Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 06 aug 2003 to 04 dec 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study, OECD TG 405 compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Temperature and humidity sometimes outsides of the target.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France.
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 3.4 kg.
- Housing: The animal was housed in a polystyrene cage (48.2 cm x 58 cm x 36.5 cm) equipped with a food container and a water bottle.
- Diet: free access to 110 pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France).
- Water: Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
- Acclimation period: at least 5 days before the beginning of the study.


ENVIRONMENTAL CONDITIONS
• temperature: 18 ± 3°C
• relative humidity: 30 to 70%
• light/dark cycle: 12 h/12 h
• ventilation: approximately 12 cycles/hour of filtered, non-recycled air.

IN-LIFE DATES: From: 06 aug 2003 To: 11 aug 2003

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the other untreated eye served as control
Amount / concentration applied:
0.1 ml
Observation period (in vivo):
6 days (sacrifice for ethical reason)
Number of animals or in vitro replicates:
1
Details on study design:
SCORING SYSTEM: according to EU and OECD guidelines, based on grading of cornea, iris, conjunctivae and chemosis lesions.

TOOL USED TO ASSESS SCORE: For the evaluation of corneal opacification, the eyes were examined under a UV lamp after instillation of one or two drops of 0.5% sodium fluorescein solution.
Conjunctival reactions, iritis and corneal opacification were evaluated daily for each animal.
TREATMENT
As possible irritant effects were anticipated, the test item was administered to a single animal in the first instance. Since the test item showed severe irritant properties on this first animal, the study was considered complete and the test item was not evaluated on other animals.
A single dose of 0.1 mL of the undiluted test item was instilled into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for about one second to avoid any loss of test item. The right eye, which remained untreated, served as control.
Both eyes of the treated animal were rinsed approximately 24 and 48 hours after instillation of the test item for 30 seconds, with a volume and velocity of flow of a sterile isotonic saline solution (0.9% NaCl) which did not cause injury to the eyes.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean scores over 24, 48 and 72h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
on day 6
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean scores over 24, 48 and 72h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks:
on day 6
Remarks on result:
other: whitish purulent discharge
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean scores over 24, 48 and 72h
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks:
on day 6
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean scores over 24, 48 and 72h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
on day 6

Any other information on results incl. tables

Results:

Rabbit n°

 

24 hours

48 hours

72 hours

Day 6

Mean (24, 48 and 72 hours)

25

Chemosis

4

4

4

4

4

Redness (conjunctivae)

3

3

3

3

3

Iris

1

1

1

1

1

Corneal opacity

4

4

4

4

4

 

Applicant's summary and conclusion

Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Guetol is Highly irritating based on results on this test.
In EU GHS system (CLP 1272/2008) it should be classified Eye irr Cat. 1 "Causes serious eye damages".
Executive summary:

In a study (CIT, 2003), the potential of the test item Guetol to induce ocular irritation was evaluated in one rabbit according to OECD 405 guideline.

A single dose of 0.1 mL of the undiluted test item was instilled into the left conjunctival sac.

The right eye was not treated and served as control.

The eyes were not rinsed after administration of the test item, but were rinsed on days 2 and 3,

for 30 seconds, using sterile isotonic saline solution (0.9% NaCl).

Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until day 6 (sacrifice).

The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated.

Severe conjunctival reactions (severe chemosis, moderate redness of the conjunctiva and whitish purulent discharge) were observed from day1. Aslight iritis and a slight corneal opacity were also noted from day 2.

Therefore, as severe ocular reactions were observed from day 1 and as poor clinical conditions were noted from day 3 up to day 6, the animal was killed on day 6 for ethical reasons.

Mean scores calculated for the animal over 24, 48 and 72 hours were 4.0 for chemosis, 3.0 for redness of the conjunctiva, 1.0 for iris lesions and 2.0 for corneal opacity.

 

Based on these results, the test item Guetol is considered as severely irritant when administered by ocular route to rabbits, warranting classification as Eye irr Cat. 1 "Causes serious eye damages", according to EU GHS (CLP 1272/2008).