Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 200-164-5 | CAS number: 53-16-7
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
A registration of estrone was already submitted earlier and is public available on the ECHA website. Chapter 7, which is still valid from today's perspective, was amended to fulfill the current information requirements. Consequently the migrated data (IUCLID 5 to IUCLID 6) was kept unchanged and only modified if there was a need for further information and/or to pass the technical completeness check (TCC).
Estradiol and its metabolite estrone are essential endogeneous hormones. Estradiol-17ß is the most active naturally occuring estrogenic hormone. Estradiol and estrone are widely used for oral contraception and in post-menopausal hormonal therapy. Estradiol and estrone are generally negative in the ICH ( International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) core battery of tests according to the the literature review published by Joosten (Toxicology Letters 151, 113 -134) in 2004. A different picture with more positive tests appears when other endpoints and less commonly used cell types are used. Several examples of estrogens with conflicting results (positive, negative, variable results) are described.
Estrone and its surrogat estrone methylether are not mutagenic in gene mutation assays (bacteria and mammalian cells). Estrone can cause chromosomal aberrations.
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- CHO cells used in the current investigation were routinely grown in 75cm² Corning plastic flasks in 10 ml of McCoy’s 5a medium supplemented with 10% fetal calf serum and antibiotics consisting of penicillin-G, (100 U/ml) and streptomycin, (100 µg/ml). The cultures were incubated in an atmosphere of 5% CO2 in air. To test the effect of steroid hormones, cultures were set up 24 h prior to the treatment by seeding approx. 1.6 x 10 to 6 cells per flask. Treatments were given by exposing the cultures to test compounds dissolved in DMSO and suspended in the culture medium for 12 h. The control cultures contained 0.5% of DMSO and were incubated under identical conditions. The procedure for the preparation of chromosomes to score for the abnormalities
is described in Experientia, 38 (1982) 845-846. - GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
- Specific details on test material used for the study:
- The test material was procured from Sigma, St. Louis, MO.
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- The CHO cells were obtained from Environmental Health Research and Testing, Lexington, KY. The cells were not used at a passage level of more than 15 after cloning, and were thawed routinely from liquid nitrogen storage and maintained by transferring twice a week.
- Metabolic activation:
- not specified
- Test concentrations with justification for top dose:
- 10 to minus five M; 5 x 10 to minus five M; 10 to minus 4 M
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- no
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- not applicable
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- not examined
- Conclusions:
- positive
- Executive summary:
The effect of steroid hormones on the chromosomes of cultured Chinese hamster ovary (CHO) cells was studied. It was noticed that estradiol-17fl, estrone, estriol and ethynyl estradiol were effective in producing various types of chromosome aberrations. The percentage of these abnormalities increased with increasing concentrations of steroids used.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Primary liver-cell-mediated mutagenesis assays were performed according to the method previously described by Langenbach et al. (Proc. Natl. Acad. Sci. 75, 2864-2867 (1978)). V79 Chinese hamster cells were plated in 25cm² flasks at a concentration of 3.0 X 1000000 in minimal essential medium (MEM) containing 10% fetal calf serum (FCS). After 24 h, the medium was removed, and freshly isolated liver cells were seeded at a concentration of 2x 10000000 viable cells/flask on top of the V79 Chinese hamster cells. Cells were left to stand in Williams’ E medium with 10% FCS at 37°C for 3 h to allow for attachment this medium was then replaced with medium containing the chemicals to be tested, After 48 h, the cells were washed twice with Earle’s BSS, Ca, Mg -free, and incubated for 2 additional h in MEM + 10% FCS. The V79 cells were then trypsinized and replated for the determination of the cytotoxicity and resistance to ouabain and 8 -azaguanine.
In one experiment, - GLP compliance:
- not specified
- Type of assay:
- mammalian cell gene mutation assay
- Specific details on test material used for the study:
- The test material was purchased from Sigma Chemical Co (St. Louis, MO, USA)
- Target gene:
- resistance to ouabain and 8-azaguanine
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- originally obtained from dr. E. Hubermann (Oak Ridge National Laboratory, Oak Ridge, TN, USA)
- Metabolic activation:
- with and without
- Metabolic activation system:
- freshly isolated liver cells obtained from 6-8 week old male or female BDIV rats; in one experiment rats were given an i.p. injection of Aroclor 1254 (500 mg/kg) in olive oil 5 days before perfusion.
