Registration Dossier

Administrative data

Description of key information

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
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.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
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.
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).
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.

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

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.

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
Study period:
December 03, 2013 to December 09, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
other: NZW(KBL)
Details on test animals or tissues 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, 1831.0 ~ 2070.0 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, 2074.6 ~ 2141.8 gChoice of test system: NZW rabbits are commonly used for this type of acute eye irritation and corrosion study, and there are plenty of reference dataQuarantine 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 eye 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 conditionsThe 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.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
The test substance was applied as a volume of 0.1 mL/animal.
Duration of treatment / exposure:
Single application.
Observation period (in vivo):
6 days
Number of animals or in vitro replicates:
4 (one for the inital test, 3 for the confirmation test).
Details on study design:
Five minutes prior to test substance application, two drops of a topical ocular anesthetic (0.5% proparacaine hydrochloride) were applied to each eye.The test substance was applied as a volume of 0.1 mL/animal, the dose specified in the test guidelines for test substances. The eyes of the animals were examined one day prior to test substance administration. On the day of treatment, the test substance was applied to the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of test substance. The left eye was remained untreated and served as the reference control.A single animal was treated first. As neither a corrosive effect nor a severe irritant effect were observed after the examinations, the test was confirmed using the three remaining animals.ObservationsClinical signs: All animals were daily observed on clinical signs and survival for 6 days after application of test substance.Body weight change: Body weight was measured at animal receipt, just before test substance application and at 72 hours after removal of test substance.Evaluation of eye irritation: On the basis of control left eye, degree and area of opacity of cornea, iris and conjunctivae were observed at 1, 24, 48, 72 hours and until the irritation recovered after application of the test substance according to following table (See Any other information for the table).
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Overall (1hr - 6d)
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Overall (1hr - 6d)
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
other: 1hr - 48 hr
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
other: 72hr - 5d
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
other: 6d
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1hr - 48 hr
Score:
> 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 72hr - 6d
Score:
0
Max. score:
4
Irritant / corrosive response data:
Under the present test conditions, single application of 0.1 mL per animal into the conjunctival sac of the right eye of three rabbits caused the following effects:Animal number 1- On 1 hour, conjunctival redness (grade 2), conjunctival oedema (grade 2) and conjunctival discharge (grade 2) were observed.- On 24 hours, conjunctival redness (grade 2), conjunctival oedema (grade 2) and conjunctival discharge (grade 1) were observed.- On 48 hours, conjunctival redness (grade 2) and conjunctival oedema (grade 1) were observed.- On 72 hours, conjunctival redness (grade 1) were observed.- Conjunctival redness (grade 1) were recovered at 6 days after instillation.Animal number 2- On 1 hour, conjunctival redness (grade 2), conjunctival oedema (grade 2) and conjunctival discharge (grade 2) were observed.- On 24 hours, conjunctival redness (grade 2), conjunctival oedema (grade 2) and conjunctival discharge (grade 2) were observed.- On 48 hours, conjunctival redness (grade 2), conjunctival oedema (grade 1) and conjunctival discharge (grade 1) were observed.- On 72 hours, conjunctival redness (grade 1) were observed.- Conjunctival redness (grade 1) were recovered at 6 days after instillation.Animal number 3- On 1 hour, conjunctival redness (grade 2), conjunctival oedema (grade 2) and conjunctival discharge (grade 2) were observed.- On 24 hours, conjunctival redness (grade 2), conjunctival oedema (grade 1) and conjunctival discharge (grade 1) were observed.- On 48 hours, conjunctival redness (grade 2) and conjunctival oedema (grade 1) were observed.- On 72 hours, conjunctival redness (grade 1) were observed.- Conjunctival redness (grade 1) were recovered at 6 days after instillation.
Other effects:
Mortality rate and clinical signs: The test substance-related clinical signs and dead animals were not observed during the observation period.Body weight: All animals showed normal increase in body weight.

Mortality and clinical signs

Animal number

Days after application

Mortality

0

1

2

3

4

5

6

1

R,O,D

R,O,D

R,O

R

R

R

N

0/3a

2

R,O,D

R,O,D

R,O,D

R

R

R

N

3

R,O,D

R,O,D

R,O

R

R

R

N

N: Normal; R: conjunctival redness; O: conjunctival oedema; D: conjunctival discharge

a: Number of dead animals/Number of total animals

 

Body weight

Animal number

Hours after application (g)

Weight gains (g)

0

72

1

2074.6

2180.5

105.9

2

2123.9

2206.9

83.0

3

2141.8

2196.4

54.6

Mean

2113.4

2194.6

81.2

S.D.

34.8

13.3

25.7

S.D.: Standard deviation

 

Evaluation of eye irritation

Group

T1 (No eye washed)

Animal number

T1-1

T1-2

T1-3

Cornea

Degree of opacity

1 hr

24 hr

48 hr

72 hr

DAY 4

DAY 5

DAY 6

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Iris

1 hr

24 hr

48 hr

72 hr

DAY 4

DAY 5

DAY 6

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Conjunctivae

Redness

1 hr

24 hr

48 hr

72 hr

DAY 4

DAY 5

DAY 6

2

2

2

1

1

1

0

2

2

2

1

1

1

0

2

2

2

1

1

1

0

Oedema

1 hr

24 hr

48 hr

72 hr

DAY 4

DAY 5

DAY 6

2

2

1

0

0

0

0

2

2

1

0

0

0

0

2

1

1

0

0

0

0

Discharge

1 hr

24 hr

48 hr

72 hr

DAY 4

DAY 5

DAY 6

2

1

0

0

0

0

0

2

2

1

0

0

0

0

2

1

0

0

0

0

0

 

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 an eye irritant.
Executive summary:

The present study, to investigate the eye irritation of DEGMEE, was conducted with NZW rabbits. The study was conducted in accordance with the following test regulation:

OECD Guidelines for the Testing of Chemicals, Section 4, TG 405 “Acute eye irritation/corrosion” (October 2, 2012).

 

After application of test substance 0.1 mL in the eye of rabbit, parameters such as mortality, clinical signs, body weight changes and local irritation were measured during 6 days observation period after application of test substance.

The following results were obtained.

- No mortality was observed in the present study.

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

- All tested animals showed normal gain in body weight.

- After application of test substance, eye irritation such as conjunctiva redness, oedema and discharge was observed. But the results of the observed sign were restored within 6 days.

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

 

Based on these results, although the test substance (DEGMEE) was causing the eye irritation, the reaction seems to be reversible.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The substance is not irritating to skin or eyes.


Justification for selection of skin irritation / corrosion endpoint:
Single study available of K1 quality. Study performed in accordance with OECD test guidelines in compliance with GLP.

Justification for selection of eye irritation endpoint:
Single study available of K1 quality. Study performed in accordance with OECD test guidelines in compliance with GLP.

Justification for classification or non-classification