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EC number: 200-023-8 | CAS number: 50-28-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 975
- Report date:
- 1975
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- - Principle of test: subcutaneous injection of test item in oily solution from day 6 to 15 of gestation in female rats, the control group was treated similar only with castor oil and benzylbezoate (4:6). After cesarean section on day 19 the dams and fetuses were investigated for teratogenic and embryolethal effects. The experiments were conducted according to FDA recommendations of January 1966.
- Short description of test conditions: Male and female SPF albino rats of a Sprague Dawley strain were mated in a ratio of 1: 4 in collection cages overnight. 82 inseminated female animals were selected by daily control of the vaginal smear and placed individually in Makrolon cages "Type II" without perforated bottom. 20 or 22 animals were randomly assigned to the individual test groups. The time at which sperm appeared or a vaginal plug was found was determined to be gestation day 0. The substance was applied sc under the shaved dorsal skin as an oily solution in doses of 0.0001, 0.0003 or 0.001 mg per kg kgw per 20 animals from day 6 to 15 of gestation. 22 control animals received during the same period of pregnancy and in the same volume ratios castor oil and benzyl benzoate (4: 6) After the dams were anesthetized with chloroform (DAB 7), all fetuses were removed by caesarean section on the 19th day of pregnancy.
- Parameters analysed / observed:
Examinations of the dams
Body weight measurements on days 0, 6, 15 and 19. p. c. – determination of the number of corpuscles, determination of the number of Implantations Determination of the number of living and dead fetuses and their position in the uterus, determination of the number of resorptions with and without fetal remains and their position in the uterus, examinations for special pathological-anatomical Changes.
Examinations of the fetuses
Determination of body weight "sex determination" macroscopic and / or stereomicroscopic inspection. About 1/3 of the litters were examined for visceral malformations using the Wilson technique. About 2/3 of the litters were examined for skeletal malformations after staining with Alizarin Red S. - GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Estradiol
- EC Number:
- 200-023-8
- EC Name:
- Estradiol
- Cas Number:
- 50-28-2
- Molecular formula:
- C18H24O2
- IUPAC Name:
- estra-1,3,5(10)-triene-3,17-diol
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: W. Gassner Sulzfeld
- Weight at study initiation: females: 160-255 g and males: 315-435 g
- Housing: kept in collection cages under conventional conditions and separated by sex during acclimation period. After mating females were kept individually in Macrolon cages, type II without perforation.
- Diet (e.g. ad libitum): standard chow (Ssniff) ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- subcutaneous
- Vehicle:
- castor oil
- Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - M/F ratio per cage: 1/4 ratio
- Proof of pregnancy: vaginal plug and sperm referred to as day 0 of pregnancy - Duration of treatment / exposure:
- 20 days
- Frequency of treatment:
- daily from day 6 to day 15 post coitum
- Duration of test:
- ca. 3 weeks
- No. of animals per sex per dose:
- 20 females/group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Based on the reports of the preliminary tests No. 1053 (1973-08-10) and No. 1125 (1973-11-13)
Examinations
- Maternal examinations:
- BODY WEIGHT: Yes
- Time schedule for examinations: Day 0, 6, 15 and 19
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 19
OTHER: determination of the number of corpuscles, determination of the number of Implantations Determination of the number of living and dead fetuses and their position in the uterus, determination of the number of resorptions with and without fetal remains and their position in the uterus, examinations for special pathological-anatomical changes.
Examinations of the fetuses
Determination of body weight "sex determination" macroscopic and / or stereomicroscopic inspection. About 1/3 of the litters were examined for visceral malformations using the Wilson technique. About 2/3 of the litters were examined for skeletal malformations after staining with Alizarin Red S. - Fetal examinations:
- - External examinations: Yes: all per litter
- Skeletal examinations: Yes: all per litter
- Head examinations: No
- Anogenital distance of all live rodent pups: yes
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Endocrine findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- not examined
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not examined
- Changes in number of pregnant:
- not examined
Effect levels (maternal animals)
open allclose all
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- > 0.001 mg/kg bw/day (nominal)
- Basis for effect level:
- other: maternal toxicity
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- > 0.001 mg/kg bw/day (nominal)
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Anogenital distance of all rodent fetuses:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In 15 (13.9%) of the control fetuses examined for skeletal malformations skeletal variations were observed. The type and frequency of these variations are known from control groups of earlier experiments of the same type. Skeletal variations were also found in the fetuses of the treated dams examined for skeletal malformations after application of 0.0001 mg / kg bw in 5 fetuses (4.2%) after application of 0.0003 mg / kg bw in 21 fetuses (18.4%) and after application of 0.001 mg / kg bw in 6 fetuses (4.3%). These observed variations are considered incidental findings since the variations in the same manner and frequency are known from control groups of earlier experiments of the same type.
- Visceral malformations:
- not examined
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- > 0.001 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other:
Fetal abnormalities
- Key result
- Abnormalities:
- effects observed, non-treatment-related
- Localisation:
- other: not further specified
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
- Treatment related:
- no
Applicant's summary and conclusion
- Conclusions:
- No teratogenicity and maternal toxicity up to the highest dose level observed. No classification required.
- Executive summary:
In a study conducted to examine the developmental toxicity/teratogenicity of Estradiol, the test item was administered s.c. to 20 female Sprague Dawley rats each dose, at dose levels of 0, 0.0001, 0.0003, and 0.001 mg/kg bw/day from days 6 through 15 of gestation.
There were no adverse effects observed in the dams. No Mortality occurred, no clinical signs of toxicity were detected, no abnormal body weight changes were reported. The maternal NOEL is > 0.001mg/kg bw/day..
In 15 (13.9%) of the control fetuses skeletal variations were observed. The type and frequency of these variations are known from control groups of earlier experiments of the same type. Skeletal variations were also found in the fetuses of the treated dams after application of 0.0001 mg / kg bw in 5 fetuses (4.2%) after application of 0.0003 mg / kg bw in 21 fetuses (18.4%) and after application of 0.001 mg / kg bw in 6 fetuses (4.3%). These observed variations are considered incidental findings since the variations are known in the same manner and frequency from control groups of earlier experiments of the same type. The developmental NOEL is 0.001 mg/kg bw/day.
The present study in the rat for the detection of developmental toxicity/teratogenicity after subcutaneous application from gestation day 6 to 15 is classified acceptable and satisfies at least in parts the requirements for the detection of developmental toxicity and teratogenicity in rats.
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