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Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
data is from experimental reports following standard operating procedures

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Acute Eye Irritation/Corrosion Study of “Methyl 2-naphthyl ether (CAS No. – 93-04-9)” in Rabbits was performed according to OECD guideline no. 405.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report): Methyl 2-naphthyl ether
- Molecular formula :C11H10O
- Molecular weight :158.19 g/mol
- Substance type: Organic
- Physical State: Solid
Specific details on test material used for the study:
Name of test material (as cited in study report): Methyl 2-naphthyl ether
- Molecular formula :C11H10O
- Molecular weight :158.19 g/mol
- Substance type: Organic

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: LIVEON BIOLABS PVT. LTD
- Age at study initiation: 3 to 4 Months (Approximately)
- Weight at study initiation: Minimum: 1.710 kg and Maximum: 2.276 kg (Prior to Treatment)
- Housing:
Husbandry : The animals were housed individually in stainless steel cages.
Room Sanitation : The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
Cages and water bottle : All the cages and water bottles were changed minimum twice a week
- Diet (e.g. ad libitum): All animals were provided conventional laboratory rabbit diet
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum
- Acclimation period: Rabbits were acclimatised to the test conditions for a period of 7 days (Animal No.-1) and 9 days (Animal No. 2 and 3) prior to the application of the test item

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 18.90 °C Maximum: 22.70 °C
- Humidity (%): Minimum: 48.30 % Maximum: 68.30 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

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



Duration of treatment / exposure:
1 hr
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
Three female rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): normal saline
- Time after start of exposure: no data

SCORING SYSTEM: Grading of irritation lesions was carried out as per draize method

TOOL USED TO ASSESS SCORE: ophthalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animal 1,2 and 3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 21 days observation period
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
Animal 1,2 and3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 21 days observation period
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal 1,2 and 3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 21 days observation period
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animal 1, 2 and 3
Time point:
24/48/72 h
Score:
> 1 - <= 1.33
Max. score:
3
Reversibility:
fully reversible within: 21 days observation period
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Observation at 1 hour after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Some blood vessels definitely hyperaemic (injected) was seen in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was seen in all the animals.
Observation at 24 hours after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was seen in all the animals; Area of Opacity- One quarter (or less) but not zero was seen in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible was seen in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was seen in animal no. 1 and 3 whereas obvious swelling with partial eversion of lids was seen in animal no 2.
At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 40%, 50% and 40% damage in animal no. 1, 2 and 3 respectively.
Observation at 48 hours after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was seen in all the animals; Area of Opacity- One quarter (or less) but not zero was seen in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible in animal no. 3; Chemosis: Some swelling above normal (includes nictitating membranes) was seen in animal no. 1 and 2 whereas obvious swelling with partial eversion of lids in animal no. 3.
Observation at 72 hours after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was seen in all the animals; Area of Opacity- One quarter (or less) but not zero was seen in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was seen in all the animals.
Observation on day 7 after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was seen in all the animals; Area of Opacity- One quarter (or less) but not zero was seen in all the animals; Iris: Normal in all the animals; Conjunctivae- Some blood vessels definitely hyperaemic (injected) was seen in animal no.1 and diffuse, crimson color; individual vessels not easily discernible was observed in animal no. 2 and 3; Chemosis: Some swelling above normal (includes nictitating membranes) was seen in all the animals.
Observation on day 14 after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was seen in animal no. 1 and 2 whereas no ulceration or opacity was seen in animal no. 3; Area of Opacity- One quarter (or less) but not zero was seen in animals no. 1 and 2 whereas zero was seen in animal no. 3; Iris: Normal in all the animals; Conjunctivae - Some blood vessels definitely hyperaemic (injected) was seen in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was seen in all the animals.
Observation on day 21 after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Blood vessels normal in all the animals; Chemosis: No swelling (Normal) in all the animals.

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 1.00, 0.00, 2.00, 1.00; 1.00, 0.00, 2.00, 1.33, and 1.00, 0.00, 2.00, 1.33, respectively
Other effects:
Clinical Observation
No systemic toxicity was observed in treated rabbits during the experimental period.

