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Description of key information

The sensitization rate of CJ306 was 100% and CJ306 caused skin 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 May 09, 2016 to September 26, 2016
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 at study initiation: 6-7 weeks
- Weight at study initiation: 351-399g
- Housing: Every two animals were housed in a stainless steel wire mesh cage
- Water: ad libitum
- Acclimation period: 8 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:
0.1mL 10% (w/v) and 0.5mL 50% (w/v) of CJ306 for intradermal and epicutaneous, respectively
Day(s)/duration:
Day 0 and Day 7 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:
0.4 mL 50% (w/v) of CJ306
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)
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%.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1mL 10% (w/v) and 0.5mL 50% (w/v) of CJ306 for intradermal and epicutaneous, respectively. 0.4 mL 50% (w/v) of CJ306 for challenge.
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
Nine treated animals got 1 to 3.
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1mL and 0.5mL WFI (water for injection) for intradermal and epicutaneous, respectively. 0.4 mL 50% (w/v) of CJ306 for challenge.
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
All treated animals got 0.
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
not measured/tested

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

46

1

353

435

Normal

D0-24

47

1

397

463

Normal

D0-24

48

1

385

482

Normal

D0-24

49

1

388

497

Normal

D0-24

50

1

396

431

Normal

D0-24

51

2

384

465

Normal

D0-24

52

2

396

457

Normal

D0-24

53

2

399

492

Normal

D0-24

54

2

371

427

Normal

D0-24

55

2

357

432

Normal

D0-24

56

2

379

448

Normal

D0-24

57

2

372

475

Normal

D0-24

58

2

361

451

Normal

D0-24

59

2

351

435

Normal

D0-24

60

2

357

408

Normal

D0-24

Table 2. Individual Skin Reaction on Induction Sites

Animal#

Group#

Site

Maximum score (Erythema/Edema)

Study Day

1

5

7

12

15

19

46

1

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

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

47

1

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

0/0

0/2

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

48

1

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

0/0

0/0

0/2

0/2

0/2

ID_3

2/2

3/2

4/2

4/2

4/2

4/2

Topical

-

-

2/1

2/2

2/2

2/2

49

1

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

0/0

0/0

0/2

1/2

1/2

ID_3

2/2

3/2

4/2

4/2

4/2

4/2

Topical

-

-

2/1

2/2

2/2

2/2

50

1

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

0/0

0/0

2/2

0/2

1/2

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

51

2

ID_1

2/2

4/2

4/3

4/2

4/2

4/2

ID_2

4/2

0/0

4/3

4/2

4/2

4/2

ID_3

1/NA

4/2

4/3

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

52

2

ID_1

2/2

4/2

4/3

4/2

4/2

4/2

ID_2

4/2

4/2

4/3

4/2

4/2

4/2

ID_3

1/NA

4/2

4/3

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

53

2

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

4/2

2/2

2/2

2/2

0/2

0/2

ID_3

2/NA

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

54

2

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

4/2

4/2

4/2

4/2

4/2

4/2

ID_3

2/NA

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

55

2

ID_1

1/2

4/2

4/2

4/2

4/2

4/2

ID_2

4/2

4/2

4/2

4/2

4/2

4/2

ID_3

1/NA

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

56

2

ID_1

1/2

4/2

4/2

4/2

4/2

4/2

ID_2

4/2

2/2

4/2

4/2

4/2

4/2

ID_3

1/NA

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/3

2/2

57

2

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

4/2

0/2

4/2

4/2

4/2

4/2

ID_3

0/NA

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

58

2

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

4/2

0/2

4/2

4/2

4/2

4/2

ID_3

0/NA

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

59

2

ID_1

2/2

4/2

4/2

4/2

4/2

4/2

ID_2

4/2

0/2

4/2

4/2

4/2

4/2

ID_3

0/NA

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

2/2

60

2

ID_1

1/1

4/2

4/2

4/2

4/2

4/2

ID_2

4/2

0/2

4/2

4/2

4/2

4/2

ID_3

0/NA

4/2

4/2

4/2

4/2

4/2

Topical

-

-

2/2

2/2

2/2

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

46

1

0

0

47

1

0

0

48

1

0

0

49

1

0

0

50

1

0

0

51

2

1

1

52

2

1

2

53

2

2

0

54

2

2

2

55

2

2

2

56

2

3

3

57

2

0

2

58

2

2

2

59

2

0

2

60

2

2

2

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 CJ306 was 100% and CJ306 caused extreme sensitization in guinea pigs. Therefore, CJ306 was categorized as indication of skin sensitising (Category 1).
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315022-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 CJ306 show that test reliability criteria was met.

A 10% and 50% (w/v) CJ306 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) CJ306. 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, 100% treated animals showed sensitization to the CJ306. Under the conditions of this study, CJ306 caused skin sensitization in guinea pigs.

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

Skin sensitization

A 10% and 50% (w/v) CJ306 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) CJ306. 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, 100% treated animals showed sensitization to the CJ306. Under the conditions of this study, CJ306 caused extreme sensitization in guinea pigs.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

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