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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:
07-2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system 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 animals and sex distinction at the time of receipt : 4 males
A range of age and body weight at the time of receipt : about 3 months old, 1884.0 ~ 2273.6 g

No. of animals and sex distinction at the time of administration : 3 males
A range of age and body weight at the time of administration : about 3 months old, 2136.6 ~ 2418.9 g
Choice 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 any signs of health or injury were examined. The animals were acclimated for five days when their health statuses were assessed. For study, the animals were used after examined body weight changes and healthy condition.
Identification
Identification cards including information such as study number, test substance name, test title, receipt date, quarantine period, allocation date, experimental period, sex, group number and study director's name.
Remained animal
After animal allocation, a remained animal was euthanized.

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 at least (10 ~ 15) times per hour and lighting was automatically controlled to provide 12 hours of artificial light (08:00 ~ 20:00 hours, 150 ~ 300Lux)]. The feed and water were supplied for acclimation and test period.
Environmental monitoring
The temperatures and relative humidities were continuously monitored per 30 minutes by a computerized system. The luminous intensity, ammonia concentration and noise of animal room 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 in stainless steel cages [380(W) ㎜ × 480(D) ㎜ × 300(H)㎜, Jeongdo Ltd., Korea].
Diet 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 .
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.5 mL/site of prepared test substance was applied to a small area (approximately 6 cm2)
Duration of treatment / exposure:
4 hrs
Observation period:
All animals were daily observed for clinical signs and survival for 72 hours after application of test substance.
Animals were recorded the appearance of each application site at 1, 24, 48 and 72 hours according to Grading of dermal lesions.
Number of animals:
3
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Interpretation of results:
GHS criteria not met
Conclusions:
The present study, to investigate the dermal irritation and corrosion of MIRAMER M1086 was conducted with NZW rabbits. The test substance was applied to the skin of NZW rabbits for 4 hours. Parameters measured during 72 hours observation period were mortality, clinical signs, body weight changes and local irritation.
No mortality was observed in the present study and no treatment-related clinicalsigns were observed in any treated animals. All tested animals showed normal gains in body weights. After application of test substance, the dermal irritation was shown erythema. Skin irritation was observed in very slight erythema until 72 hours. However, from the fourth day after application of the test substance in the healing process was the formation of keratin. The dermal irritation of two animals were restored to normal within one animal 9 days and another animal 10 days.

Based on these results, the test substance (MIRAMER M1086) was considered to be non-irritant in this study.
Executive summary:

The acute dermal irritation potential of MIRAMER M1086 was investigated according to NIER Notification No. 2010-29. The test substance was applied by topical semi-occlusive application of 0.5 mL to the intact skin of the left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. Parameters measured during 72 hours observation period were mortality, clinical

signs, body weight changes and local irritation.

- 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.

- After application of test substance, the dermal irritation was shown erythema.

- 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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
07-2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
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.
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.
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
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.

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

Respiratory irritation

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

Additional information

Justification for classification or non-classification