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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
Study period:
December 03, 2013 to December 06, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD test guidelines in compliance with GLP.

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 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: Clear colorless liquid
Details on test material:
Name: DEGMEE
CAS No.: 1002-67-1
Lot No.: 20130625
Storage condition: Room temperature [(1 ~ 30) ℃]
Expiration date: 2014-06-25
Appearance: Clear colorless liquid
Purity: 99.98 %
Molecular formula / MW: C2H5O(CH2CH2O)2CH3 / 148.20

Test animals

Species:
rabbit
Strain:
other: NZW(KBL)
Details on test animals and environmental conditions:
Animal strain and species: Yac:NZW(KBL), Rabbit, SPFSupplier: Cheonan Yonam college (Sunghwan-up, Seobuk-gu, Cheonan-si, Chungcheongnam-do, 331-709, Korea)No. of animals and sex distinction at the time of receipt: 4 femalesA range of age and body weight at the time of receipt: About 3 months old, 1895.5 ~ 1935.4 gNo. of animals and sex distinction at the time of administration: 3 femalesA range of age and body weight at the time of administration: About 3 months old, 2000.5 ~ 2060.2 gChoice of test system: NZW rabbits are commonly used for this type of acute dermal irritation and corrosion study, and there are plenty of reference data.Quarantine and acclimation: On receipt the animals were examined for any signs of health or injury. The animals were acclimated for 5 days when their health statuses were assessed. For study, the animals were used after they were examined body weight changes, health condition and skin condition.Identification: Identification cards including information such as study number, test substance name, test title, receipt date, quarantine and acclimation period, allocation date, experimental period, sex, animal number and study director's name were indicated.Remained animal: After animal allocation, remained animal was euthanized.Environmental conditions: The animal room environment was controlled as follows : [temperature (20 ± 3) ℃, relative humidity (50 ± 20) %, the rate of air exchange were (10 ~ 15) times per hour and lighting was automatically controlled to provide 12 hours of artificial light (08:00 ~ 20:00 hours, 150 ~ 300 Lux)]. The feed and water were supplied for acclimation and test period ad libitum .Environmental monitoring: The temperatures and relative humidities were automatically monitored every 30 minutes by a computerized system. The luminous intensity, ammonia concentration and noise of animal room were measured once per quarter periodically. The environmental conditions were considered not to have affected the purpose or integrity of the study.Housing: The animals were housed individually in stainless steel cages [670(W) mm x 500(D) mm x 340(H) mm, Jeongdo Ltd., Korea].Feed and water: The animals were fed pellet diet for rabbit (Cargill Agri Purina, Inc., 56-4, Soryong-dong, Gunsan-si, Jeonbuk, Korea) and given the filtered and UV irradiated water ad libitum.Contaminant confirmation of feed and water: The diet was considered not to contain any contaminant based on the periodical analysis results report of manufacturer and water did not contain any contaminant based on periodical analysis in accordance with the SOP of Korea Testing &Research Institute.

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL/site of test substance was applied to a small area.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 (1 for the inital test, 2 for the confirmation test).
Details on study design:
Application methodOn the day prior to the application, the back of each rabbit was clipped free of hairs. Onto the one site of the back, 0.5 mL/site of test substance was applied to a small area (approximately 6 cm2) of skin and covered with a gauze patch, which was held in place with non-irritating tape. The entire trunk of the animals were wrapped with non-toxic adhesive tape (TegadermTM, 3MTM) for 4 hours. After removal the patch, the applied sites were washed out gently with sterilized distilled water.Initial test (in vivo dermal irritation/corrosion test using one animal)Test substance was applied sequentially to an animal. The first patch was removed after three minutes, the second patch was applied to a different site and removed after one hour, and the third patch was applied to a different site and removed after four hours. The test substance did not induce serious dermal irritation and corrosion response when three test patches were applied sequentially to the animal.Confirmatory test (in vivo dermal irritation test with additional animals)The confirmatory test was conducted, because corrosive effect was not observed in the initial test. Two animals were treated with a single patch, which was removed after four hours.ObservationsClinical signsAll animals were daily observed on clinical signs and survival for 72 hours after removal of test substance.Body weight changeBody weight was measured at animal receipt, just before test substance application and at 72 hours after removal of test substance.Observation of application siteThe applied sites were observed irritations such as erythema, eschar and oedema at 1, 24, 48, 72 hours after removal of the test substance.Evaluation of dermal irritationAnimals were recorded the appearance of each application site for 72 hours after removal of the test substance according to Grading of dermal lesions (reported in table form – see Any other information).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Under the present test conditions, dermal irritation was not observed in any of the treated animals.
Other effects:
The test substance-related clinical signs and dead animals were not observed during the observation period.All animals showed normal increase in body weight.

Any other information on results incl. tables

Mortality and clinical signs

Animal number

Days after application

Mortality

0

1

2

3

1

N

N

N

N

0/3a

2

N

N

N

N

3

N

N

N

N

N: Normal

a: Number of dead animals/Number of total animals

 

Body weight

Animal number

Hours after application (g)

Weight gains (g)

0

72

1

2050.4

2126.7

76.3

2

2060.2

2143.5

83.3

3

2000.5

2163.2

162.7

Mean

2037.0

2144.5

107.4

S.D.

32.0

18.3

48.0

S.D.: Standard deviation

 

Evaluation of dermal irritation

Change

Erythema & Eschar

Oedema

Animal No.

Phases1

1

2

3

1

2

3

 

1 hour

0

0

0

0

0

0

24 hours

0

0

0

0

0

0

48 hours

0

0

0

0

0

0

72 hours

0

0

0

0

0

0

1: Examinations were performed at the specified times after instillation of the test

 

Skin irritation scores – mean values after 24, 48 and 72 hours

Animal Number

Erythema

N

Oedema

N

1

0.0

3

0.0

3

2

0.0

3

0.0

3

3

0.0

3

0.0

3

N = number or time of available data points

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Based upon the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), DEGMEE would not be classified as a dermal irritant.
Executive summary:

The acute dermal irritation potential of DEGMEE was investigated according to OECD test guideline No. 404. The test substance was applied by topical semi-occlusive application of 0.5 mL to the intact skin of the one site of the back of each of three young adult New Zealand White rabbits. The duration of treatment was four hours.

The scoring of skin reactions were performed until 72 hours after removal of the dressing.

 

- No mortality was observed in the present study.

- No treatment-related clinical signs were observed in any treated animals.

- All tested animals showed normal gains in body weights.

- After application of test substance, no dermal irritation was observed in this study.

- Based upon the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), DEGMEE would not be classified as a dermal irritant.

 

Based on these results, the test substance (DEGMEE) was not causing the dermal irritation.