestrol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.4X10-8 mm Hg(3), determined from a fragment constant method(SRC).

DRINKING WATER: Diethylstilbestrol was detected in German drinking water samples at a concentration of 0.11-0.26 ng/l(1,2).

In 1972 and 1973, diethylstilbestrol was detected in beef livers at the following concentration, number of samples not reported: <2 ug/kg, 2 and 0.5% pos, respectively(1); in 1972 and 1973, sheep livers, 1900 samples, residual levels, <2% pos(1); from 1973 to June 1976, beef livers, 9426 samples, greater than or equal to 0.5 ug/kg, 0.6% pos(1).

... food contaminant ... in beef ... chickens|NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,478 workers (920 of these are female) are potentially exposed to diethylstilbestrol in the US(1). Occupational exposure to diethylstilbestrol may occur through dermal contact with this compound at workplaces where diethylstilbestrol is produced or used(SRC). Air samples collected inside the plastic suits of full-time workers in a plant manufacturing diethylstilbestrol contained 0.4-1.8 ug/cu m diethylstilbestrol(2). Two sets of air samples collected in areas outside the main work room contained 0.2 ug/cu m and 12.8 ug/cu m(2). An air sample from a finishing room contained 24 ug/cu m diethylstilbestrol(2). Ambient air samples in three plants where diethylstilbestrol was mixed with animal feed contained 0.002-1.03 ug/cu m diethylstilbestrol(2).

Used in the treatment of prostate cancer. Previously used in the prevention of miscarriage or premature delivery in pregnant women prone to miscarriage or premature delivery.

...DES also have been used in the treatment of prostate cancer to reduce testicular androgen production secondary to inhibition of LH release from the pituitary.|... Two major uses are as a component of combination oral contraceptives and for hormone replacement therapy in postmenopausal women. /Estrogens/|Chemotherapeutic agents useful in neoplastic disease /of the/ breast, prostate /from table/|Antineoplastic Agents, Hormonal; Carcinogens; Contraceptives, Postcoital, Synthetic; Estrogens, Non-Steroidal|For more Therapeutic Uses (Complete) data for DIETHYLSTILBESTROL (14 total), please visit the HSDB record page.

Nausea & vomiting are an initial reaction...Fullness & tenderness of the breast & edema...Severe migraine in some...Reactivate or exacerbate endometriosis and its attendant pain. /Estrogens/|DIETHYLSTILBESTROL TAKEN DURING PREGNANCY HAS BEEN SHOWN TO BE CAUSALLY ASSOC WITH INCR IN VAGINAL AND CERVICAL CLEAR-CELL ADENOCARCINOMA IN DAUGHTERS, PRIMARILY IN THOSE BETWEEN THE AGES OF 10 AND 30 YR. THE RISK APPEARS TO BE IN THE ORDER OF 0.14-1.4/1000 EXPOSED DAUGHTERS UP TO THE AGE OF 24 YR.|VET: TOXIC EFFECTS INCLUDE THROMBOCYTOPENIA, GYNECOMASTIA, AND FLUID RETENTION.|... FIVE PATIENTS HAD SYMPTOMS OF PRESBYOPIA ASSOCIATED WITH USE OF DIETHYLSTILBESTROL & ... THESE SYMPTOMS ABATED ON DISCONTINUANCE OF DRUG.|For more Drug Warnings (Complete) data for DIETHYLSTILBESTROL (24 total), please visit the HSDB record page.

Diethylstilbestrol is a synthetic estrogen that was developed to supplement a woman's natural estrogen production. In 1971, the Food and Drug Administration (FDA) issued a Drug Bulletin advising physicians to stop prescribing DES to pregnant women because it was linked to a rare vaginal cancer in female offspring.

Non-steroidal compounds with estrogenic activity. (See all compounds classified as Estrogens, Non-Steroidal.)|Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. (See all compounds classified as Carcinogens.)

ONLY TRACES ... COULD BE FOUND IN TISSUES 24 HR AFTER ADMIN TO SHEEP & GOATS.|... SMALL AMT EXCRETED UNCHANGED. STILBESTROL LABELLED WITH (14)C IN TWO METHYLENE GROUPS, INJECTED IN SMALL DOSES INTO RATS, IS MOSTLY EXCRETED IN BILE ... ONLY 5% OF DOSE IS EXCRETED IN URINE. NO (14)CO2 IS EXCRETED IN EXPIRED AIR, SO PRESUMABLY MOLECULE IS STABLE.|DES is readily absorbed from the GI tract following oral administration. The drug is slowly inactivated in the liver and excreted in urine and feces, principally as the glucuronide.

