Registration Dossier

Administrative data

Description of key information

Skin Irritation:

The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days after patch removal.  Hence, it was concluded that Ethyl 2-naphthyl ether (CAS No. 93-18-5) was not-Irritating to the skin of rats under the experimental conditions tested .Thus it can be concluded that the substance, Ethyl 2 -naphthyl ether (CAS No. 93-18-5) can be classified under the category "Not Classified" as per CLP regulation.

Eye Irritation:

Based on the available data for the target and structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, 2-Ethoxynaphthalene was estimated to be irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, 2-Ethoxynaphthalene can be classified under the category “Category 2”.

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:
guideline study
Justification for type of information:
data is from experimental reports following standard procedures
Qualifier:
according to
Guideline:
other: OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
To determine the dermal reaction profile of Ethyl 2-naphthyl ether (CAS No. 93-18-5) in Sprague Dawley rats.
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Naphthalene, 2-ethoxy-
- Molecular formula : C12H12O
- Molecular weight: 172.226 g/mol
- Substance type: Organic
- SMILES : c12c(ccc(c1)OCC)cccc2
- InChI: 1S/C12H12O/c1-2-13-12-8-7-10-5-3-4-6-11(10)9-12/h3-9H,2H2,1H3
Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Sex: Male and Female
- Source: National Institute of Biosciences, Pune.
- Age at study initiation: Young adult male and female rats aged between 8 – 12 weeks
- Weight at study initiation: The weight range of approximately 222.8 to 255.5 grams at initiation of dosing were used.
Body weights at the start :
Male Female
Mean : 249.84 g (= 100 %)
Minimum : 244.7 g (- 2.06 %)
Maximum : 255.5 g (+ 2.27 %)
Total No. of animals : 5 Mean : 226.06 g (= 100 %)
Minimum : 222.8 g (- 1.44 %)
Maximum : 230.6 g (+ 2.01 %)
Total No. of animals : 5

- Housing:individually housed in polycarbonate cages with paddy husk as bedding
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum):Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period:All animals were acclimatized to laboratory conditions for minimum of 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4 to 22.0 degree centigrade
- Humidity (%): 55.4% to 58.8%.
- Air changes (per hr): ten to fifteen air changes per hour of 100% fresh air that had been passed through the HEPA filters
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
2000 mg/kg
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
10(5/sex)
Details on study design:
TEST SITE
- Area of exposure: Dorsal surface and sides from scapular to pelvic area.
- % coverage: Approximately 10% of the total body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.
- Time after start of exposure: 24 hours
OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : Observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours
on the day of dosing and once daily thereafter for 14 day.
SCORING SYSTEM: Draize Method.
Grading of Skin Reaction
1. Erythema and Eschar Formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight
Eschar formation (injuries in depth) 4
Maximum possible = 4

2. Oedema Formation
No oedema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 mm 3
Severe edema (raised more than 1 mm and extending
Beyond area of exposure) 4
Maximum possible = 4

3. Other dermal abnormalities (not indicative of irritation)
Desquamation………………………………………………………..D
Exfoliation (of eschar)……………………………………………….Ex

Draize, J. H.: Appraisal of the safety of chemicals in foods, drugs and cosmetics: pp 46-49 Assoc. of food and drug officials of the united states, Topka, Kansas (1965).
Other effects / acceptance of results:
no data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
14 d
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.

Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Other effects:
Clinical Signs of Toxicity and Mortality
Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. All animals survived through the study period of 14 days.
Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. All animals survived through the study period of 14 days.

Body Weight
Sex : Male
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 8.77% and 18.10% respectively.

Sex : Female
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.11% and 11.40% respectively.

Gross Pathological Findings
Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.

Summary of Evaluation of Dermal Reaction

Test System : Sprague Dawley Rat

Sex : Male

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

 

Animal Nos.

Period of signs

in days

 From - to

 

Mortality

I

2000

No dermal reaction observed

5

1 - 5

Day 0 - Day 14

0/5

Sex : Female

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

 

Animal Nos.

Period of signs

in days

 From - to

 

Mortality

I

2000

No dermal reaction observed

5

6 - 10

Day 0 - Day 14

0/5

Individual Animal - Evaluation of Dermal Reaction

Sex : Male  

Group : I

Dose  : 2000 mg/kg body weight

Animal

Dermal

D A Y S

No.

Reaction

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

5

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

 Sex : Female  

Group : I

Dose  : 2000 mg/kg body weight

Animal

Dermal

D A Y S

No.

