Desmedipham

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-11-24 to 1991-03-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Desmedipham

EC Number:

237-198-5

EC Name:

Desmedipham

Cas Number:

13684-56-5

Molecular formula:

C16 H16 N2 O4

IUPAC Name:

ethyl 3´-phenylcarbamoyloxycarbanilate

Test material form:

solid: particulate/powder

Details on test material:

The test material is Desmedipham but the purity has not been specified.

Specific details on test material used for the study:

The test material is in a white powder form.

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 adults.
- Weight at study initiation: Not provided.
- Housing: Individually in aluminium cages with grid floors beneath which were peat moss filled trays.
- Diet: Standard Rabbit Diet, ad libitum.
- Water: ad libitum
- Acclimation period: 12 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-19
- Mean Relative Humidity (%): 57
- Air changes (per hr): Not provided.
- Photoperiod: 12 h light/dark cycle (light hours 0700-1900 h).

The rabbits were uniquely identified within the study by an indelible number on the inner surface of the ear.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 100 mg

Instillation of the test material was by the following technique:
The rabbit was held firmly but gently and the test material placed into the right eye by gently pulling the lower eyelid away from the eyeball to form a sac into which the test material was dropped. The lids were then gently held together for 1-2 seconds.

Duration of treatment / exposure:

Single instillation

Observation period (in vivo):

One rabbit was treated first and observed up to 24 h after instillation for signs of severe irritation. As none were noted, the remaining 2 rabbits were then treated. The eyes were examined for irritation and ocular reactions were recorded 1, 24, 48 and 72 h after instillation.

Number of animals or in vitro replicates:

3 animals

Details on study design:

Approximately 24 h before test commencement, both eyes of the rabbits were examined and only animals with no ocular defects were used in the test.

SCORING SYSTEM:

TOOL USED TO ASSESS SCORE: The eyes were examined for irritation, using a hand held magnifier and pen torch.

OECD Recommended Scoring System:

CORNEA:
1- Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity - 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible - 1
Easily discernible translucent area, details of iris slightly obscured - 2
Nacreous area, no details of iris visible, size of pupil barely discernible - 3
Opaque cornea, iris not discernible through the opacity - 4

2- Area of Opacity
A quarter (or less) but not more - 1
Between a quarter and a half - 2
Between half and three quarters - 3
Between three quarters and the whole surface - 4

IRIS:
Normal - 0
Markedly deepened folds, congestion, swelling, moderate circumcorneal hyperaemia or injection (any of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive) - 1
No reaction to light, haemorrhage, gross destruction (any or al 1 of these) - 2

CONJUNCTIVAE:
1- Redness (refers to palpebral and bulbar conjunctivae):
Blood vessels normal - 0
Some blood vessels definitely hyperaemic (injected) - 1
Diffuse, crimson colour, individual vessels not easily discernible - 2
Diffuse beefy red - 3

2- Chemosis (lids and/or nictitating membranes):
No swelling - 0
Any swelling above normal (including nictitating membranes) - 1
Obvious swelling with partial eversion of lids - 2
Swelling with lids about half closed - 3
Swelling with lids more than half closed - 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

3

Reversibility:

fully reversible within: persisting until 48 h in one treated eye. All treated eyes were normal by 72 h post instillation.

Remarks on result:

probability of weak irritation

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Details of reaction scores are given in the table below.

No corneal or iridial responses were noted.

Slight conjunctival redness and a slight discharge were noted 1 h post instillation with slight redness persisting until 48 h in one treated eye. All treated eyes were normal by 72 h post instillation.

Any other information on results incl. tables

Table 1: Desmedipham: Acute Eye Irritation Test in Rabbits Reaction Scores

Area of Eye

Observation Time/ Animal /Sex/Score

1 h

24 h

48 h

72 h

4/male

5/male

6/male

4/male

5/male

6/male

4/male

5/male

6/male

4/male

5/male

6/male

Cornea: degree/opacity area/opacity   Iris   Conjunctivae: redness chemosis   Discharge

0 0   0     1 0   -

0 0   0     1 0   SL

0 0   0     0 0   -

0 0   0     0 0   -

0 0   0     1 0   -

0 0   0     0 0   -

0 0   0     0 0   -

0 0   0     1 0   -

0 0   0     0 0   -

0 0   0     0 0   -

0 0   0     0 0   -

0 0   0     0 0   -

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Desmedipham is practically non-irritant to rabbit eyes and does not require classification for eye irritation in any category according to the CLP criteria.

Executive summary:

The eye irritation potential of Desmedipham, was investigated in 3 New Zealand White rabbits. Slight conjunctival redness and a slight discharge were noted at 1 h post instillation with slight redness persisting until 48 h post instillation in one treated eye. Desmedipham is practically non-irritant to rabbit eyes and does not require classification for eye irritation in any category according to the CLP criteria.