Registration Dossier

Administrative data

Description of key information

Skin irritation

The dermal irritation potential of target chemical was assessedin various in- vitro and in-vivo experimental studies which were conducted for test chemical.Based on the available key data and supporting studies,it can be concluded that the testchemical is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Irritating”.

 

Eye irritation

Acute Eye Irritation/Corrosion Study of Test chemical in Rabbits, was performed as per OECD guideline No. 405. The treated 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. 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. Hence under the experimental test conditions, Methyl 2-naphthyl ether was considered to be irritating to New Zealand White Female rabbit eyes. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2 (irritating to eyes)”.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
Data from experimental study report.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Acute Dermal Irritation/Corrosion study of Methyl 2-naphthyl ether was performed in Rabbits
GLP compliance:
yes
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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: LIVEON BIOLABS PVT LTD
- Age at study initiation: 2.5 to 3.5 Months (Approximately)
- Weight at study initiation: Minimum: 1.624 kg & Maximum: 2.100 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 ad libitum
- 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 6 days (Animal No.-1) and 8 days (Animal No.-2 and 3) prior to the application of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 20.30 °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

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg moistened with 0.5 ml distilled water


VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution):no data
- Lot/batch no. (if required): no data
- Purity: no data
Duration of treatment / exposure:
4-hour exposure period
Observation period:
72 hours
Number of animals:
Three of each sex
Details on study design:
TEST SITE
- Area of exposure: dorsal lumbar region at contralateral sites
- % coverage: approximately 6 X 6 cm
- Type of wrap if used: porous gauze dressing and non-irritating tape (Micropore 3”)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance was removed by using cotton soaked in distilled water
- Time after start of exposure: 4 hrs

SCORING SYSTEM: Grading of irritation lesions was carried out as per Draize Method
Irritation parameter:
erythema score
Basis:
mean
Remarks:
Animal 1,2,3
Time point:
other: 24, 48 and 72 hours
Score:
0 - 0.33
Max. score:
3
Reversibility:
no data
Remarks on result:
other: not irritating
Irritation parameter:
edema score
Basis:
mean
Remarks:
Animal 1,2 and 3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
3
Reversibility:
no data
Remarks on result:
other: not irritating
Irritant / corrosive response data:
Animal No. 1, showed very slight erythema (barely perceptible) and no oedema observed at 1 hour of observation. At 24, 48 and 72 hour observation no erythema and oedema was observed in animal No 1.
In Animals No. 2 and 3 at 1 hour observation post patch removal, revealed very slight erythema (barely perceptible) and no oedema. At 24 hour animal no. 2 showed no erythema and oedema whereas animal no. 3 revealed very slight erythema (barely perceptible) and no oedema. At 48 and 72 hour post patch removal, both the animals recovered to normal.
Other effects:
Clinical Observation
No systemic toxicity was observed at treated rabbits during the experimental period.

Mortality
No mortality was observed during the observation period.

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


Table 1

Skin Reaction

 

In Treated area Dose:500 mg of test item (moistened with 0.5 ml distilled water)           Sex:Male

 

Animal

No.

Test

Treated

 area*

Erythema score

Oedema score

1h

24h

48h

72h

1h

24h

48h

72h

1

Initial

Left

1

0

0

0

0

0

0

0

2

Confirmatory

Left

1

0

0

0

0

0

0

0

3

Left

1

1

0

0

0

0

0

0

 

 

In Control areaDose:0.5 ml of distilled water                                                          Sex:Male

 

Animal

No.

Test

Treated area*

Erythema score

Oedema score

1h

24h

48h

72h

1h

24h

48h

72h

1

Initial

Right

0

0

0

0

0

0

0

0

2

Confirmatory

Right

0

0

0

0

0

0

0

0

3

Right

0

0

0

0

0

0

0

0

Key: h = Hour.

