Registration Dossier

Administrative data

Description of key information

Skin irritation

The Primary Irritation Index (PII) of CJ304 was 0 and CJ304 was categorized as non skin irritant (OECD TG404).

 

Eye irritation

CJ304 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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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: 2563 to 2726 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
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
Water for injection
Controls:
yes, concurrent vehicle
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.5 g test article was moistened with 0.45 mL water for injection
Duration of treatment / exposure:
4-4.5 hours
Observation period:
1, 24, 48 and 72 hours
Number of animals:
three
Irritation parameter:
primary dermal irritation index (PDII)
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

2716

2903

187

Normal

2

2726

2826

100

Normal

3

2563

2667

104

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 CJ304 in intact skin was 0 and CJ304 was categorized as non-irritant. CJ304 was not met classification on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315015-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 CJ304 was calculated to be 0. On the basis of the test results given above and according to Draize Dermal Classification System, the response of CJ304 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:
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: 2946-3750 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 hr
Observation period (in vivo):
1 hr, 24 hr, 48 hr, 72 hr, 7 day and 14 day
Number of animals or in vitro replicates:
three
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
mean of 2 higher reacted ones
Time point:
24/48/72 h
Score:
1.5
Max. score:
2
Reversibility:
fully reversible within: 14 day
Remarks on result:
probability of weak irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
mean of 2 higher reacted ones
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
mean of 2 higher reacted ones
Time point:
24/48/72 h
Score:
2.35
Max. score:
3
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of mild irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
mean of 2 higher reacted ones
Time point:
24/48/72 h
Score:
1.5
Max. score:
2
Reversibility:
fully reversible within: 14 d
Remarks on result:
probability of weak irritation

Table 1. Individual Body Weights and Clinical Observations

Animal ID

Body weight (g)

Body weight change (g)

Clinical observation

D1

D4

D4-D1

7

3750

3772

22

Normal

8

2966

2876

-90

Normal

9

2946

2888

-58

Normal

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

Animal ID

7

8

9

Score on each observation point

1

hr

24

hr

48

hr

72

hr

7

day

1

hr

24

hr

48

hr

72

hr

7

day

14

day

1

hr

24

hr

48

hr

72

hr

7

day

Cornea

Degree of density

0

0

0

0

0

1

2

1

1

0

0

1

2

2

1

0

Area1of opacity

0

0

0

0

0

3

3

1

1

0

0

3

2

1

1

0

Iris

0

02

02

02

02

0

12

02

02

02

02

0

12

02

02

02

Conjunctive

Redness

0

2

1

2

0

2

3

3

3

1

0

2

2

1

2

0

Chemosis

2

1

0

0

0

3

2

2

1

0

0

3

2

1

1

0

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

2: Iris discoloration

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
According to OECD 405 test method, CJ304 showed that a positive irritant to the eye and reversible. Therefore, CJ304 was categorized as irritant to eye (Category 2) based on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315009-IR which is based on the SOP for the OECD 405 (CTPS-TE00441) and OECD 405 (OECD, 2012).There were no effects on mortality.Slight body weight decreased was observed but all animals were clinically normal. Grade 2 corneal opacity in over 50% of area, grade 1 hyperemia of iris and grade 3 diffused redness and eversion of conjunctiva were observed in rabbits during 72 h after dosing.Until D14, all eye irritation effects were not observed. Moreover, iris discoloration was observed.CJ304 was given by a single ocular application at 100 mg amount to NZW 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 articlewas 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 CJ304 was calculated to be 0. On the basis of the test results given above and according to Draize Dermal Classification System, the response of CJ304 was categorized as non-irritant.

 

Eye irritation

There were no effects on mortality. Slight body weight decreased was observed but all animals were clinically normal. Grade 2 corneal opacity in over 50% of area, grade 1 hyperemia of iris and grade 3 diffused redness and eversion of conjunctiva were observed in rabbits during 72 h after dosing.Until D14, all eye irritation effects were not observed. Moreover, iris discoloration was observed.CJ304 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