Registration Dossier

Administrative data

Description of key information

Skin irritation:

Two in vivo skin irritation studies are available.

The key study was conducted in accordance with GB/T 21604-2008 Chemicals-Test method of acute dermal irritation/corrosion (equal to OECD 404) using rabbit.  No sign of erythema and edema was observed at the skin of the four rabbits during 24h to 72 h.

The supporting study evaluated the primary skin irritation potential of test item using only 2 male rabbits with method similar to OECD 404 with deviation. The test item is minimally irritating to the skin.

Eye Irritation:

Two in vivo eye irritation studies are available.

The key study assessed the irritation/corrosion effects of the test substance on eyes of rabbit in accordance with GB/T 21609-2008 Chemicals - Test method of acute eye irritation/corrosion (similar to OECD 405). The mean cornea opacity and iris scores at 24, 48 and 72 h for each animal were all 0. The mean conjunctivae scores were 0.67, 1.33, 0.33, 1 and the mean chemosis scores were 0, 1, 0, 0.33, respectively at 24, 48 and 72 h. All the irritations disappeared within 4 days.

 

The supporting study evaluated the primary eye irritation potential of test item using only 2 male rabbits with method similar to OECD 405 with deviations. The test item is Moderately irritating to the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2014-12-09 to 2014-12-13
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: GB/T 21604-2008 Chemicals-Test method of acute dermal irritation/corrosion
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
authorized by CNAS
Specific details on test material used for the study:
- Purity: 100.0%
- Lot No.: KNC110310
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Tianqin biotechnology Ltd., Changsha
- Weight at study initiation: 1.9 - 2.2 kg
- Housing: housed in common environment
- Diet: AII of the feeds were supplied by Tianqin Biotechnology Ltd., Changsha
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 54-65
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
other: methylcellulose
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration (if solution): 1 g/mL

VEHICLE
- Concentration (if solution): 1 % methylcellulose solution

NEGATIVE CONTROL
Adjacent areas of untreated skins of each rabbit served as control for the test.
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
2 males and 2 females
Details on study design:
TEST SITE
- Preparation of test area: Approximately 24 h before the test, about 3 cm x3 cm areas of fur was removed from both left and right sides of the animals dorsal. Only the animals with healthy intact skins was used.
- Exposure: A volume of 0.5 mL of the test substance was applied uniformly to a small area of skins on the left sides of the animals. The test substance was covered with a gauze patch with two layers, which was fixed with nonirritating tapes throughout the 4-h exposure period.

REMOVAL OF TEST SUBSTANCE
At the end of the exposure period, the residual test substance was removed with water.

OBSERVATION TIME POINTS
The signs of skin irritation at application site were observed at 24, 48 and 72 h after patch removal.

SCORING SYSTEM:
- Method of calculation: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: for all animals tested
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: for all animals tested
Irritant / corrosive response data:
No sign of erythema and edema was observed at the skin of the four rabbits during 24h to 72 h.
Other effects:
Individual body weights were rising after exposing.
Interpretation of results:
GHS criteria not met
Remarks:
Not irritant
Conclusions:
The results of the acute dermal irritation/corrosion test showed that the highest average of score was 0 ( 24 - 72 h), and dermal irritation intensity of test item was no irritation.
Executive summary:

The irritation/corrosion effect of the test substance on the skin of mammals were determined using rabbit in accordance with GB/T 21604-2008 Chemicals-Test method of acute dermal irritation/corrosion.

 

No sign of erythema and edema was observed at the skin of the four rabbits during 24h to 72 h. Individual body weights were rising after exposing.

 

Thus the highest average of score was 0 ( 24 - 72 h), no irritation to the animals skin was concluded.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 2010-03-23 to 2010-04-05
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable study report which meets basic scientific principles. The animals were tested for skin and eye irritation at the same time; only 2 animals were used, simultaneously; few details in study report.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted in Apr 2002
Deviations:
yes
Remarks:
animals were tested for skin and eye irritation ; only 2 animals were exposed; few details in study report.
GLP compliance:
no
Specific details on test material used for the study:
- Analytical purity: 100%
- Lot/batch No.: 10SC8156928-2-2
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kitayama Labes Co., Ltd.
- Age at study initiation: 21 weeks
- Weight at study initiation: 3.18 - 3.20 kg (range)
- Housing: the animals were individually housed in aluminium suspended cages with stainless steel mesh in the front and floor, w450 x d550 x h350 mm (Yamato Scientific Co., Ltd., Tokyo, Japan). Cages were exchanged with washed, sterile cages every 2 weeks.
- Diet: app. 120 g/day pellet diet for rabbits, LCR-4 (Oriental Yeast Co., Ltd., Japan)
- Water: tap water via automated water supply equipment (Labo Engineering Co.Ltd., Japan.), ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50 ± 20
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated skin served as the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test substance was moistened with 0.4 mL of distilled water
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals:
2 males
Details on study design:
TEST SITE
- Area of exposure: dorsal area

REMOVAL OF TEST SUBSTANCE
- Washing (if done): absorbent cotton with water was used to wipe the application site and remove the test substance
- Time after start of exposure: 4 h

SCORING SYSTEM:
Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
out of 2 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of 2 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Irritant / corrosive response data:
In the observation after application, erythema (score; 1) was observed in 2 animals and edema (score; 1) was observed in 1 out of 2 animals. All of these local reactions disappeared after 24 hours.

