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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
24th April 2002
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
Test material form:
solid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome, Quartier Labaste, F40260 Linxe
- Age at study initiation: 11 or 18 weeks old
- Weight at study initiation: 2.21 to 3.63 kg
- Housing: Individual box
- Diet (e.g. ad libitum): SDS – C15 provided ad libitum
- Water (e.g. ad libitum): Tap water from public distribution system provided ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): Approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light : 12 hours dark

IN-LIFE DATES: Not reported

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 g per eye of test animal
Duration of treatment / exposure:
72 hours for two animals, 4 days for one animal
Observation period (in vivo):
72 hours for two animals, 4 days for one animal
Number of animals or in vitro replicates:
3
Details on study design:
TEST ANIMALS
- Source: Elevage de Gérome, Quartier Labaste, F40260 Linxe
- Age at study initiation: 11 or 18 weeks old
- Weight at study initiation: 2.21 to 3.63 kg
- Housing: Individual box
- Diet (e.g. ad libitum): SDS – C15 provided ad libitum
- Water (e.g. ad libitum): Tap water from public distribution system provided ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): Approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light : 12 hours dark

IN-LIFE DATES: Not reported

Results and discussion

In vitro

Resultsopen allclose all
Irritation parameter:
in vitro irritation score
Remarks:
1 hour
Run / experiment:
Animal # A9776
Value:
6
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
24 hours
Run / experiment:
Animal # A9776
Value:
2
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
48 hours
Run / experiment:
Animal # A9776
Value:
2
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
72 hours
Run / experiment:
Animal # A9776
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
1 hour
Run / experiment:
Animal # A9833
Value:
15
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
24 hours
Run / experiment:
Animal # A9833
Value:
6
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
48 hours
Run / experiment:
Animal # A9833
Value:
4
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
72 hours
Run / experiment:
Animal # A9833
Value:
2
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
Day 4
Run / experiment:
Animal # A9833
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
1 hour
Run / experiment:
Animal # A9834
Value:
16
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
24 hours
Run / experiment:
Animal # A9834
Value:
4
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
48 hours
Run / experiment:
Animal # A9834
Value:
2
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Irritation parameter:
in vitro irritation score
Remarks:
72 hours
Run / experiment:
Animal # A9834
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
not specified
Positive controls validity:
not applicable
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: No clinical signs related to the administration of the test item were observed. The ocular reactions observed during the study were slight to moderate and totally reversible in three animals:
- at the conjunctivae level; a slight to moderate redness noted 1 hour after test item instillation and totally reversible between day 3 and day 4, associated with a slight to moderate chemosis, noted 1 hour after the test item instillation and totally reversible between day 1 and 3.
- at the iris level; a congestion noted 1 hour after the test item instillation in only one animal.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: One eye left untreated as negative control; negative control results were not reported.
- Acceptance criteria met for positive control: Not applicable
- Range of historical values if different from the ones specified in the test guideline: Not applicable

Any other information on results incl. tables

Table 1: Individual and mean scores for conjunctivae, iris and cornea

 Animal #

 Time after Treatment

 Conjunctivae

 Iris

 Cornea

 Chemosis (A)

 Redness (C)

 Lesion (D)

 Opacity (E)

 A9776

 24 hours

 0

 1

 0

 0

 48 hours

 0  1  0  0
 72 hours  0  0  0  0

 Total

 0

 2

 0

 0

 Mean

 0.0

 0.7

 0.0

 0.0

 A9833

 24 hours

 1

 2

 0

 0

 48 hours

 1

 1

 0

 0

 72 hours

 0

 1

 0

 0

 Total

 2

 4

 0

 0

 Mean

 0.7

 1.3

 0.0

 0.0

 A9834

 24 hours

 1

 1

 0

 0

 48 hours

 0

 1

 0

 0

 72 hours

 0

 0

 0

 0

 Total

 1

 2

 0

 0

 Mean

 0.3

 0.7

 0.0

 0.0

 Classification in accordance with the European Regulation

 According to the calculated means, the item must not be classified

 Classification in accordance with GHS regulation

 According to the calculated means, the item must not be classified

Table 2: Determination of ocular irritation indicies

 Observation Time

 Total Individual Data

 Total Score

 Average Irritation Index

 Animal #

 Weight (kg)

 Animal #

 Weight (kg)

 Animal #

 Weight (kg)

 A9776

 Start: 3.51

 A9833

 Start: 2.21

 A9834

 Start: 2.32

 End: 3.63

 End: 2.31

 End: 2.44

 1 Hour (D0)

 6

 15

 16

 37

 12.3

 24 Hours (D1)

 2

 6

 4

 12

 4.0

 48 Hours (D2)

 2

 4

 2

 8

 2.7

 72 Hours (D3)

 0

 2

 0

 2

 0.7

 Day 4 (D4)

 0

 0

 0.0

 Maximum Ocular Irritation Index (Max. O.I.)

