Tris{4-[(4-acetylphenyl)sulfanyl]phenyl}sulfonium hexafluorophosphate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

hexafluoro-λ⁵-phosphanuide; tris({4-[(4-acetylphenyl)sulfanyl]phenyl})sulfanium

EC Number:

700-373-6

Cas Number:

953084-13-4

Molecular formula:

C42 H33 O3 S4 . F6 P

IUPAC Name:

hexafluoro-λ⁵-phosphanuide; tris({4-[(4-acetylphenyl)sulfanyl]phenyl})sulfanium

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sulzfeld
- Age at study initiation: 8 – 12 weeks
- Weight at study initiation: 19.1 g – 21.2 g
- Housing: single housed
- Diet (e.g. ad libitum): Kliba-Labordiät (Maus / Ratte Haltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24
- Humidity (%): 30 – 70
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Study design: in vivo (LLNA)

Vehicle:

propylene glycol

Concentration:

40 % w/w preparation of the test substance in propylene glycol or with the vehicle alone

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: low water solubility
- Irritation: the results of a pretest with a 40% test-substance preparation in propylene glycol were considered, which did not show increased ear weights and lymph node weights as indication of ear irritation.
- Lymph node proliferation response: the results of a pretest with a 40% test-substance preparation in propylene glycol were considered, which did not show increased ear weights and lymph node weights.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: radioactive Murine Local Lymph Node Assay
- Criteria used to consider a positive response: The parameters used to characterize the response are lymph node cell count, 3H-thymidine incorporation into the lymph node cells and to a certain extent lymph node weight. The increase SI of cell count by a factor of ≥ 1.5 and/or of 3H-thymidine incorporation by a factor of ≥ 3 as compared to the concurrent vehicle control group is generally considered as indicating a sensitizing potential of a test substance.

TREATMENT PREPARATION AND ADMINISTRATION:
- Form of application: Epicutaneous application is simulating dermal contact with the compound which is possible to occur under practical use conditions.
Concentration: As the 40 % test-substance preparation was the maximum technically applicable concentration, it was chosen for the main test, which was carried out as a limit test.
- Application volume: 25 μL per ear
- Site of application: Dorsal part of both ears
- Frequency of application: 3 consecutive applications (day 0 – day 2) to the same application site
- ³H-thymidine injection: On study day five (about 66 to 72 hours after the last application of test substance to the ears) the mice were injected intravenously with 20 μCi of 3H-thymidine in 250 μl of sterile saline into a tail vein.
- Terminal procedures: The animals were sacrificed on study day 5 about 5 hours after 3H-thymidine injection by cervical dislocation.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

The positive control induced positive responses in the auricular lymph nodes when applied as 3%, 10% or 30% preparations in acetone or methyl ethyl ketone.
lt is concluded that Alpha-Hexylcinnamaldehyde, techn. 85 % has a sensitizing effect in the Murine Local Lymph Node Assay under the test conditions chosen.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: control:1.00 test: 1.28 Calculation on basis of 4 animals due to irregularities during 3H-thymidine injection.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: control: 1052.1 test: 1343.7, Calculation on basis of 4 animals due to irregularities during 3H-thymidine injection.

Any other information on results incl. tables

Lymph node weight, Cell count, 3H-Thymidine incorporation and Ear weight: Stimulation indices (test group x / test group 1 (vehicle control))

Test group	Treatment	Lymph node Weight Index	Cell Count Index	³H-thymidine inc. [DPM/lymph node pair] Index	Ear Weight Index
1 2*	vehicle propylene glycol 40% in propylene glycol	1.00 1.05	1.00 1.23	1.00 1.28	1.00 0.99

* Calculation on basis of 4 animals due to irregularities during 3H-thymidine injection.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU