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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same 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 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987

Deviations:

yes

Remarks:

3 instead of 5 animals/sex used

GLP compliance:

yes

Remarks:

- but a QA check was not performed

Test type:

standard acute 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
- Weight at study initiation: males: 278-282 g; females: 204-207g
- Housing: individually under conventional conditions
- Diet (e.g. ad libitum): pell. Altromin® R ad libitum
- Water (e.g. ad libitum): demineralized acidified water, pH 2-3 ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 64-66
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: liquid paraffin

Details on dermal exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
step I: 556 and 564 mg ZK 47525 + 0.6 mL vehicle
step I: 556 mg ZK 47525 + 0.5 mL vehicle
step II: 408-414mg ZK 47525 + 0.5 mL vehicle

- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

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
- Clinical signs including body weight: The comparison of the individual values revealed a decrease in body weight gain in male animals dosed with 2000 mg of the test item between day 1 and day 7 of the test. Two male animals (nos. 232; 234) showed even a body weight loss at this time-point. On day 14 the above-mentioned animals showed a body weight gain in the normal range wh ich was routinely observed in our laboratory. No compound-related findings were observed in body weight gain in female animals.

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: A single dermal application of 2000 mg/kg was tolerated without compound-related 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 ZK 47525 in male and female rats after a single dermal application is > 2000 mg/kg body weight. Local application was tolerated without irritation of the skin.

Executive summary:

In an acute dermal toxicity study according to OECD test guideline 402, groups of young adult Wistar rats (3/sex) were dermally exposed to Fluocortolone acetate (100% a.i) in liquid paraffin for 24 hours at a dose of 2000 mg/kg bw.  Animals then were observed for 14 days.

 

Dermal LD50 Combined ≥ 2000 mg/kg bw

 

No mortality nor clinical signs occurred in this limit test.

 

Fluocortolone acetate is of low Toxicity based on the LD50 value for male and female Wistar rats.

The single dermal administration of 2000 mg of the test item/kg was tolerated without compound-related clinical findings.

The comparison of the individual values revealed a decrease in body weight gain in male animals dosed with 2000 mg of the substance between day 1 and day 7 of the test. Two male animals (nos. 232; 234) showed even a body weight loss at this time-point. On day 14 the above-mentioned animals showed a body weight gain in the normal range which was routinely observed in our laboratory. No compound-related findings were observed in body weight gain in female animals.