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Diss Factsheets

Administrative data

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).

Skin corrosion/irritation

Estrone was investigated regarding its potential skin irritating properties using a SkinEthic reconstituted epidermis model (EPISKIN Standard Model). After 15 minutes of exposure to the neat substance and an additional incubation period of 42 hours cell viability of the tissues treated with the test substance was comparable to the cell viability of the negative control tissues. Therefore, estrone can be classified as non-irritating compound .

Eye Irritation

Estrone was investigated regarding its potential eye irritating properties using the BCOP Test. It did not induce ocular irritation through the endpoints opacity and permeability, resulting in a mean in vitro irritancy score of -0.8 after 240 minutes of treatment. Therefore, estrone can be classified as non-irritating compound.

The test item was tested in the in vitro assay applying the Hen´s Egg Test on the Chorio-Allantoic Membrane (HET-CAM) test method. This is a method that makes use of the chorioallantoic mambrane (CAM) of fertilized chicken eggs. For determination of acut effects on haemorrhage, lysis of blood vessels and coagulation the undiluted test item was directly applied onto the CAM. for 5 minutes. The Irritation Score (IS) value was calculated to be 0 for the test item which was interpreted as being non irritant. The results of the positive ( SDS 1% in physiologic saline) and negative (physiologic saline solution) controls confirmed the validity of the test system.

The reconstructed human corneal epithelial tissue-based in vitro test method (SkinEthic™ HCE) was conducted with the test item. The undiluted test item was applied topically to the reconstructed HCE tissue. After an exposure period of 60 minutes followed by a 16 hours post-treatment incubation period the cell viability was measured to be about 95% by the MTT conversion assay. Thus the test item is predicted as non-irritant under the conditions of this test method.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Dec 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: OECD Guideline 439 (In Vitro Skin Irritation)
Qualifier:
according to guideline
Guideline:
other: EU Method B.46 (In Vitro Skin Irritation)
GLP compliance:
yes (incl. QA statement)
Species:
other: three-dimensional human epidermis model (EPISKIN Standard Model of Skin Ethic Laboratories)
Vehicle:
water
Controls:
other: Negative control: phosphate buffered saline (PBS); Positive control: 5% (aq) Sodium dodecyl sulphate (SDS) in PBS
Duration of treatment / exposure:
15 minutes exposure to the substance with an following incubation period of 42 hours at 37°C
Irritation / corrosion parameter:
% tissue viability
Value:
ca. 99
Negative controls validity:
valid
Positive controls validity:
valid

Estrone did not interact with MTT.

After 15 minutes of exposure to the neat substance and an additional incubation period of 42 hours the mean tissue viability of tissues treated with the test substance was 99% (negative control tissues 100%, positive control tissues 12%).

Interpretation of results:
other: negative
Conclusions:
non-irritating
Executive summary:

Estrone was investigated regarding its potential skin irritating properties using a SkinEthic reconstituted epidermis model (EPISKIN Standard Model). After 15 minutes of exposure to the neat substance and an additional incubation period of 42 hours cell viability of the tissues treated with the test substance was comparable to the cell viability of the negative control tissues. Therefore, estrone can be classified as non-irritating compound .

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Dec 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: OECD Guideline 437 (BCOP test method)
GLP compliance:
yes (incl. QA statement)
Species:
other: bovine eyes from young cattle; used as soon as possible after slaughter on the same day
Vehicle:
unchanged (no vehicle)
Controls:
other: Negative control: physiological saline; Positive control: 20% (w/v) Imidazole solution prepared in physiological saline
Duration of treatment / exposure:
240 minutes
Irritation parameter:
in vitro irritation score
Run / experiment:
mean
Value:
-0.8
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid

The corneas treated with estrone showed opacity values ranging from -1 to 0 and permeability values ranging from 0.010 to 0.020. The corneas were clear after the 240 minutes of treatment with estrone. No pH effect of the test substance was observed on the rinsing medium. Hence, the in vitro irritancy scores ranged from -0.9 to 0.2 after 240 minutes of treatment with estrone (for the negative controls it ranged from 0.0 to 0.9 and for the positive controls it ranged from 102 to 114).

