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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Oct 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 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 February 1987

Deviations:

yes

Remarks:

4 instead of 3 animals

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): fluocortolone-A-acetate (ZK 47525)
- Lot/batch No.: 87010241

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, Kisslegg
- Weight at study initiation: males: 3.3 - 4.1 kg; females: 3.7 - 3.9 kg
- Housing: individually in metal cages under conventional conditions
- Diet (e.g. ad libitum): pell. Altromin® K ad libitum
- Water (e.g. ad libitum): demineralized water ad libitum
- Acclimation period: > 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 60-62
- Photoperiod (hrs dark / hrs light):12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye, which remained untreated, served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL corresponding to 39.3 - 42.6 mg

Duration of treatment / exposure:

test substance remained in the eye (eye was not rinsed)

Observation period (in vivo):

4 days

Number of animals or in vitro replicates:

2 males and 2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

SCORING SYSTEM: according to guideline

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Chemosis score was not determined, reddening and swelling was only investigated for the iris

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 4

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

mean

Time point:

24/48/72 h

Score:

0.37

Max. score:

3

Reversibility:

fully reversible within: 4 days

Results 5

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

mean

Time point:

24/48/72 h

Score:

0.08

Max. score:

4

Reversibility:

fully reversible within: 3 days

Any other information on results incl. tables

Table 1: Results of the study

		Irritant effects (score)
Animal no. (sex)	Irritation parameter	24 h	48 h	72 h	Mean scores
1 (M)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	1	0	0.67
	Conjunctiva (swelling)	0	0	0	0.0
2 (M)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	0	0	0	0.0
	Conjunctiva (swelling)	0	0	0	0.0
3 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	0	0	0.33
	Conjunctiva (swelling)	0	0	0	0.0
4 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	0	0	0.33
	Conjunctiva (swelling)	1	0	0	0.33

The control eyes were without findings.

The single application of 0.1 mL ZK 47525 (corresponding to 39.3 - 42.6 mg) into the conjunctival sac of the left eye led to slight to moderate reddening and slight to severe swelling of the conjunctivae on the administration day 1. On days 2 and 3 only slight reddening and/or swelling was observed. On day 4 (72 h after end of exposure) all animals were without findings.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In a local tolerance test on the rabbit eye according to OECD TG 405 a single application of the test substance into the conjunctival sac provoked slight conjunctival reddening and/or swelling on study days 2 and 3. On day 4 (72 h after end of exposure) all animals were without findings. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0.0 for the parameters cornea and iris, 0.37 for conjunctival reddening as well as 0.08 for conjunctival swelling. According to EU classification criteria ZK 47525 (fluocortolone-A-acetate) need not be labelled as an eye irritant.

Executive summary:

In a primary eye irritation study according to OECD test guideline 405 (1987), 0.1mL Fluocortolone acetate (100% a.i.) was instilled into the conjunctival sac of the left eye of young adult New Zealand White rabbits (2/sex). Animals then were observed for 4 days.  Irritation was scored by the method recommended by the guideline.

 

The single administration of 0.1 ml Fluocortolone acetate (= 39.3 - 42.6 mg) into the conjunctival sac of the left eye led to slight to moderate reddening and slight to severe swelling of the conjunctivae on the administration day. On days 2 and 3, only slight reddening and/or swelling was observed. On day 4, all animals were without finding. According to the system of evaluation recommended for EU (1), the mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after administration were 0 tor the cornea and iris, 0.33 for conjunctival reddening and 0.08 for the conjunctival swelling., thus, Fluocortolone acetate does not need to be classified according to Regulation 1272/2008 (CLP) with regard to eye irritation.