- Test concentrations with justification for top dose:
- 0, 50, 75, 100 µM (in the absence or presence of liver cells)
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- N-dimethylnitrosamine
- Details on test system and experimental conditions:
- The V79 cells were plated at a concentration of 2 X 100000 cells/60-mm dish for the determination of resistance to 8-azaguanine (AZA’) and I000000 cells/60-mm dish for resistance to ouabain (GUA’). After 72 h of expression time, the drugs, 8-azaguanine and ouabain, were added to give final concentrations of 20 µg/ml and 1 mM, respectively. The medium was changed 3 days later and replaced with Eagle’s MEM containing non-essential amino acids, dialyzed FCS and 8-azaguanine; for ouabain, the medium containing non-dialyzed FCS and the selective drug was changed 4 days later. The cultures were fixed and the colonies stained with Giemsa at 10 days for AZA’ and at 12 days for OWA’ mutants. The mutation frequency (resulting from the mean of
colonies observed in the 8 dishes) was calculated per 1000000 survivors. - Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- negative
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- TREATMENT OF TEST MATERIAL PRIOR TO TESTING
On the day of the experiment, the test article was dissolved in the vehicle. The test article formed a suspension in the stem solution. - Target gene:
- Histidine locus
- Species / strain / cell type:
- other: TA 1535, TA 1537, TA 98, TA 102 and TA 100
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver S9 microsomal fraction
- Test concentrations with justification for top dose:
- up to 5.0 mg/plate
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: - S9 Mix: Sodium azide: TA100, TA 1535; 4-NOPD: TA 1537, TA 98; MMS: TA 102; + S9 Mix: 2-AA all strains
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 98, TA 102 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
Estrone methyether did not show a mutagenic potential in the bacterial reverse mutation assay. - Executive summary:
- Estrone methyether did not show a mutagenic potential in a bacterial reverse mutation assay (Ames test in S. typhimurium strains TA98, TA100, TA102, TA1535, TA1537) when tested up to the highest recommended dose level of 5.0 mg/plate in the absense or presense of extrinsic metabolic activation (liver S9 mix form Aroclor 1254 -treated rats).
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- No genotoxicity studies were conducted with estrone; read across approach with results of a study with estron-methylether (ZK 5512).Estrone methylether is a steroidal hormone with a weak estrogenic activity. Pharmacological studies have yielded results which show that, despite the weak binding to the estrogen receptor in vitro, a full estrogenic effect can be expected following subcutaneous administration of 1 mg/kg estrone methylether in vivo in rats. It thus can be assumed that the 3-methylether of the estrone in the mammalien organism is transformed into the estrogenically active natural hormone estrone. Therefore, it is possible to use knowledge of estrone methylether for the assessment of estrone:
- Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 98, TA 102 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
Estrone methyether did not show a mutagenic potential in the bacterial reverse mutation assay. - Executive summary:
- Estrone methyether did not show a mutagenic potential in a bacterial reverse mutation assay (Ames test in S. typhimurium strains TA98, TA100, TA102, TA1535, TA1537) when tested up to the highest recommended dose level of 5.0 mg/plate in the absense or presense of extrinsic metabolic activation (liver S9 mix form Aroclor 1254 -treated rats).
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Mode of Action Analysis / Human Relevance Framework
Estrone is an endogenous sex hormone and an approved drug since several decades. The active ingredient, synthetic estrone, is similar both chemically and biologically to endogenously produced human estrone. Estrone belongs to the category “steroidal estrogens” and is one of the pharmacologically less-active metabolites of 17β-estradiol which is the most the most potent of the naturally occurring estrogens (17ß-estradiol, estrone, estriol).The toxic effects of steroidal estrogens like estradiol <-> estrone are an exaggeration of the normal pharmacological effects and result in an increase of female characteristics. Estradiol and estrone are widely used for oral contraception and in post-menopausal hormonal therapy for many years. Therefore a wide base of clinical experience is available pointing out various types of adverse effects.
