9beta,11beta-Epoxy-6alpha-fluoro-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

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

Remarks:

- but a QA check was not performed

Test material

Test material information

Constituent 1

Reference substance name:

9beta, 11beta-Epoxy-6alpha-fluoro-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione

Cas Number:

65535-29-7

Molecular formula:

C27 H35 F O5

IUPAC Name:

9beta, 11beta-Epoxy-6alpha-fluoro-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione

Test material form:

solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Schriever
- Weight at study initiation: males: 2.8-3.3 kg; females: 2.6-3.3 kg
- Housing: Individually in conventional metal cages
- Diet (e.g. ad libitum): pell. Altromin® K ad libitum
- Water (e.g. ad libitum): demineralized water ad libitum
- Acclimation period: > 14 days; during this period a diet containing 0.03%
sulfaquinoxaline was offered for 7 consecutive days as coccidiosis prophylaxis; the animals received Jacutin® emulsion into the meatus acusticus externus for prophylaxis against mite infection of the ear and were vaccinated against rabbit haemorrhagic disease (Arvilap®)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 56-60
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

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

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

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

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

2 males and 2 females

Details on study design:

SCORING SYSTEM: Evaluation of the local tolerance on the conjunctiva of the rabbit after a single application was performed according to the score system recommended for the EU.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1-#4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 3

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 4

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 5

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 6

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 6 d

Results 7

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 6 d

Results 8

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 6 d

Results 9

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 10

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 11

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 12

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 13

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 14

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Max. score:

4

Remarks on result:

not measured/tested

Remarks:

In the present study only swelling of the conjunctivae was measured, swelling of eye lids and nictating membranes was not reported

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)	2	0	0	0.67
	Conjunctiva (swelling)	3	0	0	1.0
2 (M)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	2	1	1	1.33
	Conjunctiva (swelling)	0	0	0	0.0
3 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	2	1	1	1.33
	Conjunctiva (swelling)	0	0	0	0.0
4 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	2	2	1	1.67
	Conjunctiva (swelling)	0	0	0	0.0

 

The control eyes were without findings.

 

The single application of 0.1 mL ZK 50992 (corresponding to 61-71 mg) into the conjunctival sac of the right eye led to moderate to severe reddening and vascular injection and slight to moderate swelling of the conjunctivae on the administration day 1. Slight to moderate reddening and/or swelling, which gradually subsided were observed up to day 6.

Applicant's summary and conclusion

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 to moderate reddening and/or swelling, which gradually subsided up to day 6. On day 7 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, 1.25 for conjunctival reddening as well as 0.25 for conjunctival swelling. Thus, the test item is not considered as an eye irritant.

Executive summary:

In a primary eye irritation study according to OECD TG 405 (adopted 24 February 1987), 0.1 mL corresponding to 61-71 mg of Epoxide-Valerate was instilled into the conjunctival sac of the right eye of young adult female and male New Zealand White rabbits (2/sex) and the animals were observed for 7 days. The eyes were not washed. Irritation was scored by the method described in the guideline.

 

The single application of 0.1 mL of the test item (corresponding to 61-71 mg) into the conjunctival sac of the right eye led to moderate to severe reddening and vascular injection and slight to moderate swelling of the conjunctivae on the administration day 1. Slight to moderate reddening and/or swelling, which gradually subsided were observed up to day 6. In this study, the test item is not an eye irritant.