Summary of opacity, permeability and in vitro scores:

Treatment   Mean Opacity  Mean Permeability  Mean in vitro Irritation Score
 Negative control 0.000  0.0 
 Positive control 81  1.672  106.1 
 Estrone -1  0.015  -0.8 
Interpretation of results:
other: negative
Conclusions:
not-irritating
Executive summary:

Estrone was investigated regarding its potential eye irritating properties using the BCOP Test. It did not induce ocular irritation through the endpoints opacity and permeability, resulting in a mean in vitro irritancy score of -0.8 after 240 minutes of treatment. Therefore, estrone can be classified as non-irritating compound.

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
August 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Principles of method if other than guideline:
- Principle of test:
Assessment of ocular irritation potential of the test substance by determination of cytotoxic effects on a human corneal epithelium (HCE) cell model (similar to EpiOcular).
The HCE model is currently involved in the eye irritation validation conducted by COLIPA following ECVAM guidelines. Furthermore, it is routinely used by the major Cosmetic and Pharmaceutical companies, and has already been prevalidated in 2004 (van Goethem et. al., Tox in Vitro 20, 2006, 1-17). This model is recognized as the model of choice and scientifically relevant as documented by several publications (e.g. Alepee et. al., Toxicology in Vitro 34 (2016) 55–70).
GLP compliance:
yes (incl. QA statement)
Species:
other: human corneal epithelial cells
Strain:
other: not applicable
Details on test animals or tissues and environmental conditions:
The experiment was carried out on a Human Corneal Epithelial (HCE) Model, which is standardized and commercially available (SkinEthicTM Human Corneal Epithelial Model (HCE), SkinEthic, France). Inserts were of 0.5 cm² size. When cultivated at the air-liquid interface in a chemically defined medium, the immortalized human cornea epithelial cells reconstruct a corneal epithelial tissue (mucosa), without a stratum corneum, ultra-structurally (tissue morphology and thickness) similar to the corneal mucosa of the human eye.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
30 mg per insert, plus 30 µl PBS to moisten and ensure good contact to the tissue
Duration of treatment / exposure:
60 min at room temperature
Duration of post- treatment incubation (in vitro):
16 hours in the incubator (37°C, 5% CO2, maximum humidity)
Number of animals or in vitro replicates:
three
Details on study design:
The irritation potential of the test item is assessed by determination of its cytotoxic effect on an reconstructed human ocular epithelium. The test principle is based on the MTT assay reflecting the cell viability after exposure of the cornea equivalent to topically applied test item. The test item is applied pure. Since the test item is a solution (ca. 40% in ethyl acetate) the solvent is tested in parallel to distinguish potential toxic effects of the test item from the effects of the solvent. After the post-exposure incubation of 16 hours in the incubator (37 +/- 2 °C, 5 % CO2, maximum humidity) MTT reduction is performed. Cell viability is measured by the amount of MTT reduction, i.e. an OD value following exposure to the negative or positive control substances or the test item. A test substance is predicted to be an ocular irritant if the mean relative tissue viability (%) exposed to the test substance is ≤ 50 %.
Irritation parameter:
other: cell viability (%)
Value:
ca. 98
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid

Table 1: Tabular Summary of the results

 

 Sample No.  Test item  OD mean*  StdDev  % Viability
 1 -3  Negative control PBS  0.80  0.03  100.00
 4 -6  Positive control SDS 0.3%  0.09  0.08  11.34
 7 -9  Estrone  0.79  0.03  98.37

*6 values

Interpretation of results:
other: negative
Executive summary:

The reconstructed human corneal epithelial tissue-based in vitro test method (SkinEthic™ HCE) was conducted with the test item. The undiluted test item was applied topically to the reconstructed HCE tissue. After an exposure period of 60 minutes followed by a 16 hours post-treatment incubation period the cell viability was measured to be about 95% by the MTT conversion assay. Thus the test item is predicted as non-irritant under the conditions of this test method.

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
according to guideline
Guideline:
other: Appendix B3 of "ICCVAM Test Method Evaluation Report: Current Validation Status of In Vitro Test Methods Proposed for Identifying Eye Injury Hazard Potential of Chemicals and Products", NIH Publication No. 10-7553, September 2010.
Principles of method if other than guideline:
- Principle of test: The Hen´s Egg Test on the Chorio-Allantoic Membrane (HET-CAM) is a test method which implies the use of a complete tissue constituted of blood vessels and proteins that is capable of responding to chemical injury with an inflammatory process similar to the one occuring in the conjunctival tissue of the eye.

