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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

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:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

17 July 1992

Deviations:

yes

Remarks:

exposure time 24 hrs instead of 4 hrs, 6 animals instead of 3, few details in test description and reporting

Principles of method if other than guideline:

A combined study on acute dermal toxicity and on local tolerance was used to assess skin irritation/corrosion (comparable to OECD TG 402 and 404). The study design and reporting deviates from the current OECD TG 404, however, the study is considered sufficient for assessment of this endpoint. As described in ATP 96/54/EC ANNEX IV A, PART B: METHODS FOR THE DETERMINATION OF TOXICITY AND OTHER HEALTH EFFECTS, a strategy of testing for irritancy allows the non-performance of a test if an acute toxicity study by the dermal route has been conducted at the limit test dose with the substance (method B.3), and no skin irritation was observed, further testing for skin irritation (method B.4) may be unnecessary.

GLP compliance:

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

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): ad libitum pell. Altromin® R
- Water (e.g. ad libitum): ad libitum demineralized acidified water, pH 2-3
- Acclimation period: 7 days

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

Test system

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

other: liquid paraffin

Controls:

other: the untreated skin served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 556-564 mg/male animal or 408-414 mg/female animal


VEHICLE
- Amount(s) applied (volume or weight with unit): 556 and 564 mg + 0.6 ml vehicle
556 mg + 0.5 ml vehicle
408-414mg + 0.5 ml vehicle

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3 males and 3 females

Details on study design:

TEST SITE
- Area of exposure: not reported

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported


OBSERVATION TIME POINTS
day 1, 7 and 14

SCORING SYSTEM:
According to Annex I no. 1 of "Gefahrstoffverordnung, Verordnung zum Schutz vor gefährlichen Stoffen ( Gefahrstoffverordnung- GefStoffV), 6. Aufl., Stand Aug. 96

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Other effects:

none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg bw (556-564 mg/male and 408 -414 mg/female applied as a paste) was tolerated without any local irritations. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0. Therefore, local application of ZK 47525 (fluocortolone-A-acetate) was tolerated without irritation of the skin.

Executive summary:

In a primary dermal irritation study equivalent to OECD test guideline 404, young adult Wistar rats (3/sex) were dermally exposed to 556 and 564 mg + 0.6 mL vehicle, 556 mg + 0.5 mL vehicle, 408-414mg + 0.5 mL vehicle of Fluocortolone acetate (100% a.i.) in liquid paraffin for 24. Animals then were observed for 14 days.  Irritation was done according to the system recommended in Directive 67/548/EEC.

 

A single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg bw (556-564 mg/male and 408 -414 mg/female applied as a paste) was tolerated without any local irritations. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0.