3-methoxyoestra-1,3,5(10)-trien-17-one

Endpoint summary

Description of key information

Acute toxicity oral: LD50 > 2000 mg/kg bw (Kurth 1994)

Acute toxicity dermal: LD50 > 2000 mg/kg bw (Kurth 1996)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

study was conducted prior to implementation of OECD TG 423

Deviations:

yes

Remarks:

The application of 2000 mg/kg to three animals was repeated with three animals of a different sex.

GLP compliance:

yes

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

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG
- Weight at study initiation: males: 94-104 g; females: 91-97 g
- Fasting period before study: ca. 18-18.5 hours
- Housing: 1/cage
- Diet (e.g. ad libitum): pell. Altromin R, ad libitum
- Water (e.g. ad libitum): demineralized acidified water, pH 2-3, ad libitum
- Acclimation period: 7 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23°C
- Humidity (%): 48-58%
- Photoperiod (hrs dark / hrs light): 12/12

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

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: day 8 and 14
- Necropsy of survivors performed: yes

Statistics:

Not applicable.

Key result

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

Conclusions:

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.

Executive summary:

In an acute oral toxicity study similar to OECD TG 423, fasted Wistar rats (3/sex) were given a single oral dose by gavage of estrone-methylether in Miglyol 812 at the limit dose 2000 mg/kg and observed for 14 days.

The administration of the test item 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

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13. July to 14. Aug 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

Deviations:

yes

Remarks:

3 instead of 5 animals/sex used

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG
- Weight at study initiation: males: 109-115 g; females: 96-107 g
- Fasting period before study: ca. 19 hours
- Housing: 1/cage
- Diet (e.g. ad libitum): pell. Altromin R, ad libitum
- Water (e.g. ad libitum): demineralized acidified water, pH 2-3, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-24°C
- Humidity (%): 42-60%
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

not specified

Vehicle:

physiological saline

Remarks:

900 mg NaCI + 85 mg Myrj® 53 ad 100 ml bidist. water

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

3/sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: start (day 1), on day 7 and at the end (day 14) of the study
- Necropsy of survivors performed: yes
- Other examinations performed: evaluation of local tolerance 24, 48 and 72 hours after the end of administration

Key result

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.

Conclusions:

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 the test item is above 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study similar to OECD TG 402 performed as a combined study on acute toxicity and on local tolerance Wistar rats (3/sex) (3/sex) were dermally exposed to estrone methylether in physiological saline for 24 hours at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days.

The administration of the test substance was tolerated without any clinical or macroscopic pathological finding. The dermal LD50 of the test substance is therefore > 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

In an acute oral toxicity study similar to OECD TG 423, fasted Wistar rats (3/sex) were given a single oral dose by gavage of estrone-methylether in Miglyol 812 at the limit dose 2000 mg/kg and observed for 14 days.

The administration of the test item 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 (Kurth, 1994).

 

In an acute dermal toxicity study similar to OECD TG 402 performed as a combined study on acute toxicity and on local tolerance Wistar rats (3/sex) (3/sex) were dermally exposed to estrone methylether in physiological saline for 24 hours at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days.

The administration of the test substance was tolerated without any clinical or macroscopic pathological finding. The dermal LD50 of the test substance is therefore > 2000 mg/kg body weight (Kurth, 1996).

 

Comparable to these results RTECS states a LD50 > 5000 mg/kg for acute oral toxicity in rats and mice for estrone (used as a source for read-across in other endpoints) and thereby supports the conclusion of no acute toxicity potential for these structural analogues. No inhouse studies with estrone on the endpoint acute toxicity were conducted.

 

In conclusion, estrone-3-methylether is not classified (Reg. (EC) No. 1272/2008) for both acute oral and acute dermal toxicity.

 

Acute toxicity studies for estrone-3-methylether

	Estrone-3-methylether (CAS 1624-62-0)
Study type	Acute oral	Comb. acute dermal & local tolerance
Study no./ Report no.	TX94.250 (draft version) Kurth, 1994	TX95190/ X052 (draft version) Kurth, 1996
GLP/ OECD TG/ deviations	GLP, equivalent to OECD 423 (limit study) Dev.: 2 sexes instead of 1; no individual animal reporting but means per sex with low & acceptable standard deviations scope of report limited related to actual TG 423 (acute toxic class method, adopted version Dec 2001) but sufficient for assessment	GLP, comparable to OECD 402 (limit study) & 404 Dev.: 2 sexes instead of 1, with n=3 animals per sex; no individual animal reporting but means per sex with low & acceptable standard deviations; scope of report limited related to actual TG 402 (2017) and TG 404 (July 2015), but sufficient for assessment
Species; animals/ group	Rat (Wistar), n=3 female/ male	Rat (Wistar), n=3 female/ male
Doses/ route/ schedule	2000 mg/kg (200 mg/ml) p.o., single treatment	2000 mg/kg, dermal (semi-occlusive), 24h-exposure, single treatment
Formulation	·         Batch no. 11427106; purity 96.1% (according to certificate of analysis no. 944647, dated 27 Jul. 94); information on stability in formulation not given ·         Microcristalline suspension in Miglyol 812; freshly prepared and administrated within 2h ·         Compound concentrations of 98-93% (applied to male rats) and 95% (applied to female rats) confirmed by HPLC with UV detection (analytical report SFR-KI 94113)	·         Batch no. 11427106; purity 96.1% (according to certificate of analysis no. 944647, dated 27 Jul. 94); information on stability in formulation not given ·         Suspension in 900 mg NaCI + 85 mg Myrj® 53 ad 100 ml bidist. water; freshly prepared ·         Compound concentrations of 112% (applied to male rats) and 101% (applied to female rats) determined by HPLC with UV detection (analytical report SFR-KI 95118)
observation period	14d	14 d, (for scoringof skin irritation parameters 24h, 48h 72h)
Results	·         Clinical signs: apathy and atactic gait after application; no findings from day 2 onwards ·         Increasing BW (mean values per sex) over time ·         No animal died ·         No findings within gross necropsy ·         LD50 > 2000 mg/kg	·         No local findings on skin at the application sites (no reddening, scab formation or swelling of the skin) ·         Compound tolerated without any clinical signs ·         Increasing BW (mean values per sex) over time ·         No animal died ·         No findings within gross necropsy ·         LD50 > 2000 mg/kg
Reliability	2	2

 

 

Justification for classification or non-classification

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