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Administrative data

Description of key information

Skin irritation

The Primary Irritation Index (PII) of CJ306 was 0 and CJ 306 was categorized as non-irritant to the skin (OECD TG404).

 

Eye irritation

CJ 306 was judged as a positive irritant to the eye(OECD TG405).

 

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:
From March 09, 2016 to April 26, 2016
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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
- Source: the animal health research institute, council of agriculture, executive yuan.
- Age at study initiation: approximately 3 to 4 months
- Weight at study initiation: 2646 to 3014 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
Controls:
yes, concurrent vehicle
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.5 g test article was moistened with 0.5 mL water for injection
Duration of treatment / exposure:
4-4.5 hours
Observation period:
1, 24, 48, 72 hours
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)
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation

Table 1. Individual Body Weights and Clinical Observations Table 1. Individual Body Weights and Clinical Observations

Animal ID

Body weight (g)

Body weight change (g)

Clinical observation

D1

D4

D4-D1

1

2646

2769

123

Normal

2

2786

2853

67

Normal

3

3014

3046

32

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

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

PII**

0

* 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 CJ306 in intact skin was 0 and CJ306 was categorized as non-irritant. Therefore, CJ306 was not met classification on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315016-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. All scores of erythema and edema were 0 during 72 hours after patch removal. The Primary Irritation Index for CJ306 was calculated to be 0. On the basis of the test results given above and according to Draize Dermal Classification System, the response of CJ306 was categorized as non-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:
From April 15, 2016 to June 01, 2016
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
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: 2918-3614 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 hrs
Observation period (in vivo):
1 hr, 24 hr, 48 hr, 72 hr, 7 day, 14 day
Number of animals or in vitro replicates:
Three
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
2 more reaction ones
Time point:
24/48/72 h
Score:
1.9
Max. score:
2
Reversibility:
fully reversible within: 14 day
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
2 more reation ones
Time point:
24/48/72 h
Score:
0.5
Max. score:
1
Reversibility:
fully reversible within: 72 hr
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
2 higher rection ones
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
2 more reaction ones
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive 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

10

2957

3011

54

Normal

11

2918

2913

-5

Normal

12

3614

3661

47

Normal

Table 2. Eye Irritation Scores at Observation Point on Treated Eye

Animal ID

10

11

12

Score on each observation point

1

hr

24hr

48hr

72

hr

7

day

14 day

1

hr

24

hr

48 hr

72 hr

7

day

14

day

1

hr

24

hr

48

hr

72

hr

7

day

14

day

Cornea

Degree of density

3

2

2

2

1

0

0

1

2

2

2

0

0

0

0

0

0

0

Area1of opacity

3

4

1

3

2

0

0

2

1

2

2

0

0

0

0

0

0

0

Iris

NA

1

0

0

02

0

0

1

1

02

02

0

0

02

0

02

02

0

Conjunctiva

Redness

2

3

2

2

1

0

0

3

3

1

1

0

1

1

1

1

1

0

Chemosis

2

4

4

2

0

0

1

3

2

1

1

0

2

1

1

0

1

0

1:Score 1: 1/4 (or less) not zero; Score 2: greater than 1/4 but less than 1/2; Score 3: greater that 1/2, but less than 3/4; Score 4: greater than 3/4, up to whole area.

2:Iris discoloration

NA: the iris could not be observed since cornea opacity

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
According to OECD 405 test method, CJ306 showed that positive irritant to the eye and reversible. Therefore, CJ306 was categorized as irritating to eyes (Category 2) base on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315010-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.CJ306 was given by a single ocular application at 100 mg amount toNZW male rabbits andfollowed by ocular examination and clinical observation for 14 days. Reversible corneal opacity, hyperemia of iris, and conjunctiva redness and chemosis were observed within 14 days.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:
adverse effect observed (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 for CJ306 was calculated to be 0. On the basis of the test results given above and according to Draize Dermal Classification System, the response of CJ306 was categorized as non-irritant.

 

Eye irritation

There were no test article effects on mortality, clinical observations and body weight.CJ306 was given by a single ocular application at 100 mg amount toNZW male rabbits and followed by ocular examination and clinical observation for 14 days. Reversible corneal opacity, hyperemia of iris, and conjunctiva redness and chemosis were observed within 14 days.On the basis of the test results given above, the response of the test article was judged as a positive irritant to the eye.

Justification for classification or non-classification

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