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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).

No acute toxicity studies were conducted with estrone; read across approach with results of studies 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 mammalian 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:

Acute oral toxicity:

The single oral administration of the test item to male and female Wistar rats at the dose of 2000 mg/kg resulted in transient clinical signs (apathy and atactic gait). All animals were without treatment-related findings from Day 2 onwards. No compound-related macroscopic findings were seen. The acute oral toxicity of the test item in rats is above 2000 mg/kg body weight.

Acute dermal toxicity:

The single dermal administration of the test item to male and female Wistar rats at the dose of 2000 mg/kg was tolerated without any clinical or macroscopic pathological findings. The acute dermal toxicity of the test item is above 2000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29. Sep to 02. Nov 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
- Solubility and stability of the test substance in the solvent/vehicle: The mycrorystalline suspensions were prepared fresh on application day for immediate application and administrations were carried out within approximately 2 hours after preparation. The stability of the test item was verified analytically. In addition all samples are considered prepared correctly with regard to the results of analysis.
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: Miglyol 812
Doses:
2000 mg/kg
No. of animals per sex per dose:
3/sex
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality
Clinical signs:
other: Transient clinical signs (apathy and atactic gait). All animals were without treatment-related findings from day 2 onwards.
Gross pathology:
no effects observed
Interpretation of results:
other: no substance related mortality observed
Conclusions:
The acute oral toxicity of estrone-methylether in rats is above 2000 mg/kg body weight.
Executive summary:

The single oral administration of estrone-methylether to male and female Wistar rats at the dose of 2000 mg/kg resulted in transient clinical signs (apathy and atactic gait). All animals were without treatment-related findings from Day 2 onwards. No compound-related macroscopic findings were seen. The acute oral toxicity of estrone-methylether in rats is above 2000 mg/kg body weight.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
No acute toxicity studies were conducted with estrone; read across approach with results of studies 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 mammalian 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
Limit test:
yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
other: Transient clinical signs (apathy and atactic gait). All animals were without treatment-related findings from day 2 onwards.
Gross pathology:
no effects observed
Interpretation of results:
other: no substance related mortality observed
Conclusions:
The acute oral toxicity of estrone-methylether in rats is above 2000 mg/kg body weight.
Executive summary:

The single oral administration of the test item to male and female Wistar rats at the dose of 2000 mg/kg resulted in transient clinical signs (apathy and atactic gait). All animals were without treatment-related findings from Day 2 onwards. No compound-related macroscopic findings were seen. The acute oral toxicity of estrone-methylether in rats is above 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13. July to 14. Aug 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
not specified
Vehicle:
physiological saline
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
3/sex
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality occurred
Clinical signs:
other: The test substance was tolerated without any clinical findings.
Gross pathology:
The test substance was tolerated without any macroscopic pathological findings.
Interpretation of results:
other: no substance related mortality observed
Conclusions:
The acute dermal toxicity of estrone methylether is above 2000 mg/kg body weight.
Executive summary:

The single dermal, 24 h-administration of the test item to male and female Wistar rats at the dose of 2000 mg/kg was tolerated without any clinical or macroscopic pathological findings. The acute dermal toxicity of the test item is above 2000 mg/kg body weight.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
No acute toxicity studies were conducted with estrone; read across approach with results of studies 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. Therefore, it is possible to use knowledge of estrone methylether for the assessment of estrone:
Reason / purpose for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality occurred
Clinical signs:
other: The test substance was tolerated without any clinical findings.
Gross pathology:
The test substance was tolerated without any macroscopic pathological findings.
Interpretation of results:
other: no substance related mortality observed
Conclusions:
The acute dermal toxicity of estrone methylether is above 2000 mg/kg body weight.
Executive summary:

The single dermal, 24 h-administration of estrone methylether to male and female Wistar rats at the dose of 2000 mg/kg was tolerated without any clinical or macroscopic pathological findings. The acute dermal toxicity of estrone methylether is above 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

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).

Additionally results of acute toxicity studies with estrone are cited in RTECS database (Aug 2011):

A acute oral toxicity study in rats results in LD50 >5000 mg/kg [Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (6), p. 25, 1994 (TOVEFN)]

A acute oral toxicity study in mice results in LD50: >5000 mg/kg [Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (6), p. 25, 1994 (TOVEFN)]

Acute inhalation toxicity study in rats results in effects on spermatogenesis (including genetic material, sperm morphology, motility, and count) with a TCLo: 0.005 mg/m3/4H; LD50 is not reported [Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (6), p. 25, 1994 (TOVEFN)]

Acute inhalation toxicity study in rats results in effects on testes, epididymis and sperm duct with a TCLo: 0.01 mg/m3/4H; LD50 is not reported [Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (6), p. 25, 1994 (TOVEFN)]

Acute dermal toxicity study in rats results in endocrine effect on menstrual cycle with TDLo: 0.1 mg/kg; LD50 is not reported [Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (6), p. 25, 1994 (TOVEFN)]

Acute inhalation toxicity data in rats result in endocrine effect on menstrual cycle with TCLo: 0.01 mg/m3; LD50 is not reported [Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (6), p. 25, 1994 (TOVEFN)]

Justification for classification or non-classification

Based on the data for surrogate no classification for acute toxicity (oral, dermal) according to Regulation (EC) No. 1272/2008 (CLP) is required for estrone.