Oestr-5(10)-ene-3,17-dione

Endpoint summary

Description of key information

LD50 oral (rat): > 2000 mg/kg bw [Ihara 2004]
LD50 dermal (rat): > 2000 mg/kg bw [Ihara 2004]

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:

from January to February 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 22 March 1996

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Jcl:SD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CLEA Japan, Inc.
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 84-92 g (males), 97-98 g (females)
- Fasting period before study: 19 hours
- Housing: 1 animal/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 0.085% Myrj® 53 + 0.9% NaCl in water

Details on oral exposure:

- Application volume: 2.0 mL/100g bw
- Application concentration: 100 mg/mL
- Rationale for the selection of the starting dose:
Dose levels of 2000, 200 and 25 mg/kg were set in accordance with the acute toxic class method (OECD guideline no. 423). The LD50 in rats after oral administration of the final product of the substance, is >2000 mg/kg. The LD50 of the structure of which resembles that of the substance, is between 200 mg/kg and 2000 mg/kg (probably near 2000 mg/kg). Since the toxic potential of test item is supposed to be not high, in Step I, 2000 mg/kg was administered in males. In Step II, 2000 mg/kg was administered in females since there were no deaths in males after administration. The lower doses were not administered, since no deaths were observed in either males or females at 2000 mg/kg.
VEHICLE
- Concentration in vehicle: 0.085% Myrj® 53 + 0.9% NaCl in water
- Amount of vehicle (if gavage): 2.0 mL
- Lot/batch no. (if required): Myrj® 53: Lot No. 205A0327; Physiological saline: Lot No. MOD76
MAXIMUM DOSE VOLUME APPLIED: 2 mL

Doses:

2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least once daily (clinical signs, mortality) or once weekly (weighing)
- Necropsy of survivors performed: yes

Statistics:

none (limit test)

Key result

Sex:

male/female

Dose descriptor:

other: LD50 cut-off

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died.

Clinical signs:

other: No compound-related findings were observed in any of the animals.

Gross pathology:

No compound-related findings were found out.

Conclusions:

A single oral administration of the test substance by gavage to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, clinical findings, effects on body weight gain and gross pathological findings. According to OECD TG 423 the oral LD50 of the test substance is therefore > 2000 mg/kg body weight.

Executive summary:

In an acute oral toxicity study similar to OECD TG 423 (adopted 22 March 1996), groups of fasted, Jcl:SD rats, female and male weighing 97-98 and 84-92g, respectively, (3/sex) were given a single oral dose of Delta-5-Norandrostendion 0.085% Myrj® 53 + 0.9% NaCl in water at a dose of 2000 mg/kg bw and observed for 14 days.

 

Oral LD50 Combined => 2000 mg/kg bw

Limit test

 

No mortality occurred during the test

 

There were no treatment related clinical signs, necropsy findings or changes in body weight.

 

The test item is of low Toxicity based on the LD50 in male and female Jcl:SD rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

This study is GLP compliant and is of high quality (Klimisch Score = 1).

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:

from March to April 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987

Deviations:

yes

Remarks:

- 3 instead of 5 animals/sex used

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Jcl:SD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CLEA Japan, Inc.
- Age at study initiation: 7 weeks (male), 10-11 weeks (female)
- Weight at study initiation: 257-288 g (male), 264-272 g (female)
- Housing: 1 animal/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.7-22.8
- Humidity (%): 42-57
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

other: liquid paraffin

Details on dermal exposure:

TEST SITE
- Area of exposure: 4 x 9 cm
- % coverage: 10% of body surface
- Type of wrap: gauze pad

REMOVAL OF TEST SUBSTANCE
- Washing: rinsed out with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): weighted test item in 1 mL liquid paraffin per animal
- Lot no.: 2Y28

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least once daily (clinical signs, mortality) or once weekly (weighing)
- Necropsy of survivors performed: yes

Statistics:

none (limit test)

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died in the course of the study.

Clinical signs:

other: No compound-related findings were observed.

Gross pathology:

No compound-related findings were observed.

Conclusions:

A single dermal administration of the test substance to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, compound-related clinical findings, effects on body weight gain and gross pathological findings. According to OECD TG 402 the dermal LD50 of the test substance is therefore > 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study similar to OECD TG 402 (adopted 24 February 1987), groups of young adult Jcl:SD rats (3/sex) were dermally exposed to Delta-5-Norandrostendion in liquid paraffin for 24 hours at a dose 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD50 Combined = > 2000 mg/kg bw

No mortality occurred during the limit test.

The test item is of low Toxicity based on the combined LD50 value of > 2000 mg/kg bw.

There were no treatment related clinical signs, necropsy findings or changes in body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

This study is GLP compliant and is of high quality (Klimisch Score = 1).

Additional information

In an acute oral toxicity study similar to OECD TG 423 (adopted 22 March 1996), groups of fasted, Jcl:SD rats, female and male weighing 97-98 and 84-92g, respectively, (3/sex) were given a single oral dose of Delta-5-Norandrostendion 0.085% Myrj® 53 + 0.9% NaCl in water at a dose of 2000 mg/kg bw and observed for 14 days.

Oral LD50 Combined => 2000 mg/kg bw

Limit test

No mortality occurred during the test

There were no treatment related clinical signs, necropsy findings or changes in body weight.

The test item is of low Toxicity based on the LD50 in male and female Jcl:SD rats.

 

In an acute dermal toxicity study similar to OECD TG 402 (adopted 24 February 1987), groups of young adult Jcl:SD rats (3/sex) were dermally exposed to Delta-5-Norandrostendion in liquid paraffin for 24 hours at a dose 2000 mg/kg bw. Animals then were observed for 14 days.

Dermal LD50 Combined = > 2000 mg/kg bw

No mortality occurred during the limit test.

The test item is of low Toxicity based on the combined LD50 value of > 2000 mg/kg bw.

There were no treatment related clinical signs, necropsy findings or changes in body weight.

Justification for classification or non-classification

Based on the study results a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.