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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:
07-2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
2-{2-[(2-ethylhexyl)oxy]ethoxy}ethyl prop-2-enoate
Cas Number:
117646-83-0
Molecular formula:
C15H28O4
IUPAC Name:
2-{2-[(2-ethylhexyl)oxy]ethoxy}ethyl prop-2-enoate
Test material form:
liquid
Details on test material:
Test substance name: MI RAMER M1086
Appearance : Clear liquid
Manufacturing date: 2012-03-29
Supplier:Miwon Specialty Chemical Co., Ltd.
Receipt day: 2012-05-23
Deli very amount: 399.223 g(Gross)
Cas No.:117646-83-0
Lot No.:120329JY1
Purit y: 95.55 %
Expiration date: 2013-03-28 (Manufactured after 1 year)
Storage condition: Room temperature [(15 ~ 25)°C

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animal strain and species : Yac:NZW(KBL), Rabbit, SPF
Supplier : Cheonan Yonam college (Sunghwan-up, Seobuk-gu, Chungnam, 331-709, KOREA)
No. of animal and sex distinction at the time of receipt : 5 males
A range of age and body weight at the time of receipt : About 3 months old, 2093.3 ~ 2230.9 g
No. of animal and sex distinction at the time of administration : 4 females
A range of age and body weight at the time of administration : About 3 months old, 2286.5 ~ 2473.1 g

Environmental conditions [Rabbit room No. 2]
The animal room environment was controlled as follows : [temperature (20 ± 3) ℃,relative humidity (50 ± 20) %, the rate of air exchange was (10 ~ 15) times per hourand 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.
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
Each animal was housed individually in stainless steel cages [380(W) ㎜ × 480(D) ㎜ ×300(H) ㎜, Jeongdo Ltd., Korea].
Feed and water
The animals were fed pellet diet for rabbit (Cargill Agri Purina, Inc., 56-4, Soryong-dong, Gunsan-si, Jeollabuk-do, 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)
Amount / concentration applied:
0.1 mL/animal
Duration of treatment / exposure:
-
Observation period (in vivo):
72hrs
Number of animals or in vitro replicates:
4
Details on study design:
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 left 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 right eye wasremained 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 by using the three remaining animals.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
80
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
80
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
80
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
80
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 1h
Score:
12
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
20
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 1h
Score:
10
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24 h
Score:
4
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
20
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 1h
Score:
8
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24 h
Score:
2
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
20
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: 1h
Score:
12
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24 h
Score:
2
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
48 h
Score:
0
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
72 h
Score:
0
Max. score:
20
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 1h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 1h
Score:
2
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 1h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
other: 1h
Score:
2
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible

Applicant's summary and conclusion

Conclusions:
The present study, to investigate the eye irritation/corrosion of MIRAMER M1086, was conducted with NZW rabbits. After application of test substance 0.1 g in the eye of rabbit, parameters measured during 72 hours observation period were mortality, clinical signs, body weight changes and local irritation for 72 hours after application of test substance.
No mortality was observed in the present study and no treatment-related clinical signs were observed in any treated animals. All tested animals showed normal gains in body weight. After application of test substance, eye irritation was observed as conjunctiva redness and chemosis. But the results of the observed sign were restored within 48 hours.
National Institute of Environmental Research (NIER) Notification No. 2010-25 (August 27, 2010), Korea and Globally Harmonized System of Classification and Labelling of Chemicals (GHS), test substance would not be classified as an dermal irritant.
Based on these results, the test substance (MIRAMER M1086) was considered to be mildly irritating substance in this study. Eye irritation was considered slight and reversible reaction.
Executive summary:

The present study, to investigate the eye irritation/corrosion of MIRAMER M1086, was conducted with NZW rabbits. After application of test substance 0.1 g in the eye of rabbit, parameters measured during 72 hours observation period were mortality, clinical signs, body weight changes and local irritation for 72 hours after application of test substance. The following results were obtained.

- 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 weight.

- No corrosive effects were noted on the treated eye of any animal at any of the measuring intervals.

- After application of test substance, eye irritation such as conjunctiva redness, chemosis and discharge were observed. But these observed signs were slight and restored within 48 hours.

- National Institute of Environmental Research (NIER) Notification No. 2010-25 (August 27, 2010), Korea and Globally Harmonized System of Classification and Labelling of Chemicals (GHS), test substance would not be classified as an dermal irritant.

Based on these results, the test substance (MIRAMER M1086) was considered to be mildly irritating substance in this study. Eye irritation was considered slight and reversible reaction.