Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 1999 to July 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name "DIISOPROPYLSUCCINAT".
Chemical name Succinic acid diisopropyl ester.
Trade name DIPS.
CAS No. 924-88-9.
Batch No. EMBS 302.
Purity At least 99 %.
Density 0.9847.
Kp 247 °C.
Solubility in water Insoluble.
Storage In the refrigerator, in the dark.
Date of expiry June 1999.

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: J. Schitkovits, A-2620 Natschbach
Number and sex: 3 females
Body weight (at the start and at the termination of the test):
Animal No. 51: 2.7 kg and 2.7 kg.
Animal No. 52: 2.8 kg and 2.9 kg.
Animal No. 53: 2.7 kg and 2.8 kg.

Hygiene : Optimal hygienic conditions.
Room number: EH1-17.
Room temperature: Average of 20 °C.
Relative humidity: Average of 55 %.
Air exchange: 12 per hour.
Light: Artificial light from 6 a.m. to 6 p.m.
Cages: Individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 cm x 59 cm x 35 cm.
Feed: Altromin 2023 diet for rabbits, ad libitum. Random samples of the feed are analysed for contaminants by Altromin, D-32791 Lage.
Water: Tap water from an automatic watering system, ad libitum.
Identification: Labelling with a felt-tipped pen in an auricle.
Acclimatization: 10 days (animal No. 51) and 16 days (animals No. 52 and No. 53).

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL per animal
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
3
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.
Firstly, the test substance was given to one animal. As there was no evidence for a serious damage to the eye of this animal noted until 72 h p.a., the test substance was administered to the other two animals too.

Both eyes of the animals were examined within 24 hours before the instillation and approximately 1, 24, 48 and 72 hours p.a.
No 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:
cornea opacity score
Basis:
mean
Remarks:
all animals
Time point:
other: 1, 24, 48, 27 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
all animals
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 h
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Irritant / corrosive response data:
All eyes, treated with the test substance ("test eyes") were normal before the instillation.
All untreated eyes ("control eyes") were normal at any observation time.
Test eyes:
Cornea and Iris: Only scores of "0", i.e. normal, were noted in all animals at all examination terms.
Conjunctivae, redness: All animals were affected 1 h or 24 h p.a., with a score of "1" or "2". No changes were observed later on.
Conjunctivae, chemosis: A slight swelling with a score of "1" was observed in 1/3 animals 1 h p.a. No lesions were seen at the other animals and the other observation terms.
Other effects:
None

Any other information on results incl. tables

 

 

Mean Scores for Animal No.:

 

51

52

53

Cornea:

0.0

0.0

0.0

Iris:

0.0

0.0

0.0

Conjunctivae, redness:

0.3

0.0

0.0

Conjunctivae, chemosis:

0.0

0.0

0.0

Individual data

Examination of cornea and iris. Individual data and means.  

Time after
instillation
(p.a.)

Cornea

animal No.

Iris

animal No.

 

51

52

53

51

52

53

1 h

0

0

0

0

0

0

24 h

0

0

0

0

0

0

48 h

0

0

0

0

0

0

72 h

0

0

0

0

0

0

mean (24-72 h)

0.0

0.0

0.0

0.0

0.0

0.0

Examination of conjunctivae. Individual data and means.

Time after
instillation
(p.a.)

                                           Conjunctivae

                    Redness                                           Chemosis

                   animal No.                                          animal No.

 

51

52

53

51

52

53

1 h

0

1

2

0

0

1

24 h

1

0

0

0

0

0

48 h

0

0

0

0

0

0

72 h

0

0

0

0

0

0

mean (24-72 h)

0.3

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:
The test substance caused slight transient ocular irritation. 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.
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 conformance with the OECD-Guideline 405 and the Directive 92/69/EEC, method B.5.

Administration of the test substance

0.1 ml of "DIISOPROPYLSUCCINAT" was instilled into the conjunctival sac of one eye of each of 3 rabbits.

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 p.a.

Results

General signs

No other than ocular alterations were noted.

Eye examination

·     Corneae and irises were not affected.

·     Conjunctivae: Some injected blood vessels and diffuse crimson colour were observed in all animals 1 h or 24 h p.a. A slight swelling was observed in 1/3 animals 1 h p.a.
No lesions were observed at the other examination terms.

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.:

 

51

52

53

Cornea:

0.0

0.0

0.0

Iris:

0.0

0.0

0.0

Conjunctivae, redness:

0.3

0.0

0.0

Conjunctivae, chemosis:

0.0

0.0

0.0

 

Ocular lesions were reversible in all animals within 48 hours p.a.

 

The test substance "DIISOPROPYLSUCCINAT" is therefore only slightly irritating to the eyes. 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.