 12.3

 Classification according to the classification established in the Journal Officiel de la Republique Francaise dated July 10th, 1992

 Slightly irritant

Table 3: Total and individual scores of ocular irritation for Animal A9776

Observation Time

 Conjunctivae

 Iris

 Cornea

 Individual irritation index

 A

 B

 C

 (A+B+C)*2

 D

 D*5

 E

 F

 E*F*5

 

 

 

 X =

 

 Y =

 

 

 Z =

 X+Y+Z =

 1 Hour (D0)

 1

 1

 1

 6

 0

 0

 0

 0

 0

 6

 24 Hours (D1)

 0

 0

 1

 2

 0

 0

 0

 0

 0

 2

 48 Hours (D2)

 0

 0

 1

 2

 0

 0

 0

 0

 0

 2

 72 Hours (D3)

 0

 0

 0

 0

 0

 0

 0

 0

 0

 0

Table 4: Total and individual scores of ocular irritation for Animal A9833

Observation Time

 Conjunctivae

 Iris

 Cornea

 Individual irritation index

 A

 B

 C

 (A+B+C)*2

 D

 D*5

 E

 F

 E*F*5

 

 

 

 X =

 

 Y =

 

 

 Z =

 X+Y+Z =

 1 Hour (D0)

 2

 1

 2

 10

 1

 5

 0

 0

 0

 15

 24 Hours (D1)

 1

 0

 2

 6

 0

 0

 0

 0

 0

 6

 48 Hours (D2)

 1

 0

 1

 4

 0

 0

 0

 0

 0

 4

 72 Hours (D3)

 0

 0

 1

 2

 0

 0

 0

 0

 0

 2

 Day 4 (D4)  0  0  0  0  0  0  0  0  0  0

Table 5: Total and individual scores of ocular irritation for Animal A9834

Observation Time

 Conjunctivae

 Iris

 Cornea

 Individual irritation index

 A

 B

 C

 (A+B+C)*2

 D

 D*5

 E

 F

 E*F*5

 

 

 

 X =

 

 Y =

 

 

 Z =

 X+Y+Z =

 1 Hour (D0)

 3

 3

 2

 16

 0

 0

 0

 0

 0

 16

 24 Hours (D1)

 1

 0

 1

 4

 0

 0

 0

 0

 0

 4

 48 Hours (D2)

 0

 0

 1

 2

 0

 0

 0

 0

 0

 2

 72 Hours (D3)

 0

 0

 0

 0

 0

 0

 0

 0

 0

 0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The eye irritation potential of the test item was determined in a guideline study with New Zealand White Rabbit. The ocular reactions observed during the study were slight to moderate and totally reversible in all three animals. The results of the eye irritation study were interpreted according to the European directives 2001/59/E.C and 99/45/E.C. and in accordance with the Globally Harmonised System (Regulation (EC) No 1272/2008) and the test item must not be classified for eye irritation.
Executive summary:

The eye irritation potential of the test item was investigated in an OECD 405 and EC method B.5 guideline study with three albino white rabbits. The test item was grinded and then 0.1 g was applied to one eye of the test animal, with the other eye left untreated as a control. Observations were made after 1 hour, and then after 24, 48 and 72 hours using an opthalmoscope. The eye irritation was evaluated using a scoring system based on chemosis, discharge, redness, iris condition, degree of opacity of the cornea and extent of opacity of the cornea at each observation interval and the total and average irritation index score were calculated. The results of the eye irritation study were interpreted according to the European directives 2001/59/E.C and 99/45/E.C. and in accordance with the Globally Harmonised System (Regulation (EC) No 1272/2008.

The ocular reactions observed during the study were slight to moderate and totally reversible in all three animals. The results of the eye irritation study were interpreted according to the European directives and in accordance with the Globally Harmonised System and the test item must not be classified for eye irritation.

This study is a GLP compliant guideline experimental study, acceptable without restriction for assessment of this endpoint.