Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 06 May 2010 and 27 May 2010.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline 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:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Department of Health of the Government of the United Kingdom

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK
- 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. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Diet: ad libitum (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK)
- Water: ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 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:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL equal to approximately 99 mg


VEHICLE
none: used as supplied
Observation period (in vivo):
Approximately 1 hour and 24, 48 and 72 hours following treatment. An additional observation was made in one treated eye on Day 7 to assess the reversibility of the ocular effects.
Number of animals or in vitro replicates:
2 animals were tested in total. (After consideration of the ocular responses produced in the first treated animal, one additional animals was treated. )

Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: eyes not washed

SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation given in Appendix 2, (from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).


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

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
69200 Male
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
69242 Male
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
69200 Male
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: No effect observed
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
69242 Male
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: No effect observed
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
69200 Male
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
69242 Male
Time point:
other: Mean 24, 48 and 72 hours
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
69200 Male
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
69242 Male
Time point:
24/48/72 h
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 during the test.
Moderate conjunctival irritation was noted in both treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24 and 48 hour observations. Minimal conjunctival irritation persisted in one treated eye at the 72-Hour observation.
One treated eye appeared normal at the 72 Hour observation and the other treated eye appeared normal at the 7 Day observation.
Other effects:
Body weight
Both animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table1               IndividualScores and Individual Total Scoresfor Ocular Irritation

Rabbit Number and Sex

69200Male

69242Male

IPR= 2

IPR = 2

Time After Treatment

1
Hour

24
Hours

48
Hours

72
Hours

7
Days

1
Hour

24
Hours

48
Hours

72
Hours

CORNEA

 

 

 

 

 

 

 

 

 

E = Degree of Opacity

0

0

0

0

0

0

0

0

0

F = Area of Cornea Involved

0

0

0

0

0

0

0

0

0

Score (E x F) x 5

0

0

0

0

0

0

0

0

0

IRIS

 

 

 

 

 

 

 

 

 

D

0

0

0

0

0

0

0

0

0

Score (D x 5)

0

0

0

0

0

0

0

0

0

CONJUNCTIVAE

 

 

 

 

 

 

 

 

 

A = Redness

2

1

1

1

0

2

1

1

0

B = Chemosis

2

1

0

0

0

2

1

0

0

C = Discharge

2

1

0

0

0

2

1

0

0

Score (A + B + C) x 2

12

6

2

2

0

12

6

2

0

Total Score

12

6

2

2

0

12

6

2

0

IPR=  Initial pain reaction (scroes 0 - 5; 2= Rabbit blinks and tries to pen eye, but refelex closes it)

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material produced a maximum group mean score of 12.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.The test material did not meet the criteria for classification as irritant according to Regulation (EC) No. 1272/2008 (EU CLP). This study is conducted according to the appropriate guidelines (EU ) and under the conditions of GLP and therefore the study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement as a key study for this endpoint. Study is sufficient for classification and labelling purposes, in accordance with Regulation (EC) No. 1272/2008 (EU CLP).
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 24 April 2002)

Method B5 Acute Toxicity (Eye Irritation) of Commission  Regulation (EC) No. 440/2008

Initial considerations.

Due to the high pH value of the test material a Rabbit Enucleated Eye Test (REET) was performed prior to thein vivo test. The results are given in Appendix 4 and indicated that the test material was unlikely to cause severe ocular irritancy.

Result. 

A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. One treated eye appeared normal at the 72-Hour observation and the other treated eye appeared normal at the 7-Day observation.

Conclusion. 

The test material produced slight and reversable conjunctivae and chemosis reactions.

The test material did not meet the criteria for classification as irritant according to Regulation (EC) No. 1272/2008 (EU CLP).