19-Norpregn-5(10)-ene-21-nitrile, 17-hydroxy-3-oxo-, (17.alpha.)-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 April 2002

Deviations:

yes

Remarks:

- 4 instead of 3 animals

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

17 alpha-Cyanomethyl-17 beta-hydroxy-5(10)-estren-3-one

EC Number:

613-855-5

Cas Number:

65928-65-6

Molecular formula:

C20 H27 N O2

IUPAC Name:

17 alpha-Cyanomethyl-17 beta-hydroxy-5(10)-estren-3-one

Constituent 2

Reference substance name:

612-855-5

IUPAC Name:

612-855-5

Details on test material:

Purity not specified

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, Germany
- Weight at study initiation: males: 4.0 - 4.3 kg; females: 4.3 - 5.2 kg
- Housing: individually in conventional scanbur cages
- Diet (e.g. ad libitum): pell. Ssniff ® K - H ad libitum
- Water (e.g. ad libitum): filtrated tap water ad libitum
- Acclimation period: ≥ 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24
- Humidity (%): 50-54
- 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):

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): Substance was not removed
SCORING SYSTEM: Evaluation of the local tolerance on the conjunctiva of the rabbits was performed according to the score system recommended for the EU (Annex to EEC guideline 92/69/EWG, dated 31 Jul 1992, for the 17th adaptation of the EEC guideline 67/548/EWG, B 5. Acute Toxicity (Eye irritation).Off J EEC, L383A, Luxembourg, 29 Dec 1992.).

TOOL USED TO ASSESS SCORE: Not reported.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 2

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 3

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 6

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 7

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 8

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 9

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 11

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 12

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 13

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 14

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 15

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 16

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 17

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Max. score:

4

Remarks on result:

not measured/tested

Remarks:

Chemosis score refers to the swelling of eye lids and nictating membranes. In this test only the swelling and reddening of the conjunctiva was 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)	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)	1	0	0	0.33
4 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	1	0	0.67
	Conjunctiva (swelling)	1	0	0	0.33

 

The control eyes were without findings.

 

Local findings after single administration of the test item into the conjunctival sac of the rabbit eye were slight to severe reddening and slight to moderate swelling of the conjunctivae in all animals on administration day. On day 2 slight reddening and/or swelling of the conjunctivae occurred in 3 out of 4 animals. All animals were without findings 72 hours after instillation of the test substance.

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 irritation of the conjunctivae from administration day on up to day 2 and were fully reversible 72 hours after administration. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters cornea and iris, 0.17 for conjunctival swelling and 0.42 for conjunctival reddening . According to EU classification criteria ZK 37877 need not be labelled as an eye irritant.

Executive summary:

In a primary eye irritation study according to OECD TG 405 (adopted 24 April 2002), 0.1 mL corresponding to 56.0 – 58.2 mg of 5-Dehydromethylketon (100% a.i.) as undiluted test material was instilled into the conjunctival sac of right eye of (2/sex) New Zealand White rabbits (Charles River, Kisslegg, Germany, males: 4.0-4.3 kg and females 4.3-5.2 kg). Animals were then observed for 4 days. Irritation was scored by the method described in the guideline.

Local findings after single administration of the test item into the conjunctival sac of the rabbit eye were slight to severe reddening and slight to moderate swelling of the conjunctivae in all animals on administration day. On day 2 slight reddening and/or swelling of the conjunctivae occurred in 3 out of 4 animals. All animals were without findings 72 hours after instillation of the test substance. In this study, the test item is not an eye irritant.