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 study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

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)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name "Isomaltulose Solution".
Trade name Isomaltulose Solution
Batch No. 03160483
Density 1.2 g/cm3 (20 °C)
Solubility in water unlimited.
Storage room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species and strain: Rabbits, New Zealand White.
Supplier: Charles River Deutschland GmbH, D-88353 Kisslegg.
Number and sex: 3 females.
Body weight (at the start and at the termination of the study):
Animal No. 21: 2.2 kg and 2.3 kg.
Animal No. 22: 2.5 kg and 2.6 kg.
Animal No. 23: 2.4 kg and 2.5 kg.

Hygiene: Optimal hygienic conditions.
Room number: EI1-8.
Room temperature: Ranges from 19.29 to 21.42 °C.
Relative humidity: Ranges from 44.31 to 68.90 %.
Air exchange: 12 per hour.
Light: Artificial light from 6 a.m. to 6 p.m.
Cages: Individual caging in terulan cages, Ehret GmbH, A-3430 Tulln, 65 cm x 65 cm bottom area, 50 cm height.
Feed: Ssniff K-H maintenance diet for rabbits (item V-2333-000), ad libitum, supplied by Ssniff Spezialdiäten GmbH, 59494 Soest, Germany.
Water: Tap water from an automatic watering system, ad libitum.
Identification: Labelling with felt-tipped pen on a pinna and cage labels.
Acclimatisation: 7 days (animal No. 21) and 14 days (animal Nos. 22 and 23)

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL of the test substance was administered into the right eyes of each animal.
Duration of treatment / exposure:
The test substance was held closed for about 1 second to hold the test substance in the eye.
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
3 females
Details on study design:
0.1 ml of the test substance was administered into the conjunctival sac of the right eye by gently pulling the lower lid away from the eyeball for instillation. The eye was held closed for about one second to prevent a loss of test substance. The left eye remained untreated and served as a control. The test substance was given to one animal. As no evidence for a serious damage to the eye of this animal was found during the initial 72 hour observation, the test substance was administered to the other two animals subsequently.

Both eyes of the animals were examined within 24 hours before the instillation and approximately 1, 24, 48 and 72 hours p.a. No further examinations were performed thereafter. The scoring terms of 24, 48 and 72 h after the instillation were decisive for the interpretation of the results and the conclusion of the study. The whole eye, especially the cornea, the iris and the conjunctivae were examined, using an otoscope lamp. Eye irritation was scored and recorded using the scheme for eye lesions.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: all
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
other: all
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: all
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: all
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
All treated and untreated eyes appeared normal throughout the study.
Other effects:
None

Any other information on results incl. tables

 

Mean Scores for Animal No.:

 

21

22

23

Cornea:

0.0

0.0

0.0

Iris:

0.0

0.0

0.0

Conjunctivae, redness:

0.0

0.0

0.0

Conjunctivae, chemosis:

0.0

0.0

0.0

Individual data

 Examination of corneae, irises and conjunctivae. Individual data and means.
              

 

 

 

Conjunctivae

Time after
instillation
(p.a.)

Corneae
animal No.

Irises
animal No.

Redness
animal No.

Chemosis
animal No.

 

21

22

23

21

22

23

21

22

23

21

22

23

1 h

0

0

0

0

0

0

0

0

0

0

0

0

24 h

0

0

0

0

0

0

0

0

0

0

0

0

48 h

0

0

0

0

0

0

0

0

0

0

0

0

72 h

0

0

0

0

0

0

0

0

0

0

0

0

mean
(24-72 h)

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No symptoms of systemic toxicity were observed in the animals at any time period. No mortality occurred.
Executive summary:

The aim of this study was to investigate possible irritating or corrosive effects of the test substance following a single administration into the conjunctival sac of one eye of rabbits.

Methods

Methods and investigations were performed in accordance with the OECD-Guideline 405 and theCouncil Regulation (EC) No 440/2008,Method B.5.

Administration of the test substance

0.1 mL of"Isomaltulose Solution"was instilled into the conjunctival sac of one eye of each of 3 New Zealand White rabbits.Firstly the test substance was administered to one animal. As there was no corrosive or severe irritant effect observed, the test substance was administered to two additional animals one week later.

Investigations

·     Body weights: at the start and at the termination of the test.

·     General signs of toxicity: once daily.

·     Eye examination: 1, 24, 48 and 72 h after the administration (p.a.) of the test substance.

Results

General signs

No other than ocular alterations were noted.

Eye examination

·     Corneae and irises: Not affected at any observation point.

·     Conjunctivae: Not affected at any observation point.

 

Conclusion

The following mean scores were calculated for each animal from the individual examinations performed 24 h, 48 h and 72 h p.a.:

 

 

Mean Scores for Animal No.:

 

21

22

23

Cornea:

0.0

0.0

0.0

Iris:

0.0

0.0

0.0

Conjunctivae, redness:

0.0

0.0

0.0

Conjunctivae, chemosis:

0.0

0.0

0.0

 

Based on the mean scores calculated from the individual examinations performed 24, 48 and 72 h p.a. and referring to Commission Directive 2001/59/EC the test substance does not require classification for eye irritation.