Erythema                                                                                                       Oedema

0 =No erythema                                                                                           0 =No oedema

1 = Very slight erythema(barely perceptible)

Table 1 Continued…

Mean Individual Animal Score at 24, 48 and 72 hours

 

                     Animal Number                  

Observations                      

1

2

3

Erythema

0.00

0.00

0.33

Oedema

0.00

0.00

0.00

Table 2

Individual Animal BodyWeight

Sex:Male

Animal

No.

Body Weight (kg)

Prior to Dosing

At termination

1

1.624

1.718

2

2.100

2.172

3

1.846

1.922

Table 3

Individual AnimalClinicalSigns

Sex:Male

Animal

No.

Days (Post dosing Observation)

0

1

2

3

1

1

1

1

1

2

1

1

1

1

3

1

1

1

1

Key: ./. = Not Applicable. 1 = Normal.

Interpretation of results:
other: not irritating
Conclusions:
No erythema and oedema (skin irritation) were observed at the end of 72 hour observation period after patch removal. Hence, it was considered to be Methyl 2-naphthyl ether was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested
Executive summary:

Acute Dermal Irritation/corrosion Study of Methyl 2-naphthyl ether was performed as per OECD guideline No. 404.Three healthy young adult male rabbits were used for the study. The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment.A dose of 500 mgof test item (moistened with 0.5 ml distilled water) was applied to the skin,over an area of approximately 6 x 6 cm clippedof hair on one side of rabbits.The other untreated side was kept as control area and 0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test item application site was wiped with water. Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch.After 4 hours of exposure in animal no. 1,very slight erythema (barely perceptible) and no oedema observed at 1 hour of observation. At 24, 48 and 72 hours observation no erythema and oedema was observed in animal no 1.Hence the confirmatory test was conducted on additional two rabbits (No. 2 and 3)to confirm the non irritant nature of the test item. The patch was removed after 4 hours and rabbits wereobservedfor erythema and oedemaat 1, 24, 48 and 72 hours after patch removal, evaluatedand graded as per draize method. In animal no. 2 and 3 at 1 hour observation post patch removal, revealed very slight erythema (barely perceptible) and no oedema. At 24 hour animal no. 2 showed no erythema and oedema whereas animal no. 3 revealed very slight erythema (barely perceptible) and no oedema, At 48 and 72 hour post patch removal, both the animals recovered to normal. The individual mean score at 24, 48 and 72 hours for animal nos. 1, 2 and 3 were 0.00, 0.00, 0.33 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively. Hence, it was considered to be  Methyl 2-naphthyl ether was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
Data from experimental study report
Qualifier:
according to guideline
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 ” was performed in Rabbits
GLP compliance:
yes
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
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

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100mg (0.1 g)



Duration of treatment / exposure:
1 hr
Observation period (in vivo):
21 days
Duration of post- treatment incubation (in vitro):
No data available
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
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animal 1,2 and 3
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 21 days observation period
Remarks on result:
other: irritating
Irritation parameter:
iris score
Basis:
mean
Remarks:
Animal 1,2 and3
Time point:
other: 24, 48, 72
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 21 days observation period
Remarks on result:
other: Irritating
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal 1,2 and 3
Time point:
other: 24, 48, 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 21 days observation period
Remarks on result:
other: Irritating
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
Animal 1, 2 and 3
Time point:
other: 24, 48, 72 hours
Score:
1 - 1.33
Max. score:
3
Reversibility:
fully reversible within: 21 days observation period
Remarks on result:
other: Irritaing
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.



Table 1 : Individual Animal Eye Irritation Scores

 

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

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
All the three animals were fully reversible within an observation period of 21 days. Hence under the experimental test conditions,Methyl 2-naphthyl ether was considered to be irritating to New Zealand White Female rabbit eyes .
Executive summary:

Acute Eye Irritation/Corrosion Study of Methyl 2-naphthyl ether 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. 0.1 g of test item was 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 item was 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 mg of test item was 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.

