Registration Dossier

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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.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:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Remarks:
RCC Ltd., Toxicology, Wölferstrasse 4, CH-4414 Füllinsdorf / Switzerland

Test material

Constituent 1
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): FAT 40'812/A
- Purity: Approx. 75%
- Lot/batch No.: WP 3/03
- Expiration date: 23 April 2010
- Stability: Stable under storage conditions
- Storage conditions: At room temperature (range of 20 ± 3 °C), away from direct sunlight

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne / France
- Age at treatment: 10 weeks (male), 11 weeks (females)
- Bodyweight at treatment: 2227 - 2574 g
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd., Füllinsdorf) and haysticks 4646 (batch no. 0301, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 28/03) 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:
21 days
Observation period (in vivo):
up to 21 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 40'812/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 92/96/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours, as well as 7, 10, 14, 17, and 21 days after instillation. When present, corrosion and/or staining of conjunctivae, sclerae and cornea by the test item were recorded and reported.

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, 24, 48, 72 hours and 7, 10, 14, 17, 21 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, 21 days
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1, 24 hours
Score:
1
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48 hours
Score:
0.67
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 hours
Score:
0.33
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 7, 10, 14, 17, 21 days
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 hour
Score:
2
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 hours
Score:
0.67
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48, 72 hours and 7, 10, 14, 17, 21 daysdays
Score:
0
Max. score:
4
Irritant / corrosive response data:
- No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals. Slight reddening of the conjunctivae was observed in all animalsat the 1- and 24 hour reading. Slight redding was still noted in two animals at the 48-hour examination and persisted in one animal up to 72-hours after treatment. Moderate swelling of the conjunctivae (oedema) was noted in all animals at the 1-hour reading. Slight swelling of the conjunctivae was still evident in two animals 24 hours after treatment. Slight reddening of the sclerea was present in all animals at the 1-hour reading and persisted in one animal up to 24-hours after treatment. Slight to moderate discharge was noted in all animals at the 1-hour examination. One animal screamed immediately after application of the test item for a few seconds.
- No corrosion of the cornea was observed at any of the reading times.
Other effects:
- Slight red staining of the treated eyes produced by the test item was observed in all animals one hour after treatment and persisted in all animals up to the end of the observation period. Red remnants of the test item were observed in the eye or conjunctival sac of all 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:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
These effects were reversible and were no longer evident 7 days after treatment. Red staining of the treated eyes produced by the test item was observed in all animals at the 1 -hour examination and persisted up to the observation 21 days after treatment. No abnormal findings were observed in the iris of any animal at any of the examinations, no corrosion was observed at any of the measuring intervals and no clinical signs were observed.
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, 17, and 21 days after test item instillation. The instillation of the test substance into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerea, discharge and chemosis. These effects were reversible and were no longer evident 7 days after treatment. Red staining of the treated eyes produced by the test item was observed in all animals at the 1 -hour examination and persisted up to the observation 21 days after treatment. No abnormal findings were observed in the iris of any animal at any of the examinations, no corrosion was observed at any of the measuring intervals and no clinical signs were observed.