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Toxicological information

Skin irritation / corrosion

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- 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
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

Test animals

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.

Test system

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).

Results and discussion

In vitro

Other effects / acceptance of results:
no data available

In vivo

Results
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.

Any other information on results incl. tables

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

 

 

Applicant's summary and conclusion

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.