Hepatic.|IN SMALL DOSES, ABOUT 70% IS CONJUGATED WITH GLUCURONIC ACID AT ONE OF TWO HYDROXYL GROUPS, VERY LITTLE SULFATE CONJUGATION OCCURS, & ONLY SMALL AMT ARE EXCRETED UNCHANGED.|MAJOR METABOLITES OF DES IN SEVERAL SPECIES (RAT, MOUSE, HAMSTER, PRIMATES) ARE DIENOESTROL AND OMEGA-HYDROXYDIENOESTROL ... .|OXIDATIVE METABOLISM OF DES WAS MEASURED IN MALE & FEMALE GENITAL TRACTS OF FETAL MOUSE IN ORGAN CULTURE. MAJOR OXIDATIVE METABOLITE WAS Z,Z-DIENESTROL, WHOSE FORMATION APPEARED TO BE TIME DEPENDENT IN ISOLATED FETAL GENITAL TRACT OF BOTH SEXES. IN ADDN, FETAL GENITAL TRACTS WERE CAPABLE OF O-METHYLATION OF DES. A NEW METABOLITE, 4'-O-METHYL-DES, WAS FORMED IN FETAL GENITAL TISSUES BUT NOT IN LIVER CULTURES. CONJUGATION OF DES OCCURRED EXTENSIVELY IN FETAL LIVER & PLACENTA BUT NOT IN FETAL GENITAL TISSUES.|Microsomes were prepared from livers of untreated male hamsters (8 wk old) by differential centrifugation. Microsome-mediated reactions were carried out using 10 to 250 uM diethylstilbestrol (DES) with (0.5 to 2.0 mM) cumene hydroperoxide or 100 uM DES with 1 to 5 mM nicotinamide adenine dinucleotide phosphate. Diethylstilbestrol-4',4''-quinone formation by fetal liver homogenate was carried out by incubating 100 uM DES, 1.5 mM cumene hydroperoxide and fetal homogenate (4 mg/ml protein) for 10 min. In vitro, the time dependent formation of diethylstilbestrol-4',4''-quinone as a function of microsomal protein, cofactor or substrate concn was demonstrated. Quinone formation was time dependent and increased in linear fashion for up to 10 min, then remained at a plateau level when incubation times were further increased. Diethylstilbestrol-4',4''-quinone was also formed by fetal liver homogenate. The microsome mediated oxidation of DES to quinone was inhibited 93% by 500 uM 2(3-t-butyl-4-hydroxyanisole), 96% by 500 uM N,N,N',N'-tetramethyl-p-phenylenediamine, 83% by 500 uM n-octylamine, 97% by 500 uM potassium cyanide, and 6% by 1 mM cyclohexene oxide. In microsomal incubations with nicotinamide-adenine dinucleotide phosphate, quinone formation was below detection limits (< 0.005 nmol/mg protein/min).|For more Metabolism/Metabolites (Complete) data for DIETHYLSTILBESTROL (7 total), please visit the HSDB record page.

Estrogens diffuse into their target cells and interact with a protein receptor, the estrogen receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. The effect of Estrogen binding their receptors causes downstream increases 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).|The precise mechanism(s) of action of DES as a postcoital contraceptive is not fully understood; however, the drug appears to inhibit nidation (implantation) of the fertilized ovum in the endometrium when administered within 72 hours following coitus. The postcoital contraceptive activity of the drug may involve effects mediated via decreased concentrations of circulating progesterone, effects on tubal motility resulting in accelerated passage of the ovum into the uterus, and inhibition of synthesis of carbonic anhydrase in the endometrium.|... DES ... inhibited the postcastration rise in plasma FSH amd LH levels ... . In addition, DES stimulated large increases in prolactin secretion ...

