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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
January 3 to January 11, 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was performed according to test guideline in compliance with GLP with FAT 41030 a structural analogue of FAT 41045. Both substances are very similar in their chemical structure and, as demonstrated, in a number of physicochemical properties. Therefore, this study is used for read-across thus avoiding duplicate tests.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
FAT 41030/A
IUPAC Name:
FAT 41030/A
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
FAT 41'030/A

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Test system New Zealand White Rabbit, SPF
Rationale Recognized by the international guidelines as the recommended test system
Source Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne I France
Number of animals per test 3 (Animals of both sexes were used)
Age at start of treatment 12-13 weeks (male) 10-11 weeks (females)
Identification By unique cage number and corresponding ear number.
Acclimatization Under laboratory conditions after health examination. Only animals without any visual signs of iIIness were used for the study.
Allocation Male No. 13 Female Nos. 14 and 15
Room no. 1061 RCC Ltd, Füllinsdorf
Conditions Standard Laboratory Conditions
Air-conditioned with target ranges for room temperature 17-23 °C, relative humidity 30-70 % and approximately 10-15 air changes per hour. 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. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the light period.
Accommodation Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood (RCC Ud, Füllinsdorf) and haysticks for gnawing.
Diet Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 93/01) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis are archived at RCC Ud, Itingen.
Haysticks (QS no. 144/01) provided by Eberle Nafag AG, CH-9200 Gossau.
Water Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent vehicle
Amount / concentration applied:
0.1 g (per animal)
Duration of treatment / exposure:
lids were gently held together for one second and eyes were not rinsed thereafter
Observation period (in vivo):
1, 24, 48, 72 h after application
Number of animals or in vitro replicates:
3
Details on study design:
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, FAT 41'030/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 delivery of the animals to the termination of test.
Clinical signs Daily from delivery of the animals to the termination of test.
Body weights At start of acclimatization, on the day of application and at termination of observation.
NECROPSY
All rabbits were sacrificed by an intravenous injection of NARCOREN (Rhöne Merieux GmbH, D-88471 Laupheim) into the ear vein at a dose of at least 1 ml/kg body weight (equivalent to 160 mg sodium pentobarbitone/kg body weight) and discarded.
No necropsy was performed on the animals sacrificed at termination of observation.
IRRITATION SCORES
The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours after application. When present, corrosion and/or staining of sclera and cornea by the test item were recorded and reported. Eye examinations were made with a Varta Cliptrix diagnostic-Iamp (A. Riegger, Basel 1 Switzerland).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 48 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 3 days
Remarks on result:
other: one animal could not be scored due to staining
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
Application of the test item to healthy rabbit conjunctivae resulted in a primary eye irritation score of 0.33.
The eye reactions (mean values from 24 to 72 hours) consisted of grade 0.00 corneal opacity, grade 0.00 iris lesions, grade 0.33 redness of the conjunctivae and grade 0.00 chemosis of the conjunctivae.
No abnormal findings were observed in the cornea or iris of any animal at any of the measuring intervals.
Slight reddening was, however, subsequently observed in one animal 24 hours after treatment. Slight reddening of the conjunctivae was similarly observed in one animal from 1 to 48 hours after treatment and in the remaining animal at the 1-hour reading only .
Slight swelling or obvious swelling with partial eversion of lids was evident in all animals 1 hour after treatment.
A slight watery discharge was present in all animals at the 1-hour reading.
Assessment of the sclera was also prevented in two animals at the 1-hour reading due to staining. Slight reddening of the sclera was, however, observed in all animals during the observation period.
No abnormal findings were observed in the treated eye of any animal 72 hours after treatment, the end of the observation period for all animals.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
A light to marked red staining was observed in_ the treated eye of all animals 1 hour after treatment. A light red staining continued to be observed in one animal up to the 24-hour reading and in the other two animals up to the 48-hour reading. Red remnants of the test item were evident in all animals at the 1-hour reading and persisted in one animal up to the 24-hour reading and in another animal up to the 48-hour reading.
No corrosion of the cornea was observed at any of the reading times.
Animal number 13 showed a slight body weight loss (3%) during the acclimatization and observation period. The reason for this weight loss could not be established due to the short duration of the study. The body weights of all other rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results given in this study, test item is considered to be slightly irritation to the rabbit's eyes but not subject to classification.
Executive summary:

The primary eye irritation study was conducted to assess the possible irritation potential by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed 1, 24, 48 and 72 hours after test item application. The primary eye irritation score was calculated by totaling the mean cumulative scores at 24, 48 and 72 hours and then dividing the resulting total by the number of data points. The primary eye irritation score was 0.33 (max. 13). The eye reactions (mean values from 24 to 72 hours) consisted of grade 0.00 corneal opacity, grade 0.00 iris lesions, grade 0.33 redness of the conjunctivae and grade 0.00 chemosis of the conjunctivae.

The instillation of FAT 41030/ A into the eye resulted in mild, early-onset and transient ocular changes such as slight watery discharge, swelling and reddening of the conjunctivae and sclerae. These effects were reversible and were no longer evident 48 hours after treatment. The test item did, however, cause a red staining in the treated eye which was present up to the 48-hour reading. No abnormal findings were observed in the cornea or iris of any animal at any reading. No corrosion was observed at any of the measuring intervals. Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

Based on the results given in this study, test item is considered to be not irritating to the rabbit's eyes.