Mortality
No mortality was observed during the observation period.

Body weight
Body weights were increased as compared to day 0 in all the three animals.



Any other information on results incl. tables

Table 1 : Individuals Animal Eye Irritation Score

Treated Dose:100 mg of test item                                                                         Sex:Female

 

Animal Number

1

Application Side

Right

Eye Reactions

*

Hour(s)

Day

1

24

48

72

7

14

21

Cornea

0

0

1

1

1

1

1

0

Area of Opacity

0

0

1

1

1

1

1

0

Iris

0

0

0

0

0

0

0

0

Conjunctiva

0

1

2

2

2

1

1

0

Chemosis

0

1

1

1

1

1

1

0

Corneal Damage (%)

40

 

 

Animal Number

2

Application Side

Right

Eye Reactions

*

Hour(s)

Day

1

24

48

72

7

14

21

Cornea

0

0

1

1

1

1

1

0

Area of Opacity

0

0

1

1

1

1

1

0

Iris

0

0

0

0

0

0

0

0

Conjunctiva

0

1

2

2

2

2

1

0

Chemosis

0

1

2

1

1

1

1

0

Corneal Damage (%)

50

 

 

Animal Numbers

3

Application Side

Right

Eye Reactions

*

Hour(s)

Day

1

24

48

72

7

14

21

Cornea

0

0

1

1

1

1

0

0

Area of Opacity

0

0

1

1

1

1

0

0

Iris

0

0

0

0

0

0

0

0

Conjunctiva

0

1

2

2

2

2

1

0

Chemosis

0

1

1

2

1

1

2

0

Corneal Damage (%)

40

Key:*= Pre-treatment eye examination.

Untreated Control                                                                                                                 Sex:Female

Animal Number

1

Application Side

Left

Eye Reactions

*

Hour(s)

Day

1

24

48

72

7

14

21

Cornea

0

0

0

0

0

0

0

0

Area of Opacity

0

0

0

0

0

0

0

0

Iris

0

0

0

0

0

0

0

0

Conjunctiva

0

0

0

0

0

0

0

0

Chemosis

0

0

0

0

0

0

0

0

Corneal Damage (%)

0

 

Animal Number

2

Application Side

Left

Eye Reactions

*

Hour(s)

Day

1

24

48

72

7

14

21

Cornea

0

0

0

0

0

0

0

0

Area of Opacity

0

0

0

0

0

0

0

0

Iris

0

0

0

0

0

0

0

0

Conjunctiva

0

0

0

0

0

0

0

0

Chemosis

0

0

0

0

0

0

0

0

Corneal Damage (%)

0

 

Animal Number

3

Application Side

Left

Eye Reactions

*

Hour(s)

Day

1

24

48

72

7

14

21

Cornea

0

0

0

0

0

0

0

0

Area of Opacity

0

0

0

0

0

0

0

0

Iris

0

0

0

0

0

0

0

0

Conjunctiva

0

0

0

0

0

0

0

0

Chemosis

0

0

0

0

0

0

0

0

Corneal Damage (%)

0

Key:*= Pre-treatment eye examination.

Table 1 Continued…

 

Eye Irritation Scores - Mean Values after 24, 48, 72 Hours (Treated eye)

            Animal No.

 Eye Reaction

1

2

3

Corneal Opacity

1.00

1.00

1.00

Iris

0.00

0.00

0.00

Conjunctiva

2.00

2.00

2.00

Chemosis

1.00

1.33

1.33

Formula :

 

Mean Eye Irritation Score =

                          

Sum of the Individual Animal Score for eye reactionat24, 48 and 72 hours

Number of the Observations (3)

Table 2 : Individual AnimalClinicalSigns

 

Sex:Female

Animal No.

Days (Post application observation)

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

Key:1 = Normal

Table 3: Individual Animal Body Weight

Sex :Female

Animal No.