Reaction

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

6

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

7

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

8

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

9

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

10

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Summary of Clinical Signs of Toxicity and Mortality

 

Laboratory Test Item Code :TAS/122/048

Test System : Sprague Dawley Rat

Sex : Male

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

I

2000

No clinical signs observed

5

1 - 5

Day 0 - Day 14

0/5

Sex : Female

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

I

2000

No clinical signs observed

5

6 - 10

Day 0 - Day 14

0/5

Mean Body Weight and Percent Body Weight Gain (g)

 

Laboratory Test Item Code :TAS/122/048

Test System : Sprague Dawley Rat

Sex : Male

Group No.

Dose

(mg/kg body weight)

 

Body weight Day 0

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

2000

Mean

249.84

271.82

8.77

295.12

8.57

18.10

± SD

4.50

10.00

2.30

10.93

0.33

2.60

 

 

 

Sex : Female

Group No.

Dose

(mg/kg body weight)

 

Body weight Day 0

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

2000

Mean

226.06

239.92

6.11

251.88

4.98

11.40

± SD

3.30

7.03

1.66

7.90

0.74

1.99

 

Summary of Gross Pathological Findings

 

Laboratory Test Item Code :TAS/122/048

Test System : Sprague Dawley Rat

Sex : Male

Group No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

2000

1 - 5

TS

No abnormality detected

Sex : Female

Group No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

2000

6 - 10

TS

No abnormality detected

                     TS = Terminal Sacrifice

 

Individual Animal -Clinical Signs of Toxicity and Mortality

 

Laboratory Test Item Code :TAS/122/048

Test System : Sprague Dawley Rat

Sex : Male

Group

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

 

Mortality

I

2000

No clinical signs observed

5

1

Day 0 - Day 14

0

2

Day 0 - Day 14

0

3

Day 0 - Day 14

0

4

Day 0 - Day 14

0

5

Day 0 - Day 14

0

Sex : Female

Group

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

 

Mortality

I

2000

No clinical signs observed

5

6

Day 0 - Day 14

0

7

Day 0 - Day 14

0

8

Day 0 - Day 14

0

9

Day 0 - Day 14

0

10

Day 0 - Day 14

0

 

 

Interpretation of results:
other: not irritating
Conclusions:
The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days after patch removal. Hence, it was concluded that Ethyl 2-naphthyl ether (CAS No. 93-18-5) was not Irritating to the skin of rats under the experimental conditions tested .Thus it can be concluded that the substance, Ethyl 2-naphthyl ether (CAS No. 93-18-5) can be classified under the category "Not Classified" as per CLP regulation.
Executive summary:

A study was designed and conducted to determine the dermal reaction profile of Ethyl 2-naphthyl ether (CAS No. 93-18-5) in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures.

The animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days after patch removal.  Hence, it was concluded that Ethyl 2-naphthyl ether (CAS No. 93-18-5) was not-Irritating to the skin of rats under the experimental conditions tested .Thus it can be concluded that the substance, Ethyl 2-naphthyl ether (CAS No. 93-18-5) can be classified under the category "Not Classified" as per CLP regulation.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Weight of evidence approach based on similar chemicals
Justification for type of information:
Weight of evidence approach based on similar chemicals
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
other: Weigth of evidence based on structurally similar chemicals
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the ocular irritation potential of 2-Ethoxynaphthalene
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 2-Ethoxynaphthalene
- Molecular formula: C12H12O
- Molecular weight: 172.226 g/mole
- Smiles notation: c12c(ccc(c1)OCC)cccc2
- InChl: 1S/C12H12O/c1-2-13-12-8-7-10-5-3-4-6-11(10)9-12/h3-9H,2H2,1H3
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
1. 0.1 g
2. undiluted
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
1. 1, 24, 48, 72 hour, day 7, day 14 and day 21
2. 24 hours
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
3
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Signs of irritation observed
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Based on the available data for the target and structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, 2-Ethoxynaphthalene was estimated to be irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, 2-Ethoxynaphthalene can be classified under the category “Category 2”.
Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the ocular irritation potential of 2-Ethoxynaphthalene.

Acute Eye Irritation/Corrosion Study of the test chemical was performed as per OECD guideline no. 405. 3 female New Zealand White rabbits were used for the study.

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 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. 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 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 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 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. 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)” to Female New Zealand White rabbit eyes.

 

This is supported by the results of another study performed to assess the ocular irritation potential of the structurally similar chemical in rabbits. The test chemical was instilled into the eyes of 3 New Zealand White rabbits and observed for effects.

