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Administrative data

Description of key information

The sensitization rate of CJ313 was 30% and CJ313 causedmoderatesensitization in guinea pigs (OECD TG406).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 25, 2016 to March 30, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The guinea pig maximization test (GPMT) is already available for the registration outside of EU. Therefore, LLNA is not conducted.
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
- Source: National Laboratory Animal Center, Taipei, Taiwan
- Age: approximately 5 to 6 weeks
- Weight at study initiation: 300-361 g
- Housing: Every two animals were housed in a stainless steel wire mesh cage
- Acclimation period: 7 days
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 50 ± 20%
- Photoperiod: 12-hrs dark / 12-hrs light
Route:
intradermal and epicutaneous
Vehicle:
water
Remarks:
water for injection (WFI)
Concentration / amount:
0.1 mL 10 % (w/v) and 0.4 mL 25 % (w/v) of CJ313 for intradermal and epicutaneous, respectively
Day(s)/duration:
D0 and D7 for intradermal and epicutaneous, respectively
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
water for injection (WFI)
Concentration / amount:
0.2 mL 2.5 % (w/v) of CJ313
Day(s)/duration:
D21
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
For Control group: five
For Treated group: ten
Positive control substance(s):
yes
Remarks:
α-Hexylcinnamaldehyde (HCA)
Positive control results:
The latest results showed that positive control animals had shown maximum skin reactions of 2 and the sensitization rate of α-Hexylcinnamaldehyde (HCA) was 60%.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.4 mL
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The skin sensitizing potential of the test article was evaluated according to the reactions observed in each control and treated animal. Since the score=1 was seen in control animals, sensitizing score >1 in the treated animals represented sensitization.
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.4 mL
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
The skin sensitizing potential of the test article was evaluated according to the reactions observed in each control and treated animal. Since the score=1 was seen in control animals, sensitizing score >1 in the treated animals represented sensitization.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.4 mL of 25%(w/v) CJ313
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
The skin sensitizing potential of the test article was evaluated according to the reactions observed in each control and treated animal. Since the score=1 was seen in control animals, sensitizing score >1 in the treated animals represented sensitization.
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.4 mL of 25%(w/v) CJ313
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
The skin sensitizing potential of the test article was evaluated according to the reactions observed in each control and treated animal. Since the score=1 was seen in control animals, sensitizing score >1 in the treated animals represented sensitization.
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
not measured/tested
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
not measured/tested

Group #1: Control group

Group #2: Treated group

 

Table 1. Individual Body Weight and Clinical Observations

Animal#

Group #

Body Weight (g)

Observation

Day 0

Day 24

D0-24

16

1

324

464

Normal

17

1

318

464

Normal

18

1

352

462

Normal

19

1

361

465

Normal

20

1

342

455

Normal

21

2

310

427

Normal

22

2

342

440

Normal

23

2

308

427

Normal

24

2

346

464

Normal

25

2

333

449

Normal

26

2

330

415

Normal

27

2

339

470

Normal

28

2

325

442

Normal

29

2

300

380

Normal

30

2

333

452

Normal

Table 2. Individual Skin Reaction on Induction Sites

Animal#

Group #

Site

Maximum score (Erythema / Edema)

