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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 October 31, 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

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
- Source: National Laboratory Animal Center, Taipei, Taiwan
- Age: approximately 5 to 7 weeks
- Weight at study initiation: 323-397 g
- Housing: Every two animals were housed in a stainless steel wire mesh cage
- Acclimation period: 8 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 for injection (WFI)
Concentration / amount:
0.1m L 3% and 0.4mL 50% of CJ305 for intradermal and epicutaneous, respectively
Day(s)/duration:
Day0 and Day 7 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:
0.2mL 2.5% of CJ305
Day(s)/duration:
Day 21
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
For control group: five
For treated group: twelve
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)

Results
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0.2 mL 2.5% of CJ305
No. with + reactions:
2
Total no. in group:
11
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

343

455

Normal

02

1

357

467

Normal

03

1

371

416

Normal

04

1

337

405

Normal

05

1

334

420

Normal

06

2

334

419

Normal

07

2

333

416

Normal

08

2

369

467

Normal

09

2

349

434

Normal

10

2

427

-

D0-2 Normal

D3 Labor breath with some yellow-colored nasal discharge. Lateral recumbency in the cage. Cynosis.

D4 Found dead

11

2

365

431

Normal

12

2

369

488

Normal

13

2

335

419

Normal

14

2

323

407

Normal

15

2

333

440

Normal

16

2

371

507

Normal

17

2

397

461

Normal

#10 was found dead on D4.

 

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

0/2

4/2

4/3

4/3

4/2

4/2

4/2

ID_2

0/0

2/2

2/3

2/3

2/3

2/2

2/2

ID_3

0/2

4/3

4/3

4/3

4/2

4/2

4/2

Topical

-

-

2/3

2/3

2/2

2/2

2/2

02

1

ID_1

0/2

4/2

4/3

4/3

4/2

4/2

4/2

ID_2

0/0

2/2

2/3

2/3

2/2

2/2

2/2

ID_3

3/2

4/3

4/3

4/3

4/2

4/2

4/2

Topical

-

-

2/3

2/3

2/2

2/2

2/2

03

1

ID_1

0/2

4/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

2/2

2/2

2/2

2/2

2/2

2/2

ID_3

0/2

4/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

2/2

04

1

ID_1

0/2

4/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

2/2

2/2

2/2

2/2

2/2

2/2

ID_3

3/2

4/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

2/2

05

1

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

2/2

2/2

2/2

2/2

2/2

2/2

ID_3

3/2

4/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

2/2

06

2

ID_1

0/2

4/2

4/3

4/3

4/2

4/2

4/2

ID_2

0/0

2/2

2/2

2/2

2/2

2/2

2/2

ID_3

0/2

4/2

4/3

4/2

4/2

4/2

4/2

Topical

-

-

2/3

2/3

2/2

2/2

2/2

07

2

ID_1

0/2

4/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

2/2

NA/NA

2/2

2/2

2/2

2/2

ID_3

0/2

4/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/3

2/3

2/2

2/2

2/2

08

2

ID_1

0/2

4/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

2/2

NA/NA

2/2

2/2

2/2

2/2

ID_3

0/2

4/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

2/2

09

2

ID_1

0/2

4/2

4/2

4/2

3/2

3/2

4/2

ID_2

0/0

2/2

2/2

2/2

2/2

2/2

2/2

ID_3

0/2

4/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

2/2

10

2

ID_1

0/0

-

-

-

-

-

-

ID_2

0/0

-

-

-

-

-

-

ID_3

0/1

-

-

-

-

-

-

Topical

-

-

-

-

-

-

-

11

2

ID_1

0/2

4/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

2/2

NA/2

2/2

2/2

2/2

2/2

ID_3

0/2

4/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

NA/2

2/2

2/2

2/2

2/2

12

2

ID_1

0/2

4/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

2/2

NA/2

2/2

2/2

2/2

2/2

ID_3

0/2

4/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

1/2

1/2

2/2

2/2

2/2

13

2

ID_1

0/2

4/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

0/2

1/2

2/2

2/2

2/2

2/2

ID_3

0/2

4/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

1/2

1/2

2/2

2/2

2/2

14

2

ID_1

0/2

4/2

4/2

4/2

4/3

4/3

4/2

ID_2

0/0

2/2

NA/2

2/2

2/2

2/2

2/2

ID_3

3/2

4/2

4/2

4/2

4/3

4/3

4/2

Topical

-

-

NA/2

2/2

2/3

2/3

2/2

15

2

ID_1

0/2

4/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

2/2

NA/2

2/2

2/2

2/2

2/2

ID_3

0/2

4/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

NA/2

2/2

2/2

2/2

2/2

16

2

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

-

ID_2

1/0

0/0

2/2

2/2

2/2

2/2

-

ID_3

4/2

4/2

4/2

4/2

4/2

4/2

-

Topical

-

-

2/2

2/2

2/2

2/2

-

17

2

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

-

ID_2

1/0

0/0

2/2

2/2

2/2

2/2

-

ID_3

2/2

4/2

4/2

4/2

4/2

4/2

-

Topical

-

-

2/2

2/2

2/2

2/2

-

-: no observation was conducted

 

Table 3. Individual Sensitization Observation

Animal#

Group #

Score

24h

48h

01

1

0

0

02

1

0

0

03

1

0

0

04

1

0

0

05

1

1

0

06

2

1

2

07

2

1

1

08

2

1

1

09

2

1

1

10

2

-

-

11

2

1

1

12

2

1

0

13

2

2

3

14

2

1

1

15

2

1

0

16

2

1

1

17

2

1

1

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 406 test method and “Magnusson and Kligman Maximization Grading”, the sensitization rate of CJ305 was 18% and CJ305 caused mild sensitization in guinea pigs. Therefore, CJ305 was not met classification on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65316010-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 CJ305 show that test reliability criteria was met.

A 3% and 50% CJ305 was used for intradermal injection and occlusively patched, respectively, to 12 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% CJ305. The skin sensitization reactions were scored at approximately 24 and 48 hours after patch removal. One treated animal was found dead on Day 4. The probable cause of death was congenital heart abnormalities and considered to be not test article-related. At the end of study, body weight increase was observed in all surviving animals. During 48 hours after challenge exposure, two of eleven (18%) treated animals showed sensitization to the CJ305. Under the conditions of this study, CJ305 caused mild sensitization in guinea pigs.