Additional information
A registration of estrone was already submitted earlier and is public available on the ECHA website. Chapter 7, which is still valid from today's perspective, was amended to fulfill the current information requirements. Consequently the migrated data (IUCLID 5 to IUCLID 6) was kept unchanged and only modified if there was a need for further information and/or to pass the technical completeness check (TCC).
No genotoxicity studies were conducted with estrone (ZK 5019); read across approach with results of a study with estron-methylether (ZK 5512). Estrone methylether is a steroidal hormone with a weak estrogenic activity. Pharmacological studies have yielded results which show that, despite the weak binding to the estrogen receptor in vitro, a full estrogenic effect can be expected following subcutaneous administration of 1 mg/kg estrone methylether in vivo in rats. It can thus to be assumed that the 3-methylether of the estrone in the mammalien organism is transformed into the estrogenically active natural hormone estrone (analogous to the transformation of mestranol into ethinylestradiol). Therefore, it is possible to use knowledge of estrone methylether for the assessment of estrone:
ZK 5512 did not show a mutagenic potential in a bacterial reverse mutation assay (Ames test in S. typhimurium strains TA98, TA100, TA102, TA1535, TA1537) when tested up to the highest recommended dose level of 5.0 mg/plate in the absense or presense of extrinsic metabolic activation (liver S9 mix form Aroclor 1254 -treated rats). [Schering AG, Report No. AL92; 1996-06-05]
Additionally, positive results of genotoxicity studies with estrone are cited in RTECS database (Aug 2011):
DNA adduct were found at 870 nmol/kg after oral application of estrone to rats [Chemico-Biological Interactions. (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1969- v. 23, p. 13, 1978 (CBINA8)]
After intraperitoneal application in rats mutation was found in cytogenetic analysis at a dose of 10 mg/kg [Current Science. (Current Science Assoc., Sadashivanagar P.O., Bangalore 560 080, India) V.1- 1932- v. 50, p. 425, 1981 (CUSCAM)]
Sister chromatid exchange was reported in hamster ovary cells at 10 umol/L [Experientia. (Birkhaeuser Verlag, POB 133, CH-4010 Basel, Switzerland) V.1- 1945- v. 44, p. 62, 1988 (EXPEAM)]
In hamster lung cells a specific locus test was positive at 100 nmol/L [Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- v. 550, p. 109, 2004 (MUREAV)]
Saccharomyces cerivisiae (microorganism) mutation test was positive at 31.6 umol/L/6H [Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- v. 676, p. 113, 2009 (MUREAV)]
In hamster ovary cells cytogenetic analysis was found positive at 50 umol/L [Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977- v. 29, p. 201, 1985 (TOLED5)]
Justification for classification or non-classification
Various in vitro and in vivo test systems for investigation of genotoxic properties of estradiol and estrone have led to contradictive results. Different publications show mutagenic effects in vivo and in vitro. However, different estrogens are tested in standard genotoxicity tests and did not show any genotoxic potential. Therefore, there is no sufficient evidences available to classify the substance estrone as genotoxic.
Classification according to Regulation (EC) No. 1272/2008 (CLP) would not appear to be appropiate.
The non-classification is in accordance with German legislation for classification of estrogenic steroid hormones. The German Committee on Hazardous Substances (AGS) recommended for estrogenic steroid hormones classification as:
Toxicity to reproduction - Fertility: Category 1A
Toxicity to reproduction - Development: Category 2
Carcinogenicity: Category 2
See Technical Rule for Hazardous Substances 905; elaborated by the German Committee on Hazardous Substances (AGS) and published by the German Federal Ministry of Labour and Social Affairs, version: 19.04.2016, only available in German,URLhttp://www.baua.de/de/Themen-von-A-Z/Gefahrstoffe/TRGS/Begruendungen- 905-906.html.
The associated documentation and justification for grouping steroid hormones and their classification was published in 09/1999. Estrone is mentioned in attachment 2 on page 16.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.