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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Remarks:
RCC Ltd, CH-4452 Itingen, Switzerland

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): FAT 40821/A
- Purity: Approx. 81%
- Lot/batch No.: TVR1
- Expiration date: 1 February 2010
- Stability of test item: Stable under storage conditions
- Storage condition: At room temperature (range of 20 ± 5°C), light and moisture (desiccator) protected.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France, BP 0109, F-69592 L'Arbresle
- Age at treatment: 11-12 weeks (male), 10-12 weeks (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 74/04, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 2/05) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
17 days
Observation period (in vivo):
up to 17 days
Number of animals or in vitro replicates:
1 male, 2 females
Details on study design:
TREATMENT:
The eyes of the animals were examined one day prior to test item administration. Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, 0.1 g of FAT 40821/A was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of test item. The right eye remained untreated and served as the reference control. The treated eyes were not rinsed after instillation.

OBSERVATIONS:
Viability/Mortality: Daily from acclimatization of the animals to the termination of test.
Clinical signs: Daily from acclimatization of the animals to the termination of test.
Body weights: At start of acclimatization, on the day of application and at termination of observation.

SCORING SYSTEM:
The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 2004/73/EC, April 29, 2004 at approximately 1, 24, 48 and 72 hours, as well as 7, 10, 14, and 17 days after instillation. Additionally, ocular discharge, reddening of the sclerea and staining of conjunctivae, sclerea and cornea by the test item was assessed.

TOOL USED TO ASSESS SCORE:
Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, CH-4153 Reinach/Switzerland).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1
Score:
0.33
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours and 7, 10, 14, 17 days
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours and 7, 10, 14, 17 days
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 hour
Score:
2
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 hours
Score:
1.33
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48 and 72 hours
Score:
1
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 7, 10, 14, 17 days
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 hour
Score:
1.67
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 hours
Score:
0.33
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48, 72 hours and 7, 10, 14, 17 days
Score:
0
Max. score:
4
Irritant / corrosive response data:
- Very slight corneal opacity affecting the whole area which was attributed to marked black staining caused by the test item was noted in one animal one hour after treatment. No abnormal findings were observed in the cornea of the remaining two animals and in the iris of any animal at any of the measurement intervals. Moderate reddening of the conjunctivae was noted in two animals at the 1-hour reading whereas the remaining animal was not assessable due to the staining produced by the test item and the opacity produced by the staining at the same reading time. Slight to moderate reddening of the conjunctivae was noted in all animals at the 24-hour examination and persisted as slight reddening of the comjunctivae up to the 72-hour reading. Slight to marked swelling (chemosis) of the conjunctivae with half-closed lids was observed in the three animals one hour after instillation and persisted as slight swelling in one animal until the 24-hour reading. Moderate reddening of the sclerea was present in two animals at the 1-hour reading whereas the remaining animal was not assessable due to the swelling produced by the test item. Slight to moderate reddening of the sclerea was noted in all animals at the 24-hour examination and persisted as slight reddening of the sclerea in one animal until the 48-hour reading and in the other animal up to the 72-hour reading. Slight to moderate ocular discharge was observed in all animals one hour after treatment and persisted as slight ocular discharge in one animal until the 24-hour examination. No abnormal findings were observed in the treated eye of any animal 7 days after treatment.
- No corrosion of the cornea was observed at any of the reading times.
Other effects:
- Slight to marked black staining produced by the test item was noted in all animals at the 1-hour reading and persisted as slight black staining in two animals up to test day 14. Black remnants of the test item were observed in the eye or conjunctival sac of two animals one hour after treatment.
- No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. One animal screamed after the application.
- The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is considered to be not irritating or corrosive to the rabbit eye.
Executive summary:

In a GLP compliant eye irritation study, performed according to OECD guideline 405, test substance (0.1 g) was placed in the conjunctional sac of the left eye of 3 New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours, as well as 7, 10, 14, and 17 days after test item instillation. The test substance showed a mean cornea score of 0.33 after 1 hour and 0 at the other time points (24 -72 hours, 7 -17 days). The conjunctivae score was 2 and 1.33 after 1 and 24 hours, respectively. After 48 and 72 hours, a score of 1 was observed and a score of 0 was present at the other time points (7 - 17 days). The chemosis score was 1.67 after 1 hour, 0.33 after 24 hours and 0 at the other time points (48, 72 hours and 7 - 17 days). The iris score was 0 during the whole observation period. No corrosion of the cornea was observed at any of the measuring intervals. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.