- Short description of test conditions: The test substance is applied directly to the chorioallantoic membrane (CAM) of fertilized chicken eggs

- Parameters analysed / observed: acute effects on haemorrhage, lysis of blood vessels and coagulation
GLP compliance:
yes (incl. QA statement)
Details on test animals or tissues and environmental conditions:
SOURCE OF FERTILIZED CHICKEN EGGS
- Source: Brinkschulte Josef GmbH & Co.KG, 48308 Senden
- Number of eggs: 4
- Characteristics of donor animals fertile Lohmann Brown hens
- Treatment conditions of eggs prior initiating testing: day 1-7: an incubator with an automatic rotating device (e.g. Ehret GmbH), optimum temperature : 37.5 °C, relative humidity 63%. day 8: with the large end
upward and not rotated for ensuring accessibility to the Chorioallantoic membrane (CAM) region
- Time interval prior to initiating testing: 8 days
- indication of any existing defects or lesions in eggs: After 7 days of incubation, all eggs were candled in order to discard those that were defect and to mark the air bubble.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 300 μl/egg which corresponded to an amount from an average of 190 mg


Duration of treatment / exposure:
300 sec
Duration of post- treatment incubation (in vitro):
not applicable
Number of animals or in vitro replicates:
4 eggs
Details on study design:
At day 8 of incubation the sections marked for the air bubble were sawed out of the shell. The inner membrane was moistened with NaCl 0.9 % and carefully removed with forceps. Only eggs with normally developed embryos and blood vessel systems were used for testing. Undilutet test item was applied directly onto the Chorioallantoic membrane (CAM) of each egg in a volume of 300 µL undiluted test item. 4 eggs each were used for the test item, negative and positive controls.

Observations of effects to the blood vessels, albumen or embryo over a period of 300 seconds after substance application are determined for each single egg. The time to the appearance of each of the observations mentioned above has been monitored and recorded. If no effect appeared during the observation period of 300 seconds (observation = 0) the result was assigned as negative for the related endpoint, and the factor set to 0 for this endpoint when calculating the Irritation Score (IS).

Scoring criteria for the acute effects and calculation of Irritancy Score (IS):

0 = no effect
1 = vasodilatation, slight haemorrhage (H)
2 = vessel lysis, strong haemorrhage (L)
3 = blood-coagulation, albumen-coagulation (C)

IS = 5 x (301-sec H)/300 + 7 x (301- sec L)/300 + 9 x (301- sec C)/ 300

H= observed start in seconds of haemorrhage reactions; L= observed start in seconds of vessel lysis, strong haemorrhage; C= observed start in seconds of blood - coagulation, albumen - coagulation

Data Interpretation:

Irritation Score (IS)

0-0.9 -> Non irritant
1-4.9 -> Slight irritant
5-8.9 -> Moderate irritant
9-21 -> Strong irritant

A test substance is considered to cause severe irritation when the IC value is greater than nine.
Irritation parameter:
other: irritation score (IS)
Run / experiment:
mean
Value:
0
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: A test substance is considered to cause severe irritation when the IC value is greater than nine.

Table 1: Summary of results, test item

 Egg  Effect  Effect detected after [sec]  Irritation Score (IS)
 9  1  > 300  
   2  > 300  
   3  > 300  0
 10  1  > 300  
   2  > 300  
   3  > 300  0
 11  1  > 300  
   2  > 300  
   3  > 300  0
 12  1  > 300  
   2  > 300  
   3  > 300  0

effect: 1 = vasodilatation, slight haemorrhage 2 = vessel lysis, strong haemorrhage 3 = blood-coagulation, albumen-coagulation

Interpretation of results:
other: negative
Executive summary:
The test item was tested in the in vitro assay applying the Hen´s Egg Test on the Chorio-Allantoic Membrane (HET-CAM) test method. This is a method that makes use of the chorioallantoic mambrane (CAM) of fertilized chicken eggs. For determination of acut effects on haemorrhage, lysis of blood vessels and coagulation the undiluted test item was directly applied onto the CAM. for 5 minutes. The Irritation Score (IS) value was calculated to be 0 for the test item which was interpreted as being non irritant. The results of the positive ( SDS 1% in physiologic saline) and negative (physiologic saline solution) controls confirmed the validity of the test system.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Due to the results with estrone no classification is required according to Regulation (EC) 1272/2008/EC (CLP), Annex I.