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Description of key information

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:
1991-01-29 to 1991-02-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to outdated OECD Guideline 406.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study performed prior to availability of LLNA methodology.
Species:
guinea pig
Strain:
other: Bor:DHPW
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen/Kreis Paderborn
- Age at study initiation: 5-7 weeks
- Weight at study initiation: mean of 356 g (315-393 g)
- Housing: 5 animals per cage (Makrolon-cages type IV)
- Diet (e.g. ad libitum): Altromin 3020 pellets ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): ca. 50 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
polyethylene glycol
Concentration / amount:
Intradermal induction: 5 % (w/v)
Topical induction: 25 % (w/v)
Challenge: 25 % (w/v)
[25% is the maximum concentration that can be formulated]
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
Intradermal induction: 5 % (w/v)
Topical induction: 25 % (w/v)
Challenge: 25 % (w/v)
[25% is the maximum concentration that can be formulated]
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS:
- Concentrations: 3, 6, 12 and 25 % (w/v)
- Test animals: 4

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: Intradermal -, topical induction 48 h
- Test groups: 1
- Control group: 1
- Site: dorso-cranial, -medial and -caudal
- Frequency of applications: Intradermal once initially, topical induction once after 7 d
- Duration: 7 d
- Concentrations: 5 % (w/v) for interdermal and 25 % (w/v) for topical

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21 d after topical intradermal induction
- Exposure period: 24 h
- Test groups: 1
- Control group: 1
- Site: Left flank for test substance application and right flank for negative control
- Concentrations: 25 % (w/v)
- Evaluation (hr after challenge): 48 and 72 h
Challenge controls:
10 negative control animals
Positive control substance(s):
no
Hours after challenge:
48
Group:
test chemical
Dose level:
25 % (w/v)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: . Hours after challenge: 48.0. Group: test group. Dose level: 25 % (w/v). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Hours after challenge:
72
Group:
test chemical
Dose level:
25 % (w/v)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: . Hours after challenge: 72.0. Group: test group. Dose level: 25 % (w/v). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Hours after challenge:
48
Group:
negative control
Dose level:
25 % (w/v)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: . Hours after challenge: 48.0. Group: negative control. Dose level: 25 % (w/v). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Hours after challenge:
72
Group:
negative control
Dose level:
25 % (w/v)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: . Hours after challenge: 72.0. Group: negative control. Dose level: 25 % (w/v). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

No symptoms and no mortalities occurred during the treatment. The gain in weight of the test group was equal to the control group. No skin reactions occurred during the experiment.

The clinical findings for the pilot study for the topical induction having applied test formulations of 3, 6, 12 to a maximum of 25 % are given below. The pilot studies of the same design for finding the application concentration for the challenge yielded exactly the same results for animals 41 to 45.

Erythema and edema:

Animal

3 %

6 %

12 %

25 %

48 h

72 h

48 h

72 h

48 h

72 h

48 h

72 h

2

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

4

0

0

0

0

0

0

0

0

5

0

0

0

0

0

0

0

0

The clinical findings for the challenge after 48 and 72 h having applied a 25 % (w/v) test formulation are given below.

Erythema and edema:

Animal

Control group

Test substance patch

Control patch

48 h

72 h

48 h

72 h

1

0

0

0

0

2

0

0

0

0

3

0

0

0

0

4

0

0

0

0

5

0

0

0

0

6

0

0

0

0

7

0

0

0

0

8

0

0

0

0

9

0

0

0

0

10

0

0

0

0

Test substance group

21

0

0

0

0

22

0

0

0

0

23

0

0

0

0

24

0

0

0

0

25

0

0

0

0

26

0

0

0

0

27

0

0

0

0

28

0

0

0

0

29

0

0

0

0

30

0

0

0

0

31

0

0

0

0

32

0

0

0

0

33

0

0

0

0

34

0

0

0

0

35

0

0

0

0

36

0

0

0

0

37

0

0

0

0

38

0

0

0

0

39

0

0

0

0

40

0

0

0

0

Bodyweights of animals of the control and test substance group on day 0 and 24 are given below.

Control group

Test substance group

Animal

bw [g] on

day 0

bw [g] on

Day 24

Animal

bw [g] on

day 0

bw [g] on

Day 24

1

315

481

21

318

467

2

339

482

22

338

580

3

334

523

23

391

495

4

332

489

24

365

535

5

359

501

25

390

489

6

335

461

26

338

488

7

347

491

27

375

545

8

343

483

28

353

497

9

363

518

29

385

533

10

368

535

30

364

556

11

357

529

31

337

465

12

333

483

32

372

514

13

367

503

33

352

485

14

365

516

34

357

471

15

369

517

35

372

534

16

316

498

36

360

550

17

367

533

37

345

490

18

357

547

38

388

579

19

378

565

39

367

539

20

354

529

40

393

549

Mean

350

509

Mean

363

518

S

18

26

S

21

36

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
After challenge with a 25 % formulation of the test item no skin reactions occurred, neither in the test nor in the control group. The test substance is considered not sensitising to the skin.
Executive summary:

In a GLP-compliant dermal sensitisation study according to OECD guideline 406 with TCD-emulsifier (25 % w/v in polyethylene glycol E400), 20 male young adult guinea pigs (strain: Bor:DHPW) were tested using the method of Magnusson and Kligman (GPMT). No mortalities or clinical symptoms were observed. A 25 % solution of the test item (the maximum attainable concentration for formulations) did not cause primary irritation. Therefore, animals were treated with sodium lauryl sulfate (SLS) prior to topical application of the test item to induce skin irritation.

The animals of the test group were exposed intradermally (5 % w/v) to the test substance, followed by a single topical exposure (25 % w/v) after 7 days. The topical challenge (25 % w/v) was conducted 21 days after the initial intradermal induction for 24 h. Observations were made after 48 and 72 h.  None of the exposed animals showed signs of an allergic reaction.

In this study, the test item is not a dermal sensitiser according to Regulation (EC) 1272/2008.

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

In a GLP compliant dermal sensitization study according to OECD guideline 406 with TCD-emulsifier (25 % w/v) in polyethylene glycol E400, 20 male young adult guinea pigs (strain: Bor:DHPW) were tested using the method of Magnusson and Kligman (GPMT). No mortalities or clinical symptoms were observed. A 25 % solution of the test item (the maximum attainable concentration in formulations) did not cause primary irritation. Therefore, animals were treated with sodium lauryl sulfate (SLS) prior to topical application of the test item to induce skin irritation.

The animals of the test group were exposed intradermally (5 % w/v) to the test substance, followed by a single topical exposure (25 % w/v) after 7 days. The topical challenge (25 % w/v) was conducted 21 days after the initial intradermal induction for 24 h. Observations were made after 48 and 72 h. None of the exposed animals showed signs of an allergic reaction.


Migrated from Short description of key information:
Negative guinea pig maximization test (Magnusson and Kligman) under GLP.

Justification for selection of skin sensitisation endpoint:
GLP guideline study

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In a reliable GLP OECD 406 study, the test substance did not show any sensitizing potential. Classification is not warranted.