Results of the skin irritation test:

Animal number

Reaction

Skin reaction grade (score)

Time after removal of the patch

1 hour

24 hour

48 hour

72 hour

1

Male

Erythema

 

Edema

1

 

0

0

 

0

0

 

0

0

 

0

2

Male

Erythema

 

Edema

1

 

1

0

 

0

0

 

0

0

 

0

Interpretation of results:
not classified
Conclusions:
Based on the results obtained, it is concluded that the test item is Minimally irritating to the skin.
Executive summary:

The primary skin irritation potential of test item was evaluated using 2 male rabbits with method similar to OECD 404.

In the observation after application, erythema (score; 1) was observed in 2 animals and edema (score; 1) was observed in 1 out of 2 animals. All of these local reactions disappeared after 24 hours.

Based on the results obtained, it is concluded that the test item is Minimally irritating to the skin.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2014-12-09 to 2014-12-14
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: GB/T 21609-2008 Chemicals - Test method of acute eye irritation/corrosion
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
authorized by CNAS
Specific details on test material used for the study:
- Purity: 100.0%
- Lot No.: KNC110310
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Tianqin biotechnology Ltd., Changsha
- Weight at study initiation: 2.0 ~ 2.3 kg
- Housing: housed in common environment
- Diet: All ofthe feeds were supplied by Tianqin Biotechnology Ltd., Changsha
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 57-62
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Observation period (in vivo):
4 day
Number of animals or in vitro replicates:
2 female and 2 male
Details on study design:
- Treatment of the test substance: An appropriate amount of the test substance was grinded
- Exposure: The animal left eyelid was opened lightly, and about 100 mg of the test substance was applied on the cornea, the lids are then gently held together for one second.
- Observation: The eyes were examined at 1h, 24h, 48h, 72 h and the 4th day, and the scores were recorded.

SCORING SYSTEM: Draize
Irritation parameter:
cornea opacity score
Basis:
other: All 4 animal tested
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
other: all 4 animal tested
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 4 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48h
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal: #1 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 4 d
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48h
Irritant / corrosive response data:
One hour after administration, the conjunctiva of the rabbits signed No.1 and No.2 were cardinal red congestion and light dropsy and having more excretion. The conjunctiva of the rabbits signed No.3 and No.4 were bright red congestion and light dropsy and having a small amount excretion. Twenty-four hours after administration, the conjunctiva of the rabbits signed No.2 and No.4 were cardinal red congestion and light dropsy and having a great quantity excretion. The dropsy of the conjunctiva of the rabbits signed No.1 and No.3 disappeared. Forty-eight hours after administration, the irritation of the four rabbits lightened. And the eye of the rabbits signed No.1, No.3 and No.4 recovered in the time of 72 h after administration. The eye of the rabbits signed No.2 recovered in the time of the 4th day. The irritation of Cornea and Iris were not observed.
Other effects:
Individual body weights were rising after exposing.

Eye Damage and Scoring:

 

Female #1

Female #2

Male #3

Male #4

1h

24h

48h

72h

1h

24h

48h

72h

1h

24h

48h

72h

1h

24h

48h

72h

cornea opacity

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

conjunctivae

2

1

1

0

2

2

1

1

1

1

0

0

1

2

1

0

chemosis

1

0

0

0

1

1

1

1

1

0

0

0

1

1

0

0

Iris

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Remarks:
Not classified
Conclusions:
The mean cornea opacity and iris scores at 24, 48 and 72 h for each animal were all 0. The mean conjunctivae scores were 0.67, 1.33, 0.33, 1 and the mean chemosis scores were 0, 1, 0, 0.33, respectively at 24, 48 and 72 h after installation. All the irritations disappeared within 4 days.
Executive summary:

The irritation/corrosion effects of the test substance on eyes of rabbit were assessed in accordance with GB/T 21609-2008 Chemicals - Test method of acute eye irritation/corrosion.

100 mg of the test substance was applied on the left cornea of 2 female and 2 male White New Zealand rabbits. The untreated right eye was used as control.

