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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:
1990-08-28 to 1990-09-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and OECD guideline study with detailed descriptions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 24.2.1987
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Weight at study initiation: The animals were weighted immediately before application of the test substance.
- Housing: The rabbits were individually housed in stainless steel cages with flat rod bases or plastic cages with performated bases, under standardized conventional conditions.
- Identification of animals: The rabbits were identified by individual ear marks (tattoos) and cage cards.
- Nutrition: Standard diet "Ssniff K 4", approx. 100-120 g per animal/day, once per day in the morning.
- Water: tap water, ad libitum.
- Other: healthy anilmals. The health of the animals was routinely examined for the main specific pathogens by the breeder. No vaccinations or treatment with antibiotics were performed prior to receipt of the animals or during the acclimatization phase or study period. If females were used they were nulliparous and nonpregnant.
- State of health: After the acclimatization phase, the animals were examined one day prior to the start of the study to establish that they were biologically normal. Only animals not exhibiting any alterations to skin or eyes were used.
- Acclimatization: at least 14 days
- Animal housing conditions: All the animals in this study were kept in one room. For capacity reasons rabbits treated with other test substances were also housed in the same room. Adequate separation, slear cage and individual marks, as well as appropriate organization of working procedures ensured that the test animals were not mixed up.
- Randomization: Each rabbit was randomly assigned to the respective treatment groups. Randomization was performed by means of a random number generator with varying starting conditions, using an Apple 2e, Fachbereich Toxikologie.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3 °C
- Relative Humidity: ca. 50 %
- Air changes: ca. 10 times per hour
- Photoperiod: 12 hours artificial illumination from 6 to 18 hrs CET

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The other untreated eye served as control.
Amount / concentration applied:
100 µL
Duration of treatment / exposure:
Single treatment for 24 h
Observation period (in vivo):
1 h, 24 h, 48 h, 72 h, 7 d
Number of animals or in vitro replicates:
three animals
Details on study design:
PROCEDURE:
After gently pulling the lower lid away from the eyeball the test substance was instilled into the conjunctical sac of one eye of each of three rabbits. The lids were then gently held together for about 1 second in order to limit loss of the material.

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing with saline
- Time after start of exposure: 24 h after instillation

CLINICAL OBSERVATION AND SCORING SYSTEM:
Eye irritation was scored and recorded at the times after administration. The signs of cornea (opacity and area affected), iris (hyperaemia, reaction to light), conjuctivae - i.e. conjuctiva of bulbus, lids, and nictitating mambrane - (erythema, chemosis), and discharge were resorded as described by Draize, and the aqueous humour (opacity) as described by McDonald and Shadduck. In addition any serious lesions or toxic effects other than ocular ones were recorded. The examinations of cornea , iris and aqueaous humour were faciliated uasing optical instruments (e.g. hand slit-lmap). To define epithelial damage, one drop of a 1% fluorescin solution was applied to the corneal surface 24 h after administration of the test substance; where positive effects were recorded this was repeated at the later observation times. The eye was then rinsed with saline to remove excess and nonabsorbed fluorescein. Evaluation was performed by ultrviolet illumination (area) in a darkened room and diffuse white illumination (intensity).

EVALUATION OF RESULTS:
Only effects persisting for one than 24 hours were included on the evaluation. The irritation indices/mean iritation indices were calculated for cornea (degree of opacity), iris, erythema and swelling (chemosis) of the conjunctivae. Where three animals were used, interpretation was based on the individual indices obtained form the two most sensitive animals. Where there were delayed reactions, or where no irritation indices could be calculated (e.g. coloration by the test substance) other interpretation criteria were applied.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: regarding opacity and area
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: regarding opacity and area
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: regarding opacity and area
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: regarding redness and swelling
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: regarding redness and swelling
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: regarding redness and swelling
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24/48/72 h
Score:
0
Max. score:
2

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The results indicate that the test substance does not have a significant irritation potential on the eye. Thus, the test substance can be regarded as non irritating to the eyes.
Executive summary:

The irritant/corrosive potential of the test substance was studied on the eye of the rabbit in accordance with OECD guideline 405. Whilst considering OECD Interpretation Guides results were interpreted in conjunction with the nature, intensity and reversibility of responses observed. The irritation was scored according to Draize after 1 h, 24 h, 48 h, 72 h and 7 d. All three animals showed irritation indices of 0 for both cornea, iris conjuctivae and epithelial defects. Irritation indices for aqueous humour and discharge were 2 and 3, respectively after 1 hour. But these signs were fully reversible after 24 h. The results indicate that the test substance does not have a significant irritation potential on eye. Thus, the test substance can be regarded as non irritating to the eye.