Registration Dossier

Administrative data

Description of key information

Skin irritation

The substance is considered non-irritant

 

Eye irritation

According to OECD 405 test method, CJ301 showed redness and chemoss indication. However, the overal result does not meet the CLP cirteria, and the response is fully reversible within 48hr. Therefore, CJ301 is not classified.

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:
4 to 4.5 hour exposure
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Source: Kitayama Labes Co., Ltd. (Japan)
- Age at study initiation: approximately 11 to 12 months
- Weight at study initiation: 3595 to 4685 g
- Housing: individually in a stainless steel wire mesh cage
- Water: ad libitum
- Acclimation period: at least 5 days
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 50 ± 20%
- Photoperiod: 12hrs dark / 12hrs light
Preparation of test site:
shaved
Vehicle:
water
Remarks:
Water for injection (WFI, Taiwan Biotech Co., Ltd., Lot: 4KO1838)
Controls:
yes
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.5 g test article was moistened with 0.3 mL water for injection
Duration of treatment / exposure:
4-4.5 hours
Observation period:
1, 24, 48 and 72 hour
Number of animals:
three
Details on study design:
- Area of exposure: left dorsal area
- Washing (if done): with lukewarm water
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: mean of all observation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Remarks on result:
other: mean of all observation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: mean of all observation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: mean of all observation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: mean of all observation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: mean of all observation

Table 1. Individual Body Weights and Clinical Observations

Animal ID

Body weight (g)

Body weight change (g)

Clinical observation

D1

D4

D4-D1

1

3595

3561

-34

Normal

2

4384

4396

12

Normal

3

4685

4748

63

Normal

Table 2. Individual Scores and Total Scores for Skin Irritation During 72 hours

Animal ID

1

2

3

Score on each observation point (hour)

1

24

48

72

1

24

48

72

1

24

48

72

Control site

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

Total irritation score for vehicle*

0

0

0

Test site

Erythema

0

0

0

0

1

1

0

0

0

0

0

0

Edema

0

0

0

0

0

0

0

0

0

0

0

0

Total irritation score for vehicle*

0

1

0

PII**

0.11

* The sum of scores at 24, 48 and 72 hours.

** (Total irritation score for test article-Total irritation score for vehicle)/9

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 404 test method and Draize Dermal Classification System, the PII for CJ301 in intact skin was 0.11 and CJ301 was categorized as mild irritant based on GHS criteria. However, according to ECHA guidance on the application of the CLP Criteria 3.2.2.3.2.2 in vivo data, for up to 3 rabbits test the Skin Irritant Category 2 is used if at least 2 animals show a mean score of 2.3 or above. Therefore, CJ301 is not classified as irritant based on CLP criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315013-IR which is based on the SOP for the OECD 404 (CTPS-TE00440) and OECD 404 (OECD, 2015). The sites were grades for erythema and edema at 1, 24, 48 and 72 hours after the patches removal. No clinical signs of toxicity were found. Body weight changes were within the normal range in all animals. Erythema with score 1 was observed in one animal during 24 hours after patch removal. The Primary Irritation Index for CJ301 was calculated to be 0.11. On the basis of CJ301 given above and according to Draize Dermal Classification System, the response of the test article was categorized as mild irritant.

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:
1 hour exposure
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:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: the animal health research institute, council of agriculture, executive yuan
- Age at study initiation: 4-5 months
- Weight at study initiation: 3304-3493 g
- Housing: individually in a stainless steel wire mesh cage
- Water: ad libitum
- Acclimation period: at least 5 days
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 50 ± 20%
- Photoperiod: 12-hrs dark / 12-hrs light
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
three
Irritation parameter:
iris score
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 48h
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation

Table 1. Individual Body Weights and Clinical Observations

Animal ID

Body weight (g)

Body weight change (g)

Clinical observation

D1

D4

D4-D1

1

3493

3539

46

Normal

2

3304

3428

124

Normal

3

3373

3467

94

Normal

Table 2. Eye Irritation Scores at Observation Point (hours) on Treated Eye

Animal ID

1

2

3

Score on each observation point (hour)

1

24

48

72

1

24

48

72

1

24

48

72

Cornea

Degree of density

0

0

0

0

0

0

0

0

0

0

0

0

Iris

0

0

0

0

0

0

0

0

0

0

0

0

Conjunctiva

Redness

1

2

0

0

2

1

0

0

0

0

0

0

Chemosis

0

0

0

0

1

0

0

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Remarks:
a positive irritant to the eye
Conclusions:
According to OECD 405 test method, CJ301 showed redness and chemoss indication. However, the overal result does not meet the CLP cirteria, and the response is fully reversible within 48hr. Therefore, CJ301 is not classified.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315007-IR which is based on the SOP for the OECD 405 (CTPS-TE00441) and OECD 405 (OECD, 2012).There were no test article effects on mortality, clinical observations and body weight. Reversible redness of conjunctivae with score of 1-2 and chemosis with score of 1 were observed within 24 hours after test article application. CJ301 was given by a single ocular application at 100 mg amount to NZW male rabbits and followed by ocular examination within 72 hours and a 4 days clinical observation period. Conjunctiva redness and chemosis with score 1-2 were determined within 24 hours and fully recovered. On the basis of the test results given above, the response of the test article was judged as a positive irritant to the eye.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The sites were grades for erythema and edema at 1, 24, 48 and 72 hours after the patches removal.No clinical signs of toxicity were found. Body weight changes were within the normal range in all animals. The Primary Irritation Index was calculated to be 0.11. On the basis of the test results given above and according to Draize Dermal Classification System, the response was categorized as mild irritant.

 

Eye irritation

There were no test article effects on mortality, clinical observations and body weight. Reversible redness of conjunctivae with score of 1-2 and chemosis with score of 1 were observed within 24 hours after test article application. The substance was given by a single ocular application at 100 mg amount toNZW male rabbits and followed by ocular examination within 72 hours and a 4 days clinical observation period. Conjunctiva redness and chemosis with score 1-2 were determined within 24 hours and fully recovered. CJ301 showed redness and chemoss indication. However, the overal result does not meet the CLP cirteria, and the response is fully reversible within 48hr. Therefore, CJ301 is not classified.

Justification for classification or non-classification