Norethisterone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

4. to 31. Dec 1968

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented study, no GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1969

Report date:

1969

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Norethisterone enantate

EC Number:

223-326-7

EC Name:

Norethisterone enantate

Cas Number:

3836-23-5

Molecular formula:

C27H38O3

IUPAC Name:

17-ethynyl-3-oxoestr-4-en-17-yl heptanoate

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Hagemann
- Weight at study initiation: 90-100 g
- Fasting period before study: 18 h
- Housing: 5 per cage, Macrolon type III; conventional
- Diet (e.g. ad libitum): Altromin R, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 17 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 55-65
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: benzylbenzoate + castor oil (4+6)

Details on oral exposure:

VEHICLE
- benzyl bezoate / castor oil
- Concentration in vehicle: 50 g/100 mL
- Dose volume: 0.6 ml/100 g bw

Doses:

3000 mg/kg

No. of animals per sex per dose:

10 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 22 days
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Based on:

test mat.

Mortality:

1/10 female died on day 3

Clinical signs:

1/10 female was comatose on day 1-2 and died on day 3;
the other animals did not show any clinical signs

Gross pathology:

1/10 females showed stomach overloading, stomach hyperaemia, enteritis;
no other effects were noted at necropsy

Any other information on results incl. tables

The test substance was tolerated without any compound-related clinical signs. One female rat died on day 3. In all sacrifices animals no macroscopic pathological signs were observed

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 female rat (oral) norethisterone enanthate > 3000 mg/kg body weight

Executive summary:

The single oral administration of ZK 5410 to 10 rats/sex at a dose of 3000 mg/kg was tolerated without any compound-related clinical signs. One female rat died on day 3. In all sacrificed animals no macroscopic pathological signs were observed.