Warfarin

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

no guideline available

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

129-06-0

IUPAC Name:

129-06-0

Constituent 2

Reference substance name:

Warfarin sodium

EC Number:

204-929-4

EC Name:

Warfarin sodium

Cas Number:

129-06-6

IUPAC Name:

sodium 2-oxo-3-(3-oxo-1-phenylbutyl)-2H-chromen-4-olate

Details on test material:

-Purity: not reported

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult females
- Weight at study initiation: 2336 g, 2166 g
- Housing: singly in suspended wire-mesh cages
- Diet (e.g. ad libitum): approx. 125 g high fiber rabbit chow
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22°C
- Humidity (%): 40-60%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hr light/12 hr dark

Test system

Vehicle:

not specified

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.01 g

Duration of treatment / exposure:

20 sec

Observation period (in vivo):

1 hr, 4 hr and days 1, 2, 3 and 7

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 20 sec after exposure

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Results 4

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

The test substance produced mild chemosis and moderate conjunctival redness with hemorrhaging of the conjunctiva and nictitating membrane in the treated washed and unwashed rabbit eyes. In addition, moderate iritis and copious blood-tinged discharge were observed in the treated unwashed eye. Both treated eyes were normal 7 days following treatment.

Other effects:

Both rabbits pawed their treated eye and 1 rabbit vocalized after instillation of the test substance.

Any other information on results incl. tables

Individual eye irritation Draize scores are presented below.

Rabbit Number 29045 (Unwashed)	1 Hour	4 Hours	1 Day	2 Days	3 Days	7 Days
Cornea Opacity	0	0	0	0	0	0
Cornea Area	0	0	0	0	0	0
Iris	0	1	0	0	0	0
Conjunctiva Redness	2	2	2C	2C	2C	0
Conjunctiva Chemosis	2	2	2	1	1	0
Conjunctiva Discharge	2H	3H	1H	0	0	0

Rabbit Number 29046 (Washed)	1 Hour	4 Hours	1 Day	2 Days	3 Days	7 Days
Cornea Opacity	0	0	0	0	0	0
Cornea Area	0	0	0	0	0	0
Iris	0	0	0	0	0	0
Conjunctiva Redness	2	2	2C	2C	2C	0
Conjunctiva Chemosis	2	2	1	1	1	0
Conjunctiva Discharge	0	0	0	0	0	0

H = Hemastix evaluations positive for blood

C = Hemorrhaging of the conjunctiva and the nictitating membrane

Applicant's summary and conclusion

Interpretation of results:

moderately irritating

Remarks:

Migrated information

Conclusions:

Under the conditions of this study, the test substance was a moderate eye irritant.

Executive summary:

The test substance was evaluated for acute eye irritation potential in 2 rabbits. Approximately 0.01 g of the test substance was instilled into the lower conjunctival sac of the right eye of each rabbit. Approximately 20 seconds after instillation, the treated and control eyes of 1 rabbit were washed. The treated and control eyes of the remaining rabbit were not washed. The eyes of the rabbits were examined on the day of treatment and on days 1, 2, 3, and 7 following treatment. 

 

The test substance produced mild chemosis and moderate conjunctival redness with hemorrhaging of the conjunctiva and nictitating membrane in the treated washed and unwashed rabbit eyes. In addition, moderate iritis and copious blood-tinged discharge were observed in the treated unwashed eye. Both treated eyes were normal 7 days following treatment.

 

Under the conditions of this study, the test substance was a moderate eye irritant.