Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 02 April 2007 and 13 April 2007.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

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 (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification: C-Y9
Description : yellow powder
Batch number : MB-1
Date received : 06 March 2007
Storage conditions: room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Three New Zealand White rabbits were supplied by an accredited supplier.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (Certified Rabbit Diet) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
A volume of 0.1 ml of the test material, which was found to weigh approximately 92 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released.

The left eye remained untreated and was used for control purposes.
Duration of treatment / exposure:
A single application of the test material was given.
Observation period (in vivo):
72 hours.
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM:
Immediately after administration of the test material, an assessment of the initial pain reaction was made.

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation Draize Scale for Scoring Ocular Irritation.

Any other ocular effects were also noted.


TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

OTHER:
Measurement of pH: The pH of the test material was determined prior to commencement of the study and found to be as follows:
Preparation - 10% w/w aqueous preparation of the test material
pH measurement immediately - 8.6
pH measurement after 10 minutes - 8.4





Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
: Animal 1
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
: Animal 2
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
: Animal 3
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
: Animal 1
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Remarks:
: Animal 2
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Remarks:
: Animal 3
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
: Animal 1
Time point:
other: Mean of 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
: Animal 2
Time point:
other: Mean of 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
: Animal 3
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
: Animal 1
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
: Animal 2
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
: Animal 3
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Individual and group mean scores for ocular irritation are given in Table 1 and Table 2.

No corneal or iridial effects were noted.

Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal to moderate conjunctival irritation noted in all treated eyes at the 24-hour observation and minimal conjunctival irritation noted in all treated eyes at the 48-hour observation.

All treated eyes appeared normal at the 72-hour observation.
Other effects:
Yellow-coloured staining of the fur was noted around all treated eyes throughout the study.

Any other information on results incl. tables

Table1               Individual Scores and Individual Total Scoresfor Ocular Irritation

Rabbit Number and Sex

66091 Male

66144 Male

66143 Male

IPR= 2

IPR = 2

IPR = 2

Time After Treatment

1

Hour

24

Hours

48

Hours

72

Hours

1

Hour

24

Hours

48

Hours

72

Hours

1

Hour

24

Hours

48

Hours

72

Hours

CORNEA

 

 

 

 

 

 

 

 

 

 

 

 

E = Degree of Opacity

0

0

0

0

0

0

0

0

0

0

0

0

F = Area of Cornea Involved

0

0

0

0

0

0

0

0

0

0

0

0

Score (E x F) x 5

0

0

0

0

0

0

0

0

0

0

0

0

IRIS

 

 

 

 

 

 

 

 

 

 

 

 

D

0

0

0

0

0

0

0

0

0

0

0

0

Score (D x 5)

0

0

0

0

0

0

0

0

0

0

0

0

CONJUNCTIVAE

 

 

 

 

 

 

 

 

 

 

 

 

A = Redness

2

2

1

0

2

2

1

0

2

1

1

0

B = Chemosis

1

1

0

0

1

1

0

0

1

1

0

0

C = Discharge

2Sf

1Sf

0Sf

0Sf

2Sf

1Sf

0Sf

0Sf

2Sf

1Sf

0Sf

0Sf

Score (A + B + C) x 2

10

8

2

0

10

8

2

0

10

6

2

0

Total Score

10

8

2

0

10

8

2

0

10

6

2

0


IPR= Initial pain reaction

Sf= Yellow-coloured staining of the fur around the treated eye

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material did not meet the criteria for classifcation as an eye irritant according to EU CLP regulations.

The test material did not meet the criteria for classification as irritant according to EU labelling regulations Commission Directive 2001/59/EC (Dangerous Substances Directive).


Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

§        OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted)

§        Method B5 Acute Toxicity (Eye Irritation) of Commission Directive 2004/73/EC

Result. 

A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 72-hour observation.

Conclusion.

The test material did not meet the criteria for classifcation as an eye irritant according to EU CLP regulations.

The test material did not meet the criteria for classification as irritant according to EU labelling regulations Commission Directive 2001/59/EC (Dangerous Substances Directive).