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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 19 December 2000 and 25 December 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with OECD guidelines and in compliance with GLP.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: colorless liquid
Details on test material:
Storage conditions: at room temperature and protected from light

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animals
Sex, species, strain: male New Zealand White rabbits.
Reason for this choice: species generally accepted by regulatory authorities for this type of study.
Breeder: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
Number of animals: three animals were used, as recommended by the international guidelines.
Weight: on the day of treatment, the animals had a mean body weight ± standard deviation of 2.8 ± 0.1 kg.
AccIimation: at least 5 days before the beginning of the study.
Identification: individual metal ear tag.

Environmental conditions
The conditions in the animal room were set as follows:
temperature: 20 ± 3°C
relative humidity: 30 to 70%
light/dark cycle: 12 h/12 h
ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment were verified and calibrated at regular intervals.
The animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
Each cage was equipped with a food container and a water bottle.

Food and water
During the study, the animals had free access to 112C pelleted diet (UAR, 91360 Villemoissonsur -Orge, France).
Each batch of food is analysed by the supplier for composition and contaminant levels.
Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
Bacteriological and chemical analyses of water are performed regularly by external laboratories.
These analyses include the detection of possible contaminants (pesticides, heavy metals and nitrosamines).
No contaminants were known to have been present in the diet or drinking water at levels which may be expected to have interfered with or prejudiced the outcome of the study.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye remained untreated and was used for control purposes.
Amount / concentration applied:
0.1 ml of the undiluted test substance
Duration of treatment / exposure:
Up to 1 hour
Observation period (in vivo):
Up to 5 days
Number of animals or in vitro replicates:
3
Details on study design:
TREATMENT

Selection of the animals
The day before treatment, the eyes of each animal were examined in order to use only animals without any signs of ocular lesions. Animals showing signs of ocular irritation, ocular defects or pre-existing corneal injury were not used.

Administration of the test substance
As possible irritant effects were anticipated, the test substance was administered to a single animal (No. 59) in the first instance. Since the test substance was not severely irritant on this first animal, it was then evaluated on two other animals (Nos. 71 and 72).
A single dose of 0.1 ml of the undiluted test substance 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 substance. The right eye, which remained untreated, served as control.
The eyes were not rinsed after administration of the test substance.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal: 59
Time point:
other: Score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal: 71
Time point:
other: Score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks:
No effects observed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal: 72
Time point:
other: Score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal: 59
Time point:
other: Score at 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal: 71
Time point:
other: Score at 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal: 72
Time point:
other: Score at 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: No effects observed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal: 59
Time point:
other: Score at 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal: 71
Time point:
other: Score at 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: Day 5
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal: 72
Time point:
other: Score at 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal: 59
Time point:
other: Score at 1, 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal: 71
Time point:
other: Score at 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: Day 5
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
72
Time point:
other: Score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
Slight conjunctival reactions were observed in all animals on day 1: a very slight chemosis (grade 1) and a slight redness of the conjunctiva (grade 1) were noted. These ocular reactions persisted up to day 4 in 1/3 animals.
No other ocular reactions were recorded during the study.
Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 1.0 and 0.0 for chemosis, 0.0, 1.0 and 0.0 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under our experimental conditions, the test substance Vivaldie is non-irritant when administered by ocular route to rabbits.
Executive summary:

The potential of the test substance Vivaldie to induce ocular irritation was evaluated in rabbits according to OECD ( No. 405, 24th February 1987 ) and EC (92/69/EEC, B.5, 31st July 1992 ) guidelines. As possible irritant effects were anticipated, the test substance was administered to a single male New Zealand White rabbit in the first instance. Since the test substance was not severely irritant on this first animal, it was then evaluated in two other animals. A single dose of 0.1 rnl of the undiluted test substance 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 substance. Slight conjunctival reactions (very slight chemosis and slight redness of the conjunctiva) were observed in all animals on day 1; they persisted up to day 4 in 1/3 animals.

No other ocular reactions were noted during the study. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 1.0 and 0.0 for chemosis, 0.0, 1.0 and 0.0 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity. Under the experimental conditions of this test, the test substance Vivaldie is non-irritant when administered by ocular route to rabbits.