One hour after exposure, only slight redness and swelling of the conjunctivae and slight ocular discharge were reported. Average Draize scores for conjunctival oedema and chemosis, and ocular discharge were 0.33. After 24 hours there were no signs of ocular irritation reported.

Hence, the test chemical was considered to be slightly irritating to rabbit eyes.

Based on the available data for the target and structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, 2-Ethoxynaphthalene was estimated to be irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, 2-Ethoxynaphthalene can be classified under the category “Category 2”.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

Various studies have been summarized to determine the level of dermal irritation/ corrosion caused by 2-Ethoxynaphthalene in living organisms. These studies include in vivo experimental results on rats, rabbits and humans for the target and its structurally similar chemicals. The experimental results have also been compared with estimated results.

A study was designed and conducted to determine the dermal reaction profile of Ethyl 2-naphthyl ether (CAS No. 93-18-5) in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures.

The animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days after patch removal.  Hence, it was concluded that Ethyl 2-naphthyl ether (CAS No. 93-18-5) was not-Irritating to the skin of rats under the experimental conditions tested .Thus it can be concluded that the substance, Ethyl 2 -naphthyl ether (CAS No. 93-18-5) can be classified under the category "Not Classified" as per CLP regulation.

This guideline study is supported by the results of a skin irritation study performed in humans to assess the irritation potential of 2-Ethoxynaphthalene.

2-Ethoxynaphthalene was tested 2% in petrolatum on 25 human volunteers in a 48 hours closed patch test. 2-Ethoxynaphthalene was not irritating to humans after 48 hours exposure.

The above results are supported by a similar study performed in rabbits to determine the dermal irritation potential of 2-ethoxynaphtalene. 2-ethoxynaphthalene was applied in undiluted form to the intact and abraded skin of rabbits under occlusion for 24 hours. The rabbits were observed for signs of irritation.

Skin irritation effects were also estimated by four different models i.e, Battery, leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for chemical 2-Ethoxynapthalene.

Based on estimation, No severe skin irritation effect were known when test chemical, 2-Ethoxynapthalene was exposed to rabbit skin.

Hence, 2-Ethoxynapthalene can be considered not irritating to skin.

The experimental and estimated results for the target chemical are in mutual agreement with each other indicating a strong possibility of 2-Ethoxynaphthtalene being not irritating to skin.

These results are further supported by the an Acute Dermal Irritation/corrosion Study performed as per OECD guideline No. 404 to assess the irritation potential of the structurally similar chemical.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 oedema at 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 concluded that the test chemical was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested and classified as "Not Classified" as per CLP criteria.

Based on the available data for the target and structurally similar read across substances, it can be concluded that 2-Ethoxynaphthalene can be considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, 2-Ethoxynaphthalene can be classified under the category “Not Classified”.

Eye irritation:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the ocular irritation potential of 2-Ethoxynaphthalene.

Acute Eye Irritation/Corrosion Study of the test chemical was performed as per OECD guideline no. 405. 3 female New Zealand White rabbits were used for the study.

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 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. 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 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 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 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. 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)” to Female New Zealand White rabbit eyes.

 

This is supported by the results of another study performed to assess the ocular irritation potential of the structurally similar chemical in rabbits. The test chemical was instilled into the eyes of 3 New Zealand White rabbits and observed for effects.

One hour after exposure, only slight redness and swelling of the conjunctivae and slight ocular discharge were reported. Average Draize scores for conjunctival oedema and chemosis, and ocular discharge were 0.33. After 24 hours there were no signs of ocular irritation reported.

Hence, the test chemical was considered to be slightly irritating to rabbit eyes.

Based on the available data for the target and structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, 2-Ethoxynaphthalene was estimated to be irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, 2-Ethoxynaphthalene can be classified under the category “Category 2”.

Justification for classification or non-classification

Available studies for 2-ethoxynaphthalene indicates that it is not likely to cause any irritation to skin.

Hence, 2-ethoxynaphthalene can be considered to be not irritating to skin. It can be further classified under the category "Not Classified" as per CLP Regulation.

The results of the experimental studies from the structurally similar read across substances indicate a possibility that 2-Ethoxynaphthlene can cause irritation to eyes. Hence by applying the weight of evidence approach, 2-Ethoxynaphthalene can be considered to be irritating to eyes. It can be further classified under the category "Category 2" as per CLP regulation.