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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10-15 April 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Minors deviations were observed but not considered to have compromised the validity or integrity of the study.
Principles of method if other than guideline:
Minor deviations observed: relative humidity recorded in the animal room was sometimes outside of the target ranges specified in the protocol, the animal's breeder was CEGAV, the animals were given 110 pelleted diet (instead of 112).
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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
- Sex: male
- Source: CEGAV (Saint Mars d'Egrenne, France)
- Age at study initiation: no data
- Weight at study initiation: 3.4 ± 0.2 kg
- Housing: individually in polystyrene cages.
- Diet (e.g. ad libitum): 110 pelleted diet (UAR, Villemoisson, Epinay sur orge, France), free access
- Water (e.g. ad libitum): water filtered, ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18+/-3°C
- Humidity (%): 30-70%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: control = untreated right eye
Amount / concentration applied:
A sinlge dose of 100 mg of the test substance first ground to a fine powder was introduced into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lower and upper eyelids held together for about one second to avoid any loss of test substance.
Duration of treatment / exposure:
one administration only
Observation period (in vivo):
10 days
Number of animals or in vitro replicates:
3
Details on study design:
Comment: not rinsed

ADMINISTRATION:
- Administration frequency: once
EXAMINATIONS:
- Ophthalmoscopic examination: Yes
- Scoring system: Draize's score
- Observation period: 1h, 24h, 48h and 72h after administration of the test substance
- Tool used to assess corneal opacification: examination under UV lamp after instillation of 1 or 2 drops of fluorescein (on day 2 and whenever if necessary).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Remarks:
(chemosis)
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0.8
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Mean individual scores : 1.0, 0.7 and 0.7
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0.8
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Mean individual scores : 1.0, 0.7 and 0.7
Irritation parameter:
conjunctivae score
Remarks:
(discharge)
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Mean individual scores : 0.3, 0.3 and 0.3
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0.1
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Remarks:
(intensity)
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Mean individual scores : 0.0, 0.3 and 0.3
Irritation parameter:
cornea opacity score
Remarks:
(area)
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Mean individual scores : 0.0, 0.3 and 0.3
Irritant / corrosive response data:
CONJUNCTIVAE:
- very slight or slight chemosis and redness (grade 1 or 2) were observed from day 1, in all animals and were completely resolved by 72-hour scoring interval
- a clear discharge (grade 1 or 2) was noted too from day 1 in all animals and were completely resolved by 48h-hour scoring interval.

IRIS: A slight iritis (grade 1) was noted in 1 animal on days 1 and 2.

CORNEAL OPACITY: A very slight corneal opacity (grade 1) was observed in 2 animals on day 2 only.

MEANS SCORES CALCULATED FOR EACH ANIMAL:
- For chemosis: 1.0, 0.7 and 0.7
- For redness of conjunctiva: 1.0, 0.7 and 0.7
- For iris lesions: 0.3, 0.0 and 0.0
- For corneal opacity: 0.0, 0.3 and 0.3.

Any other information on results incl. tables

Table 1: Individual ocular examination and mean values of the scores recorded at each reading (24, 48 and 72 hours) for each animal

 

Rabbit number

Region of eye

Description of ocular reactions

scores

Mean irritation score (1)

1h (D1)

24h (D2)

48h (D3)

72h (D4)

 

994

conjunctivae

Chemosis

2

2

1

0

1.0

Redness

2

2

1

0

1.0

Discharge

2

1

0

0

0.3

Iris

1

1

0

0

0.3

Corneal opacity

Intensity

0

0

0

0

0.0

Area

0

0

0

0

0.0

Other

Su

*

*

*

 

Fluorescein

/

U

/

/

 

 

576

conjunctivae

Chemosis

1

1

1

0

0.7

Redness

1

1

1

0

0.7

Discharge

2

1

0

0

0.3

Iris

0

0

0

0

0.0

Corneal opacity

Intensity

0

1

0

0

0.3

Area

0

1

0

0

0.3

Other

Su

Su

*

*

 

Fluorescein

/

U

U

/

 

 

577

conjunctivae

Chemosis

1

1

1

0

0.7

Redness

2

1

1

0

0.7

Discharge

2

1

0

0

0.3

Iris

0

0

0

0

0.0

Corneal opacity

Intensity

0

1

0

0

0.3

Area

0

1

0

0

0.3

Other

Su

Su

*

*

 

Fluorescein

/

U

U

/

 

 

(1)  mean of scores on days 2, 3 and 4

* : none

U: fluorescein batch No.D616

/: fluorescein not used

Su: residual test substance

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
not eye irritating
Conclusions:
Under these experimental conditions, the test substance CDBC is slightly irritant when administered by ocular route to rabbits.
Executive summary:

The potential of the test substance CDBC to induce ocular irritation was evaluated in rabbits according to OECD (405) and EC guidelines, and in compliance with the principles of GLP.

As possible irritant effects were anticipated, the test substance was administered to a single male rabbit in the first instance. Since the test substance was not severely irritant on this first animal, it was evaluated in twho other animals.

A single dose of 100 mg of the test substance, first ground to a fine powder, was introduced into the left conjunctival sac. The right eye was not rinsed after administration of the test substance. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after administration. The mean values of the scores for chemosis, redness of the conjunctivae, iris lesions and corneal opacity were calculated for each animal.

Very slight or slight conjunctival reactions (slight chemosis, slight redness of the conjunctivae and clear discharge) were observed in all animals from day 1: some of these reactions persisted up to day 3. A slight iritis was noted in one animal on days 1 and 2. A very slight corneal opacity was recorded in two animals, on day 2 only. Mean scores calculared for each animal aver 24, 48 and 72 hours were 1.0, 0.7 and 0.7 for chemosis, 1.0, 0.7 and 0.7 for redness of the conjunctiva, 0.3, 0.0 and 0.0 for iris lesions and 0.0, 0.3 and 0.3 for corneal opacity.

Under these experimental conditions, the test substance CDBC is slightly irritant when administered by ocular route to rabbits.