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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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- July 1989 to December 1989
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- 1981
- GLP compliance:
- yes
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- A valid Buehler test conducted comparable to guideline with acceptable restrictions is available, which is reliable with restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, only a minor indication for skin sensitisation was observed in this study, presumably rather based on the adhesive used in the patch and not due to the test substance, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.
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
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- not specified
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, MA
- Diet (e.g. ad libitum): Ad libitum, Ralston Purina Guinea Pig Chow, Ralston Purina, St. Louis, MO
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Several days
- Indication of any skin lesions: No
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- intradermal
- Vehicle:
- water
- Remarks:
- Freund’s Adjuvant (1:1 commercial adjuvant with water) in an area over which the test article was immediately applied
- Concentration / amount:
- Freund’s Adjuvant (1:1 commercial adjuvant with water) in an area over which the test article was immediately applied
- Day(s)/duration:
- two injections with 0.1 mL of solution prior to topical application
- Route:
- epicutaneous, occlusive
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 5 cm² patch containing approx. 1.5 mg/patch
- Day(s)/duration:
- three application per week (Monday, Wednesday, and Friday)/ eight topical applications in total
Challenge
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- unchanged (no vehicle)
- Remarks:
- Estradiol TDD patch
- Concentration / amount:
- approx. 1.5 mg/patch
- Day(s)/duration:
- applied 14 days after last induction and with a duration of 24 h.
- No. of animals per dose:
- 10
- Details on study design:
- RANGE FINDING TESTS: Due to the nature of the test article (an adhesive patch) and the
positive response of two animals during the challenge phase of the sensitization study, a guinea pig primary skin irritation study (5 animals) was conducted. The minimal irritation noted during the primary skin study suggests the erythema and edema noted during the challenge phase may have been due to irritation.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 8
- Exposure period: every second day
- Test groups: 1
- Control group: 1
- Site: dorsal shoulder girdle
- Frequency of applications: every second day (Monday, Wednesday, and Friday)
- Duration: 6h each
- Concentrations: approx. 1.5 mg/patch
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after last induction
- Exposure period: 24h
- Test groups: 1
- Control group: 1
- Site: dorsal shoulder girdle
- Concentrations: 1.5 mg/patch
- Evaluation (hr after challenge): 24 and 48 h
Shortly before the initial topical application two intradermal injections with Freund´s adjuvant were conducted in the same area at which the patches were placed. - Positive control substance(s):
- yes
- Remarks:
- 2,4-Dinitrochlorobenzene (DNCB)
Results and discussion
- Positive control results:
- Sensitization: 100%
In vivo (non-LLNA)
Resultsopen allclose all
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Remarks on result:
- other: the performance of a negative control was not reported
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Remarks on result:
- other: the performance of a negative control was not reported
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 0.05% DNCB
- No. with + reactions:
- 10
- Total no. in group:
- 10
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 1.5 mg/patch
- No. with + reactions:
- 1
- Total no. in group:
- 10
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 0.05% DNCB
- No. with + reactions:
- 10
- Total no. in group:
- 10
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 1.5 mg/patch
- No. with + reactions:
- 2
- Total no. in group:
- 10
Any other information on results incl. tables
Primary Skin Irritation test
| Irritation scores for abraded skin sites after removal | |||
| One hour | Day 2 | ||
Animal Number | Erythema | Edema | Erythema | Edema |
9G2929 | 1E | 0 | 0 | 0 |
9G2934 | 0 | 0 | 0 | 0 |
9G2960 | 0 | 0 | 0 | 0 |
9G2965 | 1E | 0 | 0 | 0 |
9G2930 | 0 | 0 | 0 | 0 |
Mean | 0.4 | 0.0 | 0.0 | 0.0 |
Subtotal |
| 0.4 |
| |
Key | E= Epithelial Stripping |
|
|
|
Results Test item
| One day | Two days | ||
Animal Number | Erythema | Edema | Erythema | Edema |
9G2907 | 0 | 0 | 0 | 0 |
9G2912 | 0 | 0 | 0 | 0 |
9G2917 | 0 | 0 | 0 | 0 |
9G2922 | 1E | 0 | 0 | 0 |
9G2908 | 1 | 0 | 1 | 0 |
9G2913 | 0 | 0 | 0 | 0 |
9G2918 | 0 | 0 | 0 | 0 |
9G2923 | 0 | 0 | 0 | 0 |
9G2909 | 0 | 0 | 0 | 0 |
9G2914 | 0 | 0 | 0 | 0 |
Results Positive Control
| One day | Two days | ||
Animal Number | Erythema | Edema | Erythema | Edema |
9G2957 | 1 | 0 | 1 | 0 |
9G2962 | 1 | 0 | 0 | 0 |
9G2927 | 1 | 0 | 2 | 0 |
9G2932 | 1 | 1 | 1 | 0 |
9G2958 | 1 | 0 | 2 | 0 |
9G2963 | 2 | 0 | 2 | 1 |
9G2928 | 1 | 1 | 1 | 1 |
9G2933 | 1 | 0 | 1 | 0 |
9G2959 | 1 | 0 | 2 | 0 |
9G2964 | 2 | 0 | 2 | 0 |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In the present test conducted similar to OECD 406 (1981); Bühler method, 10 Dunkin-Hartley guinea pigs were dermally exposed to Estradiol via TDD Patches containing approximately 1.5 mg Estradiol as indicated in the local tolerance test. The animals were exposed eight times every second day, prior to the initial application an intradermal application of Freund´s adjuvant was performed. Fourteen days after the last topical application the animals were again dermally exposed to the patches for 24h and the reactions were documented after 24h and 48h. Only slight Erythema nor Edema occurred after induction or challenge with the Estradiol TDD patches. Erythema was scored with 1 in two animals, in one animal the irritation was found to be due to the used adhesive of the patches causing epithelial stripping. In the second animal Erythema lasted until the second reading. According to CLP, EU GHS (Regulation (EC) No 1272/2008), a response of at least 30% of the test animals of an adjuvant type guinea pig test method for skin sensitisation is considered as positive. thus the substance does not meet the classification criteria for skin sensitization according to Regulation (EU) No. 1272/2008 (CLP) or the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).
- Executive summary:
In a dermal sensitisation study comparable to OECD guideline 406 (1981) with Estradiol TDD patches 10 young adult Hartley guinea pigs were tested using the method of Buehler.
Test concentrations were selected based on the results of an irritation screening study: the concentrations used in the pretest (approximately 1.5 mg/patch of the test substance) produced only a minor irritation in one animal. Thus, in the main study 1.5 mg of the test substance contained in the TDD patch were used for epicutaneous induction and challenge. Simultaneously to the initial topical induction an intradermal injection with Freund´s adjuvant was performed.
After challenge only minor visible changes of the treated skin sites were observed in the test group animals 24 and 48 h after patch removal (= grade 0.4).
The positive control DNCB produced a sensitisation rate of 100%.
The test material produced a response in 20% of animals. According to CLP, EU GHS (Regulation (EC) No 1272/2008), a response of at least 30% of the test animals of an adjuvant type guinea pig test method for skin sensitisation is considered as positive.
Estradiol is not a dermal sensitiser in this study.
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