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Toxicological information

Eye irritation

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Administrative data

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

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 405 (Acute Eye 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 / tissue source

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.

Test system

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).

Results and discussion

In vivo

Resultsopen allclose all
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.

Any other information on results incl. tables

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

 

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 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.