SYMPTOMS: Symptoms of exposure to this compound via ingestion include dysmenorrhea, premenstrual-like syndrome, amenorrhea (during and after), increase in size of uterine fibromyomata, vaginal candidiasis, change in cervical eversion and of cervical secretion, cystitis-like syndrome; tenderness, enlargement and secretion of the breasts; abdominal cramps, bloating, cholestatic jaundice, chloasma or melasma, erythema multiforme, erythema nodosum, loss of scalp hair hemorrhagic eruptions, hirsutism, steepening of corneal curvature, intolerance to contact lenses, headache, migraine, dizziness, mental depression, chorea, decrease or increase in weight, reduced carbohydrate tolerance, aggravation of porphyria, edema and changes in libido. Gynaecomastia is the main side effect in the male. Exposure may also cause proliferation and withdrawal bleeding, sodium retention, nitrogen retention, alterations in liver function, jaundice, nausea and vomiting. It can cause male impotence and transsexual changes. It may also cause congenital malformation in the fetus. Human reproductive effects by ingestion include abnormal spermatogenesis, changes in the testes, epididymis and sperm duct; menstrual cycle changes or disorders, changes in female fertility, developmental abnormalities of the fetal urogenital system, germ cell effects in offspring and delayed effects in the newborn. ACUTE/CHRONIC HAZARDS: This chemical may be harmful if swallowed or inhaled. It may cause irritation of the skin, eyes, mucous membranes and upper respiratory tract. When heated to decomposition it emits toxic fumes of carbon monoxide and carbon dioxide. (NTP, 1992)|Carcinogens, Mutagens, Teratogens

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. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. 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. OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

... VAGINAL ADENOSIS IN 13/34 FEMALE PATIENTS EXPOSED IN UTERO TO DES, & IN 7 THERE WERE TRANSVERSE CERVICAL OR VAGINAL RIDGES. SIMILAR LESIONS ... NOT PRESENT IN 275 GIRLS OF ... NO HISTORY OF DES EXPOSURE IN UTERO.|AMONG 24 FEMALE PATIENTS WITH GONADAL DYSGENESIS ... TREATED FOR 5 OR MORE YR WITH DES, ENDOMETRIAL CARCINOMA DEVELOPED IN 2 ... THREE OTHER CASES ... PREVIOUSLY ... REPORTED ... OF THE TOTAL OF 5 ... 3 WERE OF UNUSUAL MIXED OR ADENOSQUAMOUS TYPE.|... PRIMARY CARCINOMA OF BREAST WITH PAGET'S DISEASE OF NIPPLE IN MAN WHO HAD RECEIVED LONG-TERM TREATMENT WITH DES FOR CARCINOMA OF PROSTATE.|STRUCTURAL CHANGES ... WERE REPORTED ... IN THE UTERUS AND FALLOPIAN TUBE OF 40 TO 60 FEMALES EXPOSED PRENATALLY TO DES. SMALL ENDOMETRIAL CAVITIES, 'T'-SHAPED UTERI AND DILATED CORNUAL AREAS WERE NOTED. THEY FOUND NO SIMILAR CHANGES IN ... UNEXPOSED FEMALES OF THE SAME AGE.|For more Human Toxicity Excerpts (Complete) data for DIETHYLSTILBESTROL (14 total), please visit the HSDB record page.

Agostilben

Grade: USP

Phenol, 4,4'-[(1E)-1,2-diethyl-1,2-ethenediyl]bis-: ACTIVE|S - indicates a substance that is identified in a final Significant New Use Rule.|Non-steroid, synthetic estrogen, always in trans form. It is most active of commonly used stilbene cmpd.

AOAC Method 956.10. Diethylstilbestrol in feeds. Spectrophotometric method.|AOAC Method 960.61. Diethylstilbestrol in drugs. Spectrophotometric method.|Thin layer chromatography is used for determination of diethylstilbestrol in feeds. Sensitivity of this method is 0.07 mg/kg.|Ultra-violet spectrometry at a wavelength of 418 nm can be used for determination of diethylstilbestrol in drugs and vegetable oils.

FLUORIMETRIC METHOD USED TO DETECT DIETHYLSTILBESTROL AT 1 PPB IN ANIMAL TISSUES & URINE.|DES AT PICOGRAM LEVEL IN BOVINE URINE WAS IDENTIFIED BY CAPILLARY GAS CHROMATOGRAPHY WITH NEGATIVE CHEMICAL IONIZATION MASS SPECTROMETRY USING METHANE OR METHANE-NITROUS OXIDE (4:1) AS REAGENT GAS.|MODIFIED ELECTRON CAPTURE GAS-LIQ CHROMATOGRAPHIC METHOD USED FOR DETECTION OF DES IN CATTLE URINE.|Column chromotography/flame ionization detection is used for determination of diethylstilbestrol in biological fluids and animal tissues. Sensitivity of this method is 8 ug/l ml sample.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Veterinary Drug -> GROWTH_PROMOTER; -> JECFA Functional Classes|Health Hazards -> Carcinogens, Mutagens, Teratogens|Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Veterinary Drug -> GROWTH_PROMOTER;