Estradiol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001

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:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

according to Japanese Guidelines for Toxicity Studies of Drugs, Notification 1-24, 1989

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Estradiol

EC Number:

200-023-8

EC Name:

Estradiol

Cas Number:

50-28-2

Molecular formula:

C18H24O2

IUPAC Name:

estra-1,3,5(10)-triene-3,17-diol

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

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: 70-120 g
- Fasting period before study: 16-20 h
- Housing: individually
- Diet (e.g. ad libitum): Solid food CE-2, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 11 days
- Method of randomisation in assigning animals to test and control groups: Stratified sequenced randomization

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 55 ± 10%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

Formulation in 0.5% CMC-Na + 0.04% Tween-80

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 mg/mL
- Amount of vehicle (if gavage): 4.0, 1.0, 1.9, 4.0 mL/100 g
- Purity: 0.5% CMC-Na + 0.04% Tween-80

MAXIMUM DOSE VOLUME APPLIED: 4.0 mL/100 g


CLASS METHOD
- Rationale for the selection of the starting dose:
Doses were chosen based on the results of previous combination study in rats with E2 + gestodene.

Doses:

0, 500, 950, 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Remarks:

no positive control one vehicle control

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Survival: daily; Body weight: Day 0, 1, 2, 3, 6, 10, 14; Clinical signs: on day 0 (after 30 min, 1h, 3h, 5h, the next day two times and afterwards once a day.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality occurred

Clinical signs:

other: no clinical signs were reported

Gross pathology:

No findings within gross necropsy

Applicant's summary and conclusion

Conclusions:

Inj the present study which was conducted equivalent to OECD test guideline 423, female Sprague-Dawley rats (5/group) were orally administered a single dose Estradiol and were observed for the following 14 days. The doses applied were. 0, 500, 950, 2000 mg/kg bw. No mortality occurred in any of the groups, no clinical signs were observed, no gross abnormalties were observed at necrospy. However, there was a slight reduction in body weight and food consumption in the treated animals as compared to the control animals. Based on these results the LD50 value for acute oral toxicity is considered > 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study similar to OECD test guideline 423, groups of fasted, 4-5 weeks old female Sprague Dawley rats (5/group) were given a single oral dose of E§stradiol in 0.5% CMC-Na + 0.04% Tween-80 at doses of 0, 500, 950, 2000 mg/kg bw and observed for 14 days.

 

Oral LD50 Females > 2000 mg/kg bw

No mortality occurred during the test

 

Estradiol is of low Toxicity based on the LD50 in female Sprague Dawley rats.

There were no treatment related clinical signs or necropsy findings. However, body weight was slightly decreased in the treatment groups as compared to the control group animals.