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Toxicological information

Skin sensitisation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
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.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

In vivo test system

Test animals

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: 316-384 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

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
water
Remarks:
Water of Injection (WFI)
Concentration / amount:
0.1 mL 4% (w/v) and 0.4 mL 5% (w/v) of CJ308 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
Challenge
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
Water for Injection (WFI)
Concentration / amount:
0.2 mL 2.5% (w/v) of CJ308
Day(s)/duration:
Day21
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
For control group (Group #1): five
For treated group (Group #2): ten
Positive control substance(s):
yes
Remarks:
α-Hexylcinnamaldehyde (HCA)

Results and discussion

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%.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
5 % (w/v)
No. with + reactions:
7
Total no. in group:
9
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
water for injection
No. with + reactions:
0
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

Any other information on results incl. tables

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

357

491

Normal

02

1

345

469

Normal

03

1

316

413

Normal

04

1

349

456

Normal

05

1

362

483

Normal

06

2

332

459

Normal

07

2

351

434

Normal

08

2

325

413

Normal

09

2

319

419

Normal

10

2

343

481

Normal

11

2

373

483

Normal

12

2

324

461

Normal

13

2

342

465

Normal

14

2

350

449

Normal

15

2

384

-

Normal

-: data missing

 

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

1 / 2

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

2 / 3

4 / 4

4 / 4

4 / 4

4 / 3

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 2

02

1

ID_1

0 / 1

2 / 3

3 / 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

2 / 3

4 / 4

4 / 4

4 / 4

4 / 3

Topical

-

-

2 / 2

2 / 3

2 / 2

2 / 3

2 / 2

03

1

ID_1

0 / 1

2 / 3

3 / 4

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 / 4

3 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 3

2 / 3

04

1

ID_1

0 / 1

2 / 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 / 2

3 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 2

2 / 3

2 / 2

2 / 2

2 / 3

05

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

2 / 3

2 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 2

2 / 2

2 / 3

2 / 2

2 / 3

06

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

2 / 3

2 / 3

3 / 4

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 3

07

2

ID_1

0 / 1

4 / 4

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 / 4

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 2

2 / 3

2 / 2

2 / 2

2 / 3

08

2

ID_1

1 / 2

3 / 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

1 / 1

3 / 3

3 / 4

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 2

09

2

ID_1

0 / 1

2 / 3

3 / 3

4 / 4

4 / 4

4 / 3

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

2 / 3

3 / 3

3 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 3

10

2

ID_1

1 / 2

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 / 4

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 3

11

2

ID_1

1 / 1

2 / 3

2 / 3

4 / 4

4 / 4

4 / 3

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 / 3

4 / 4

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 3

12

2

ID_1

0 / 1

3 / 3

2 / 3

4 / 3

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 / 4

4 / 4

Topical

-

-

2 / 2

2 / 1

2 / 3

2 / 3

2 / 3

13

2

ID_1

1 / 1

2 / 3

3 / 3

4 / 3

4 / 4 

4 / 3

4 / 4

ID_2

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

0 / 0

ID_3

1 / 1

3 / 4

3 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 2

2 / 1

2 / 2

2 / 2

2 / 2

14

2

ID_1

1 / 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

3 / 4

3 / 3

3 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 2

2 / 2

2 / 3

2 / 3

2 / 3

15

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 / 3

3 / 3

4 / 4

4 / 4

4 / 4

4 / 4

Topical

-

-

2 / 2

2 / 2

2 / 2

2 / 2

2 / 3

Table 3. Individual Sensitization Observation

Animal#

Group #

Score

24h

48h

01

1

1

0

02

1

1

0

03

1

1

1

04

1

1

0

05

1

1

0

06

2

2

1

07

2

3

3

08

2

2

1

09

2

3

3

10

2

3

2

11

2

2

2

12

2

0

0

13

2

0

0

14

2

2

2

15

2

1

-

-: data missing

Applicant's summary and conclusion

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 CJ308 was 78% and CJ308 caused strong sensitization in guinea pigs. Therefore, CJ308 was classed as category 1 based on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65316011-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 CJ308 show that test reliability criteria was met.

A 4% and 5% CJ308 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% CJ308. 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, 78% treated animals showed sensitization to the CJ308. Under the conditions of this study, CJ308 caused strong sensitization in guinea pigs.