Animal Body Weight (kg)

Prior to application

At termination

1

1.728

2.142

2

2.276

2.616

3

1.710

1.894

Key:kg = Kilogram

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 1.00, 0.00, 2.00, 1.00; 1.00, 0.00, 2.00, 1.33, and 1.00, 0.00, 2.00, 1.33, respectively. The effects observed in all the animals were fully reversible within an observation period of 21 days.
Hence under the experimental test conditions, the test chemical was “An Eye Irritant (Irritating to Eyes)” of New Zealand White Female rabbit eyes.
Executive summary:

Acute Eye Irritation/Corrosion Study of the test chemical was performed as per OECD guideline no. 405.

Rabbits free from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment. One eye of each rabbit served as control and other as treated. Control eye was left untreated whereas; 0.1 gof test itemwas instilled in the other (treated) eye of each rabbit.The eye was observed at 1, 24, 48, 72 hour, day 7, day 14 and day 21 for all the three animals post test item instillation.Ophthalmoscope was used for scoring of eye lesions. In the initial test,100 mg of test itemwas instilled into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions; hence a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 100 mgof test itemwas instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control. All the animals were observed till day 21 post test item instillation. Untreated eye of all the three rabbits were normal throughout the experimental period.

 The following grading scores were observed in treated eye of tested rabbits.

Observation at 1 hour after instillation of test item revealed: Cornea-No ulceration or opacity was seen in all the animals;Area of Opacity-Zero inall the animals;Iris:Normal in all the animals;Conjunctivae - Some blood vessels definitely hyperaemic (injected) was seen in all the animals;Chemosis:Some swelling above normal (includes nictitating membranes) was seen in all the animals.

Observation at 24 hours after instillation of test item revealed: Cornea-Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was seen in all the animals;Area of Opacity- One quarter (or less) but not zerowas seen in all the animals;Iris:Normal in all the animals;Conjunctivae -Diffuse, crimson color; individual vessels not easily discernible was seen in all the animals;Chemosis:Some swelling above normal (includes nictitating membranes) was seen in animal no. 1 and 3 whereas obvious swelling with partial eversion of lids was seen in animal no 2.

At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 40%, 50% and 40% damage in animal no. 1, 2 and 3 respectively.Observation at 48 hours after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was seen in all the animals;Area of Opacity-One quarter (or less) but not zero was seen inall the animals;Iris:Normal in all the animals;Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible in animal no. 3;Chemosis:Some swelling above normal (includes nictitating membranes) was seen in animal no. 1 and 2 whereas obvious swelling with partial eversion of lids in animal no. 3.Observation at 72 hours after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was seen in all the animals;Area of Opacity-One quarter (or less) but not zero was seen inall the animals;Iris:Normal in all the animals;Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible in all the animals;Chemosis:Some swelling above normal (includes nictitating membranes) was seen in all the animals. Observation on day 7 after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was seen in all the animals;Area of Opacity-One quarter (or less) but not zero was seen inall the animals;Iris:Normal in all the animals;Conjunctivae-Some blood vessels definitely hyperaemic (injected) was seen in animal no.1 and diffuse, crimson color; individual vessels not easily discernible was observed in animal no. 2 and 3;Chemosis:Some swelling above normal (includes nictitating membranes) was seen in all the animals.Observation on day 14 after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was seen in animal no. 1 and 2 whereas no ulceration or opacity was seen in animal no. 3;Area of Opacity-One quarter (or less) but not zero was seen in animals no. 1 and 2 whereas zero was seen inanimal no. 3;Iris:Normal in all the animals;Conjunctivae -Some blood vessels definitely hyperaemic (injected) was seen in all the animals;Chemosis:Some swelling above normal (includes nictitating membranes) was seen in all the animals. Observation on day 21 after instillation of test item revealed: Cornea-No ulceration or opacity in all the animals;Area of Opacity-Zero in all the animals;Iris:Normal in all the animals;Conjunctivae -Blood vessels normal in all the animals;Chemosis:No swelling (Normal) in all the animals.

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 1.00, 0.00, 2.00, 1.00; 1.00, 0.00, 2.00, 1.33, and 1.00, 0.00, 2.00, 1.33, respectively. The effects observed in all the animals were fully reversible within an observation period of 21 days.  

Hence under the experimental test conditions, the test chemical was “An Eye Irritant (Irritating to Eyes)” of New Zealand White Female rabbit eyes.