Registration Dossier

Administrative data

Description of key information

The sensitization rate of CJ321 was 0% and CJ321 caused weak sensitization 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 December 23, 2016 to March 30, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
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: 314-407 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
Concentration / amount:
0.1 mL 1 % and 0.4 mL 20% of CJ321 for intradermal and epicutaneous, respectively
Day(s)/duration:
Day0 and Day7 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 of injection (WFI)
Concentration / amount:
0.2 mL 10 % of CJ321
Day(s)/duration:
Day21
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:
48
Group:
test group
Dose level:
10 % of CJ321
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
Water for injection
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
5% HCA
No. with + reactions:
3
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation

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

01

1

377

449

Normal

02

1

407

484

Normal

03

1

361

405

Normal

04

1

387

447

Normal

05

1

370

443

Normal

06

2

407

508

Normal

07

2

383

463

Normal

08

2

391

517

Normal

09

2

374

419

Normal

10

2

340

443

Normal

11

2

314

441

Normal

12

2

345

454

Normal

13

2

326

409

Normal

14

2

396

501

Normal

15

2

390

497

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

01

1

ID_1

2 / 1

3 / 2

4 / 2

4 / 3

4 / 3

4 / 3

4 / 3

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 2

4 / 2

4 / 3

4 / 3

4 / 3

4 / 3

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 2

02

1

ID_1

0 / 1

3 / 2

4 / 2

4 / 3

4 / 3

4 / 3

4 / 3

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 2

4 / 2

4 / 3

4 / 3

4 / 3

4 / 3

Topical

-

-

2 / 2

2 / 3

2 / 2

2 / 2

2 / 2

03

1

ID_1

1 / 1

3 / 2

4 / 3

4 / 3

4 / 4

4 / 2

4 / 2

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

1 / 1

3 / 2

4 / 3

4 / 3

4 / 4

4 / 2

4 / 2

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 2

04

1

ID_1

2 / 1

3 / 2

4 / 3

4 / 3

4 / 3

4 / 2

4 / 2

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 2

4 / 3

4 / 3

4 / 4

4 / 2

4 / 2

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 2

05

1

ID_1

0 / 1

3 / 2

4 / 3

4 / 3

4 / 4

4 / 2

4 / 2

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

0 / 1

3 / 2

4 / 3

4 / 3

4 / 3

4 / 2

4 / 2

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 2

06

2

ID_1

1 / 1

3 / 3

4 / 2

4 / 3

4 / 4

4 / 2

4 / 2

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

3 / 2

3 / 2

4 / 2

4 / 3

4 / 4

4 / 1

4 / 1

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 1

2 / 2

07

2

ID_1

2 / 1

3 / 3

4 / 2

4 / 3

4 / 4

4 / 2

4 / 2

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

3 / 2

3 / 2

4 / 2

4 / 3

4 / 3

4 / 2

4 / 1

Topical

-

-

2 / 2

2 / 2

2 / 3

2 / 2

2 / 2

08

2

ID_1

0 / 1

3 / 2

4 / 3

4 / 3

4 / 3

4 / 2

4 / 2

ID_2

1 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

3 / 2

3 / 2

4 / 3

4 / 3

4 / 3

4 / 1

4 / 1

Topical

-

-

2 / 3

2 / 2

2 / 2

2 / 2

2 / 2

09

2

ID_1

0 / 1

3 / 2

4 / 3

4 / 3

4 / 4

4 / 2

4 / 2

ID_2

1 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

3 / 2

3 / 2

4 / 3

4 / 3

4 / 4

4 / 1

4 / 1

Topical

-

-

2 / 2

2 / 2

2 / 3

2 / 2

2 / 3

10

2

ID_1

1 / 1

3 / 2

4 / 3

4 / 3

4 / 3

4 / 2

4 / 2

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

3 / 2

3 / 2

4 / 3

4 / 3

4 / 3

4 / 2

4 / 2

Topical

-

-

2 / 2

2 / 2

2 / 3

2 / 2

2 / 3

11

2

ID_1

0 / 1

3 / 2

4 / 2

4 / 3

4 / 4

4 / 3

4 / 3

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

2 / 2

3 / 2

4 / 2

4 / 3

4 / 3

4 / 2

4 / 2

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 2

12

2

ID_1

0 / 1

3 / 2

4 / 2

4 / 3

4 / 4

4 / 3

4 / 3

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

3 / 2

3 / 2

4 / 2

4 / 3

4 / 3

4 / 2

4 / 2

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 2

13

2

ID_1

0 / 1

3 / 2

4 / 2

4 / 3

4 / 3 

4 / 3

4 / 3

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

3 / 2

3 / 2

4 / 2

4 / 3

4 / 3

4 / 2

4 / 2

Topical

-

-

2 / 2

2 / 2

2 / 3

2 / 2

2 / 2

14

2

ID_1

0 / 1

3 / 2

4 / 3

4 / 3

4 / 4

4 / 3

4 / 3

ID_2

0 / 0

3 / 1

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

3 / 2

3 / 3

4 / 3

4 / 3

4 / 3

4 / 2

4 / 2

Topical

-

-

2 / 3

2 / 2

2 / 3

2 / 2

2 / 2

15

2

ID_1

0 / 1

3 / 2

4 / 3

4 / 3

4 / 3

4 / 3

4 / 3

ID_2

0 / 0

3 / 1

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

3 / 2

3 / 2

4 / 3

4 / 3

4 / 3

4 / 2

4 / 2

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 2

Table 3. Individual Sensitization Observation

Animal#

Group #

Score

24h

48h

01

1

1

1

02

1

1

1

03

1

1

1

04

1

2

1

05

1

0

1

06

2

1

1

07

2

1

1

08

2

0

0

09

2

1

1

10

2

1

1

11

2

1

1

12

2

0

1

13

2

1

0

14

2

1

0

15

2

1

1

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 406 test method and “Magnusson and Kligman Maximization Grading”, the sensitization rate of CJ321 was 0% and CJ321 caused weak sensitization in guinea pigs. Therefore, CJ321 was not met a category based on GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65316013-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 CJ321 show that test reliability criteria was met.

A 1% and 20% CJ321 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 10% CJ321. 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, 0% treated animals showed sensitization to the CJ321. Under the conditions of this study, CJ321 caused weak sensitization in guinea pigs.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

All animals appeared clinically normal throughout the study. The body weights of all animals increased at the end of study.

During the study period, the erythema or edema were observed at three pairs of intradermal injection sites in all animals. This was caused by test article and the expected reaction caused by FCA treatment. After topical induction, the erythema or edema with scores 1 to 3 were also observed at application sites in all animals.

The sensitivity and reliability of GPMT method were assessed by using a positive control, alpha-Hexylcinnamaldehyde (HCA; CAS No. 101-86-0) at Testing Facility. The latest results showed that positive control animals had shown maximum skin reactions of 2 and the sensitization rate of HCA was 60% (Appendix IX). Therefore, the results met the acceptance criteria (a response of at least 30%) and the GPMT method of Testing Facility is a valid method in compliance with OECD #406.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The skin sensitization rate of CJ321 was 0% and CJ321 caused weak sensitization in guinea pigs (OECD TG406).

However, the result has not met a category based on GHS criteria.