Study Day

3

7

10

14

17

21

24

16

1

ID_1

0 / 1

2 / 3

2 / 2

4 / 4

4 / 4

4 / 4

4 / 3

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

2 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 3

Topical

-

-

2 / 1

2 / 1

2 / 2

2 / 2

2 / 2

17

1

ID_1

0 / 1

2 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 3

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

2 / 3

3 / 3

4 / 4

4 / 4

4 / 4

4 / 3

Topical

-

-

2 / 1

2 / 1

2 / 2

2 / 2

2 / 2

18

1

ID_1

0 / 1

2 / 3

2 / 2

4 / 4

4 / 4

4 / 4

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 3

2 / 2

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 1

2 / 2

2 / 2

2 / 2

2 / 2

19

1

ID_1

0 / 1

2 / 3

3 / 3

4 / 4

4 / 4

4 / 3

4 / 3

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

2 / 3

2 / 3

4 / 4

4 / 4

4 / 3

4 / 3

Topical

-

-

2 / 1

2 / 1

2 / 2

2 / 2

2 / 3

20

1

ID_1

0 / 1

2 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 3

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 3

Topical

-

-

1 / 1

1 / 1

2 / 2

2 / 2

2 / 2

21

2

ID_1

0 / 1

3 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 4

3 / 4

4 / 4

4 / 4

4 / 3

4 / 4

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 3

22

2

ID_1

0 / 1

2 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 1

2 / 2

2 / 2

2 / 2

2 / 3

23

2

ID_1

0 / 1

3 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 1

2 / 1

2 / 3

2 / 3

2 / 3

24

2

ID_1

0 / 0

3 / 3

3 / 3

4 / 4

4 / 4

4 / 4

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

2 / 3

2 / 3

4 / 4

2 / 3

4 / 3

4 / 4

Topical

-

-

2 / 1

2 / 1

2 / 2

2 / 3

2 / 3

25

2

ID_1

2 / 2

3 / 3

3 / 3

4 / 4

4 / 4

4 / 4

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 4

3 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 1

2 / 1

2 / 2

2 / 3

2 / 3

26

2

ID_1

1 / 2

3 / 3

2 / 2

4 / 4

4 / 4

4 / 4

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 3

3 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 1

2 / 2

2 / 3

2 / 3

2 / 3

27

2

ID_1

0 / 1

3 / 3

3 / 3

4 / 4

4 / 4

4 / 4

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 4

2 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 1

2 / 1

2 / 3

2 / 3

2 / 3

28

2

ID_1

0 / 1

2 / 2

2 / 2

4 / 4

4 / 4 

4 / 4

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 0

3 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 3

2 / 3

29

2

ID_1

0 / 1

2 / 3

2 / 2

4 / 4

4 / 3

4 / 4

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

2 / 3

3 / 4

4 / 4

4 / 4

4 / 4

4 / 3

Topical

-

-

2 / 1

2 / 1

2 / 2

2 / 2

2 / 3

30

2

ID_1

0 / 1

2 / 3

2 / 2

4 / 4

4 / 4

4 / 4

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 1

2 / 1

2 / 2

2 / 3

2 / 2

Table 3. Individual Sensitization Observation

Animal#

Group #

Score

24h

48h

16

1

0

1

17

1

1

1

18

1

0

0

19

1

1

0

20

1

1

0

21

2

1

1

22

2

2

1

23

2

2

1

24

2

1

1

25

2

1

2

26

2

1

1

27

2

1

1

28

2

0

0

29

2

0

0

30

2

0

0

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
According to OECD 406 test method and “Magnusson and Kligman Maximization Grading”, the sensitization rate of CJ313 was 30% and CJ313 caused moderate sensitization in guinea pigs. Therefore, CJ313 was category 1 based on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65316012-IR which is based on the SOP for the OECD 406 (CTPS-TE00516) and OECD 406 (OECD, 1992). The results of this OECD 406 test for CJ313 show that test reliability criteria was met.

A 10% and 25% CJ313 was used for intradermal injection and occlusively patched, respectively, to ten test guinea pigs to induce sensitization. The water for injection was used for similar injection and occlusively patched to five control guinea pigs. Following a recovery period, animals received a challenge patch with 2.5% CJ313. The skin sensitization reactions were scored at approximately 24 and 48 hours after patch removal. At the end of study, body weight increase was observed in all animals. During 48 hours after challenge exposure, 30% treated animals showed sensitization to the CJ313. Under the conditions of this study, CJ313 caused moderate sensitization in guinea pigs.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Skin sensitization

A 10% and 25% CJ313 was used for intradermal injection and occlusively patched, respectively, to ten test guinea pigs to induce sensitization. The water for injection was used for similar injection and occlusively patched to five control guinea pigs. Following a recovery period, animals received a challenge patch with 2.5% CJ313. The skin sensitization reactions were scored at approximately 24 and 48 hours after patch removal. At the end of study, body weight increase was observed in all animals. During 48 hours after challenge exposure, 30% treated animals showed sensitization to the CJ313. Under the conditions of this study, CJ313 caused moderate sensitization in guinea pigs.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification