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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 April 8, 2016 to August 16, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

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 at study initiation: 5-6 weeks
- Weight at study initiation: 300-327g
- Housing: Every two animals were housed in a stainless steel wire mesh cage
- Water: ad libitum
- 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 For Injection (WFI)
Concentration / amount:
0.1mL of 10% (w/v) and 0.5 mL 50% (w/v) CJ302 for intradermal and epicutaneous, respectively
Day(s)/duration:
Day 0 and Day 7 for intraderma 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:
0.4 mL of 50% (w/v) CJ302
Day(s)/duration:
Day 21
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Control group: Five
Treated group: Ten
Positive control substance(s):
yes
Remarks:
HCA (CAS No. 101-86-0)

Results and discussion

Positive control results:
The latest results showed that positive control animals had shown maximum skin reactions of 3 and the sensitization rate of HCA (CAS No. 101-86-0) was 80%.

In vivo (non-LLNA)

Results
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0.4 mL 50% (w/v) CJ302
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
nine treated animals got scores 1 to 3

Any other information on results incl. tables

In the table, Group#1 and Group#2 were control group and treated group, respectively.

 

Table 1. Individual Body Weights and Clinical Observations

Animal#

Group#

Study Day

Observation

Days Seen

0

24

16

1

305

451

Normal

D0-24

17

1

320

450

Normal

D0-24

18

1

313

418

Normal

D0-24

19

1

310

455

Normal

D0-24

20

1

300

393

Normal

D0-24

21

2

320

423

Normal

D0-24

22

2

307

372

Normal

D0-24

23

2

317

441

Normal

D0-24

24

2

324

424

Normal

D0-24

25

2

324

418

Normal

D0-24

26

2

327

424

Normal

D0-24

27

2

320

382

Normal

D0-24

28

2

320

410

Normal

D0-24

29

2

316

405

Normal

D0-24

30

2

326

415

Normal

D0-24

 

Table 2. Individual Skin Reaction on Induction Sites

Animal#

Group#

Site

Maximum score (Erythema/Edema)

Study Day

2

5

7

12

15

19

16

1

ID_1

2/2

4/2

4/2

4/2

4/3

4/2

ID_2

0/0

0/0

0/0

0/0

0/0

0/0

ID_3

2/2

4/2

4/2

4/2

4/3

4/2

Topical

-

-

-

2/2

2/3

2/2

17

1

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

0/0

0/0

0/0

2/2

0/0

ID_3

2/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

-

2/2

2/2

2/2

18

1

ID_1

2/2

4/2

4/2

4/2

4/3

4/2

ID_2

0/0

0/0

0/0

0/0

2/3

0/0

ID_3

2/2

4/2

4/2

4/2

4/3

4/2

Topical

-

-

-

2/2

2/3

2/2

19

1

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

0/0

0/0

0/0

2/2

0/0

ID_3

2/2

3/2

4/2

4/2

4/2

4/2

Topical

-

-

-

2/2

2/2

2/2

20

1

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

0/0

0/0

0/0

2/2

0/0

ID_3

2/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

-

2/2

2/2

2/2

21

2

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

0/0

0/0

0/0

3/2

0/0

ID_3

NA/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

-

NA/2

3/2

2/2

22

2

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

0/0

0/0

0/0

3/2

0/0

ID_3

NA/2

4/2

4/2

4/2

4/2

4/2

Topical

-

-

-

NA/2

3/2

2/2

23

2

ID_1

2/2

3/2

4/2

4/2

4/3

4/2

ID_2

0/0

0/0

0/0

0/0

2/3

0/0

ID_3

NA/2

3/2

4/2

4/2

4/3

4/2

Topical

-

-

-

NA/2

2/3

2/2

24

2

ID_1

2/2

4/2

4/2

4/2

4/3

4/2

ID_2

0/0

0/0

0/0

0/0

2/3

0/0

ID_3

NA/2

4/2

4/2

4/2

4/3

4/2

Topical

-

-

-

NA/2

2/3

2/2

25

2

ID_1

2/2

4/2

4/2

4/2

4/4

4/2

ID_2

0/0

0/0

0/0

0/0

2/4

0/0

ID_3

NA/2

4/2

4/2

4/2

4/4

4/2

Topical

-

-

-

NA/2

2/4

2/2

26

2

ID_1

2/2

3/2

4/2

4/2

4/3

4/2

ID_2

0/0

0/0

0/0

0/0

3/3

0/0

ID_3

NA/2

4/2

4/2

4/2

4/3

4/2

Topical

-

-

-

NA/2

3/3

2/2

27

2

ID_1

2/2

3/2

4/2

4/2

4/3

4/2

ID_2

0/0

0/0

0/0

0/0

3/3

0/0

ID_3

NA/2

4/2

4/2

4/2

4/3

4/2

Topical

-

-

-

NA/2

4/3

2/2

28

2

ID_1

2/2

3/2

4/2

4/2

4/4

4/2

ID_2

0/0

0/0

0/0

0/0

2/4

0/0

ID_3

NA/2

4/2

4/2

4/2

4/4

4/2

Topical

-

-

-

NA/2

2/4

2/2

29

2

ID_1

2/2

4/2

4/2

4/2

4/4

4/2

ID_2

0/0

0/0

0/0

0/0

2/4

0/0

ID_3

NA/2

4/2

4/2

4/2

4/4

4/2

Topical

-

-

-

NA/2

2/4

2/2

30

2

ID_1

2/2

3/2

4/2

4/2

4/4

4/2

ID_2

0/0

0/0

0/0

0/0

2/4

0/0

ID_3

NA/2

4/2

4/2

4/2

4/4

4/2

Topical

-

-

-

NA/2

2/4

2/2

-: no observation was conducted

NA: the site could not be observed because test article stain

 

Table 3. Individual Sensitization Observation  

Animal#

Group#

Score

24h

48h

16

1

0

0

17

1

0

0

18

1

0

0

19

1

0

0

20

1

0

0

21

2

0

0

22

2

2

2

23

2

0

1

24

2

0

1

25

2

2

2

26

2

2

3

27

2

2

1

28

2

0

1

29

2

1

2

30

2

2

3

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 Grsding, the sensitization rate of CJ302 was 90% and CJ302 caused sensitization in guinea pigs. Therefore, CJ302 was categorized as skin sensitising (Category 1) based on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315020-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 CJ302 show that test reliability criteria was met.

A 10% and 50% (w/v) CJ302 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 50% (w/v) CJ302. The skin sensitization reactions were scored at approximately 24 and 48 hours after patch removal. No test article-related adverse systemic effects were observed clinically in surviving animals during the study period. At the end of study, body weight increase was observed in all surviving animals. During 48 hours after challenge exposure, 90% treated animals showed sensitization to the CJ302. Under the conditions of this study, CJ302 caused extreme sensitization in guinea pigs.