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

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

223-564-1

EC Name:

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

Cas Number:

3962-66-1

Molecular formula:

C18H24O2

IUPAC Name:

(3aS,3bR,9bS,11aS)-11a-methyl-1H,2H,3H,3aH,3bH,4H,5H,6H,7H,8H,9H,9bH,10H,11H,11aH-cyclopenta[a]phenanthrene-1,7-dione

Constituent 2

Reference substance name:

5(10)-Estrene-3,17-dione

IUPAC Name:

5(10)-Estrene-3,17-dione

Constituent 3

Reference substance name:

Delta-5-Norandrostendion

IUPAC Name:

Delta-5-Norandrostendion

Test material form:

not specified

Details on test material:

Purity not specified

Test animals

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

Administration / exposure

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)

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.