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, respectivelyHence under the experimental test conditions,Methyl 2-naphthyl ether was considered to be irritating to New Zealand White Female rabbit eyes .

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

Various studieshave been investigated for the test chemical to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in-vitro and in-vivo experiments conducted for target chemical in rabbits and human. The predicted data usingDanish QSAR databasethe has also been compared with the experimental data and summarized as below;

 

Acute Dermal Irritation/corrosion Study of test chemical was performed as per OECD guideline No. 404 using three healthy young adult male rabbits were used for the study. The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment. A dose of 500 mg of test item (moistened with 0.5 ml distilled water) was applied to the skin, over an area of approximately 6 x 6 cm clipped of hair on one side of rabbits. The other untreated side was kept as control area and 0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test item application site was wiped with water. Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. After 4 hours of exposure in animal no. 1,very slight erythema (barely perceptible) and no oedema observed at 1 hour of observation. At 24, 48 and 72 hours observation no erythema and oedema was observed in animal no 1. Hence the confirmatory test was conducted on additional two rabbits (No. 2 and 3)to confirm the non-irritant nature of the test item. The patch was removed after 4 hours and rabbits were observed for erythema and oedemaat 1, 24, 48 and 72 hours after patch removal, evaluated and graded as per draize method. In animal no. 2 and 3 at 1 hour observation post patch removal, revealed very slight erythema (barely perceptible) and no oedema. At 24 hour animal no. 2 showed no erythema and oedema whereas animal no. 3 revealed very slight erythema (barely perceptible) and no oedema, At 48 and 72 hour post patch removal, both the animals recovered to normal. The individual mean score at 24, 48 and 72 hours for animal nos. 1, 2 and 3 were 0.00, 0.00, 0.33 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively. Hence, it was considered to be Methyl 2-naphthyl ether was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested.

 

The above in-vivo study was supported by the in-vitro test conducted for test chemical according to the OECD 439 test guideline. The MatTek EpiDerm™ model was used to assess the potential dermal irritation of the test article by determining the viability of the tissues following exposure to the test article via MTT. Tissues were exposed to the test article and controls for ~one hour, followed by a 42 hour post-exposure recovery period. The viability of each tissue was determined by MTT assay.  The MTT data show the assay quality controls were met and passed the acceptance of criteria. The Mean % tissue viability compared to negative control (n=3) of the test substance was determined to be 73.8%. Hence, under the current experimental test conditions it was concluded that test substance was considered to be not irritating to human skin.

 

 

Another, in-vivo skin irritation study was performed in humans to assess the irritation potential of test chemical. The test chemical was applied dermally to the skin of 20 human volunteers at a dose of 4% in petrolatum for 24 hours under occlusive condition. Since only one of the 20 subjects produced skin effects, the test chemical was considered as not irritating to human skin after 24 hours exposure.

 

The above studies were supported by the skin irritation study of test chemical conducted on rabbits. During the study, each rabbit received neat test chemical on intact and abraded skin for 24 hours under occlusive condition and later observed for skin lesions. Since the treated rabbits showed no signs of irritation, the test chemical was considered to be not irritating to the intact and abraded skin of rabbits.

 

All these studies lead to a conclusion that test chemical is indeed not irritating to skin. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical can be classified under the category “Not Classified”.

Eye Irritation:

Acute Eye Irritation/Corrosion Study of Methyl 2-naphthyl ether 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. 0.1 g of test item was 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 item was 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 mg of test item was 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.

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. Hence under the experimental test conditions, Methyl 2-naphthyl ether was considered to be irritating to New Zealand White Female rabbit eyes. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2 (irritating to eyes)”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical was observed in experimental studies. The results obtained from these studies indicate that the chemical is not likely to cause skin irritation but can cause eye irritation. Hence the test chemical can be classified under the category “Not Classified” for skin and “Category 2 (irritating to eyes)” for eye as per CLP.