13-β-ethyl-3-methoxygona-2,5(10)-dien-17-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June to July 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

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:

Gona-2,5(10)-dien-17-one, 13-ethyl-3-methoxy

IUPAC Name:

Gona-2,5(10)-dien-17-one, 13-ethyl-3-methoxy

Constituent 2

Reference substance name:

13-β-ethyl-3-methoxygona-2,5(10)-dien-17-one

EC Number:

219-034-4

EC Name:

13-β-ethyl-3-methoxygona-2,5(10)-dien-17-one

Cas Number:

2322-77-2

Molecular formula:

C20 H28 O2

IUPAC Name:

3-Methoxy-18-methyl-2,5(10)-estradien-17-on

Test animals

Species:

rat

Strain:

other: Han:WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG
- Weight at study initiation: 103-114 g (males), 100-107 g (females)
- Fasting period before study: ca. 18 hours
- Housing: 1 animal/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22°C
- Humidity (%): 54-64%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

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

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml (males), 100 mg/ml female
- Amount of vehicle (if gavage): 10 ml/kg (males); 20 ml/kg (females)
- Lot/batch no.: G/9324-1 (males); G/9358-1 (females)

- Rationale for the selection of the starting dose: A higher dosage than 2000 mg/kg was not tested in the present study since this dose level is established as the upper limit dose for classification and labelling requirements concerning dangerous substances.

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: day 1, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

none (limit test)

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died in the course of the study.

Clinical signs:

other: No compound related clinical findings.

Gross pathology:

Autopsy revealed no compound related findings.

Any other information on results incl. tables

No animal died in the course of the study. After application of 10 ml/kg of the formulation containing 200 mg test item/ml to the third animal it was established that this formulation was not homogeneous (although the vial was shaken between the applications a deposit of the substance was detected). Therefore the female animals were treated with a suspension containing 100 mg test item/ml with an application volume of 20 ml/kg. The applications to the male animals were not repeated because neither the female animals treated with a homogeneous formulation nor the male animals treated with the inhomogeneous suspension showed any compound-related findings. A single oral (gavage) application of 2000 mg/kg was tolerated without compound-related clinical findings. The body weight gain on days 7 and 14 was within the normal range for rats of this age and strain, which are routinely used in the laboratory. Autopsy revealed no compound-related findings.

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 signs, 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, Wistar rats, female and male weighing 100-107 and 103-114g, respectively, (3/sex) were given a single oral dose of D-ET-Dienon in 900 mg NaCI + 85 mg Myrj 53 ad 100 ml bidist. 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 Wistar rats.