Pregn-4-ene-3,20-dione, 21-(acetyloxy)-6-fluoro-11-hydroxy-16-methyl-, (6.alpha.,11.beta.,16.alpha.)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug to Sep 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

22 March 1996

Deviations:

no

GLP compliance:

yes

Remarks:

- but a QA check was not performed

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

21-Acetoxy-6alpha-fluoro-11ß-hydroxy-16alpha-methyl-4-pregnene-3,20-dione

EC Number:

601-489-9

Cas Number:

1176-81-4

Molecular formula:

C24 H33 F O5

IUPAC Name:

21-Acetoxy-6alpha-fluoro-11ß-hydroxy-16alpha-methyl-4-pregnene-3,20-dione

Details on test material:

- Name of test material (as cited in study report): ZK 47525 (fluocortolone-A-acetate)
- Lot/batch No.: 87010241
- Stability under test conditions: Formulations were prepared freshly on application day and administrations were carried out within approx. 2 hours after formulation.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Weight at study initiation: males: 103-117 g; females: 100-106 g
- Fasting period before study: ca. 17.5 to 19 h
- Housing: conventional
- Diet (e.g. ad libitum): pell. Altromin® ad libitum
- Water (e.g. ad libitum): demineralized acidified water, pH 2-3 ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 52-64
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidest water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): The formulation was prepared freshly on application day and the administrations were carried out within approximately 2 h.

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: on day 8 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

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 after administration of 2000 mg/kg bw.

Clinical signs:

other: The administration of 2000 mgkg bw was tolerated without compound-related clinical findings.

Gross pathology:

Necropsy revealed no compound-related findings after 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 of the test item in male and female rats after a single i.g. administration is > 2000 mg/kg body weight.

Executive summary:

In an acute oral toxicity study according to OECD test guideline 423 (1996), groups of fasted, young adult Wistar rats (3/sex) were given a single oral dose of  Fluocortolone acetate (100% a.i.) in 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidest water at a dose 2000 mg/kg bw and observed for 14 days.

Oral LD50 Combined ≥ 2000 mg/kg bw

 

No Mortality nor clinical signs occurred in this limit test.

 

Fluocortolone is of low toxicity based on the LD50 in male and female Wistar rats.