(17α)-17-hydroxy-3-oxoandrost-4-ene-17-carbonitrile

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

other information

Study period:

Jan 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well reported GLP study with some substance loss during application

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

17 beta-cyano-17 alpha-hydroxy-4-androsten-3-on

IUPAC Name:

17 beta-cyano-17 alpha-hydroxy-4-androsten-3-on

Details on test material:

- Name of test material (as cited in study report): ZK 74.804
- Batch No.: BA 76.700

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye served as control

Duration of treatment / exposure:

test substance remained in the eye, eye was not rinsed

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

2 males and 2 females

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.6

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Any other information on results incl. tables

Results of the study

		Irritant Effects (Score)
Animal		24 h	48 h	72 h	Mean scores
1(M)	Cornea	0	0	0	0.0
	Iris	1	0	0	0.3
	Conjunctiva (reddening)	2	0	0	0.7
	Conjunctiva (swelling)	1	0	0	0.3
2 (M)	Cornea	0	0	0	0.0
	Iris	1	0	0	0.3
	Conjunctiva (reddening)	1	0	0	0.3
	Conjunctiva (swelling)	0	0	0	0.0
3 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	2	0	0	0.7
	Conjunctiva (swelling)	1	0	0	0.3
4 (F)	Cornea	0	0	0	0.0
	Iris	1	0	0	0.3
	Conjunctiva (reddening)	2	0	0	0.7
	Conjunctiva (swelling)	1	0	0	0.3

On the application day all animals showed predominantly moderate local incompatibility reactions on the conjunctiva (including concjunctiva tertia and sclera) such as reddening, swelling and vessel injections. Additionally, all animals showed predominantly slight vessel injections of the iris, eyelid closure, slight secretion and reddening of the skin of the eyelid. On day 2 of the test 3 animals showed slight swelling of the margin of the eyelid. The findings decreased on day 2 and 3 of the test and all animals were without findings on day 4.

Applicant's summary and conclusion

Executive summary:

The single administration of AD-Cyanhydrin into the right eye of 2 male and 2 female rabbits with a volume of 100 mg/eye resulted in moderate local incompatibility reactions on the conjunctiva (including concjunctiva tertia andsclera) such as reddening, swelling and vessel injections and slight vessel injections of the iris, eyelid closure, slight secretion and reddening of the skin of the eyelid on the application day. All findings were transient with decreasing intensity from day 2 onwards and all animals were without findings on day 4.

The above mentioned findings were classified at that time as moderate local incompatibility reactions but according to the system of evaluation recommended for EU, the mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after administration were 0 for the cornea, 0.3 for the iris and conjuntival swelling and 0.6 for conjunctival reddening. Therefore, according to EU classification criteria the test substance is not eye irritating. However, it has to be mentioned that due to the low bulk density of the test substance the application volume was too big and a considerable amount of the test substance was lost after application. The remaining substance on the conjunctiva stuck together forming lumps of various size. Therefore, it was assumed that the observed findings were provoked by the physical characteristics of the compound and it was decided to perform another study using 10 mg test substance/eye only.