The mean cornea opacity and iris scores at 24, 48 and 72 h for each animal were all 0. The mean conjunctivae scores were 0.67, 1.33, 0.33, 1 and the mean chemosis scores were 0, 1, 0, 0.33, respectively at 24, 48 and 72 h. All the irritations disappeared within 4 days.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 2010-03-23 to 2010-04-05
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable study report which meets basic scientific principles. The animals were tested for skin and eye irritation at the same time; only 2 animals were used, simultaneously; few details in study report.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in Apr 2002
Deviations:
yes
Remarks:
animals were tested for skin and eye irritation; only 2 animals were exposed; few details in study report
GLP compliance:
no
Specific details on test material used for the study:
- Analytical purity: 100%
- Lot/batch No.: 10SC8156928-2-2
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kitayama Labes Co., Ltd.
- Age at study initiation: 21 weeks
- Weight at study initiation: 3.18 - 3.20 kg (range)
- Housing: the animals were individually housed in aluminium suspended cages with stainless steel mesh in the front and floor, w450 x d550 x h350 mm (Yamato Scientific Co., Ltd., Tokyo, Japan). Cages were exchanged with washed, sterile cages every 2 weeks.
- Diet: app. 120 g/day pellet diet for rabbits, LCR-4 (Oriental Yeast Co., Ltd., Japan)
- Water: tap water via automated water supply equipment (Labo Engineering Co. Ltd.,Japan), ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50 ± 20
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
1 week
Reading time points: 1, 24, 48, 72 and 96 h, and 7 days
Number of animals or in vitro replicates:
2 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

SCORING SYSTEM:
Draize scoring system
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of 2 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
1.33
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
One hour after application, 2/2 rabbits had slight conjunctivae redness (score 1) and moderate chemosis (score 2). At the 24-hours reading time point, moderate conjunctivae redness (score 2) and moderate to severe chemosis (score 2 to 3) were observed in 2/2 animals, and 1 out of 2 rabbits had slight reaction in cornea (score 1). At 48, 72 and 96 reading time points, 2/2 rabbits had slight conjunctivae redness (score 1) and slight chemosis (score 1). All eye irritation effect had cleared within 7-days reading time point. No irritation reactions were observed in the iris.

Table 1: individual irritation scores

 

Time

 

conjunctivae

 

iris

 

cornea

 

 

redness

chemosis

Rabbit 1

1 h

1

2

0

0

 

24 h

2

3

0

1

 

48 h

1

1

0

0

 

72 h

1

1

0

0

 

96 h

1

1

0

0

 

7 days

0

0

0

0

 

Average*

1.33

1.67

0.0

0.33

Rabbit 2

1 h

1

2

0

0

 

24 h

2

2

0

0

 

48 h

1

1

0

0

 

72 h

1

1

0

0

 

96 h

1

1

0

0

 

7 days

0

0

0

0

 

Average*

1.33

1.33

0.0

0.0

* mean of 24 + 48 + 72 h

Interpretation of results:
not irritating
Conclusions:
Based on the results obtained, it is concluded that the test item is Moderately irritating to the eye.
Executive summary:

The primary eye irritation potential of test item was evaluated using 2 male rabbits with method similar to OECD 405.

One hour after application, 2/2 rabbits had slight conjunctivae redness (score 1) and moderate chemosis (score 2). At the 24-hours reading time point, moderate conjunctivae redness (score 2) and moderate to severe chemosis (score 2 to 3) were observed in 2/2 animals, and 1 out of 2 rabbits had slight reaction in cornea (score 1). At 48, 72 and 96 reading time points, 2/2 rabbits had slight conjunctivae redness (score 1) and slight chemosis (score 1). All eye irritation effect had cleared within 7-days reading time point. No irritation reactions were observed in the iris.

Based on the results obtained, it is concluded that the test item is Moderately irritating to the eye.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Skin irritation:

In vivo, GB/T 21604-2008, similar to OECD 404:

Mean scores at 24, 48 and 72 hours after patch removal: erythema/eschar: 0 for all animals tested; oedema: 0 for all animals tested.

In vivo, similar to OECD 404 with deviations (The animals were tested for skin and eye irritation at the same time; only 2 animals were used): Mean scores at 24, 48 and 72 hours after patch removal: erythema/eschar: 0 for all animals tested; oedema: 0 for all animals tested.

According to Regulation (EC) No 1272/2008, section 3.2.2.1 and Table 3.2.2, this substance should not be classified for this endpoint.

 

Eye irritation:

In vivo, GB/T 21609-2008, similar to OECD 405:

The mean cornea opacity and iris scores at 24, 48 and 72 h for each animal were all 0. The mean conjunctivae scores were 0.67, 1.33, 0.33, 1 and the mean chemosis scores were 0, 1, 0, 0.33, respectively at 24, 48 and 72 h. All the irritations disappeared within 4 days.

In vivo, similar to OECD 405 with deviations (The animals were tested for skin and eye irritation at the same time; only 2 animals were used): Mean scores at 24, 48 and 72 h for each animal: cornea opacity: 0.33, 0; iris: 0, 0; conjunctivae: 1.33, 1.33; chemosis: 1.67, 1.33

According to Regulation (EC) No 1272/2008, table 3.3.1 and 3.3.2, this substance should not be classified for this endpoint.