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Description of key information

The skin sensitization potential of T002488 was determined with a Local Lymph Node Assay in the mouse, performed according to the SPL Standard Test Method 595.12. The test substance was deterimined to be not sensitising to the skin under the conditions of the test.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004-11-01 to 2004-12-07
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted following SPL Standard Test method 595.12.
Qualifier:
according to
Guideline:
other: SPL Standard Test Method 595.12
Principles of method if other than guideline:
The assay determines the level of lymphocyte proliferation in lymph nodes draining the application site of the test material. Determination of lymphocyte proliferation is quantified by measuring the incorporation of radiolabeled thymidine in the dividing lymph node cells. The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node (dpm/node) and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).
GLP compliance:
no
Remarks:
The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report had not been audited by the QA Unit. No formal claim of GLP compliance was made for the study.
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Janssen Pharmaceutica N.V.
- Expiration date of the lot/batch: No data
- Purity test date: No data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: No data
- Stability under test conditions: No data


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: No data.

Species:
mouse
Strain:
CBA/Ca
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 15 to 22 grams
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS:
- Temperature (deg C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

Vehicle:
dimethylformamide
Concentration:
vehicle alone, 2.5%, 5% and 10% w/w
No. of animals per dose:
4
Details on study design:
RANGE FINDING TESTS:
- Following a preliminary sighting test, no signs of systemic toxicity were observed at a concentration of 10% w/w.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: a stimulation index of greater than 3.0

TREATMENT PREPARATION AND ADMINISTRATION:
- Three groups, each of four animals were treated with 50 µL (25µuL per ear) of the test substance as a solution in dimethyl formamide at concentrations of 2.5%, 5% and 10% w/w. A further group of four animals was treated with dimethyl formamide alone.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
other: 2,4 Dinitrobenzenesulfonic acid, sodium salt at 1%, 10%, 20% v/v in 1% pluronic F-68 in distilled water
Statistics:
No statistical analysis was used.
Positive control results:
see tables below
Parameter:
SI
Value:
1.81
Test group / Remarks:
4 animals in 2.5% w/w in DMF group
Parameter:
SI
Value:
2.25
Test group / Remarks:
4 animals in 5% w/w in DMF group
Parameter:
SI
Value:
1.91
Test group / Remarks:
4 animals in 10% w/w in DMF group
Cellular proliferation data / Observations:
CELLULAR PROLIFERATION DATA
DPM:
- 2.5% = 11089.82 (1386.23/node)
- 5% = 13787.05 (1723.38/node)
- 10% = 11719.21 (1464.90/node)
- Vehicle Only = 6129.19 (766.15/node)

EC3 CALCULATION
- Not applicable

CLINICAL OBSERVATIONS:
-No mortality or clinical observations were observed.

BODY WEIGHTS:
- No unusualy changes in body weight were observed.

Positive Control Local Lymph Node Assay in the Mouse (2004)

Start Date

Finish Date

Test Material

Concentration

Vehicle

Stimulation Indexa

Classificationb

29/04/2004

05/05/2004

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

acetone/olive oil 4:1

1.40, 2.23, 6.09

Positive

29/04/2004

05/05/2004

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

acetone/olive oil 4:1

1.74, 2.20, 8.89

Positive

14/10/2004

26/10/2004

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

tetrahydrofuran

1.97, 3.71, 7.82

Positive

29/09/2004

05/10/2004

2,4‑Dinitrobenzenesulfonic acid, sodium salt

1%, 10%, 20% v/v

1% pluronic F-68

in distilled water

1.03, 4.41, 13.55

Positive

27/10/2004

02/11/2004

α‑Hexylcinnamaldehyde, tech., 85%

10%, 25%, 50% v/v

cottonseed oil

1.52, 2.63, 5.07

Positive

 


a=        Ratio of test to control lymphocyte proliferation

b=        Stimulation index greater than 3.0 indicates a positive result

* =        Standard Test Method 595 (Pooled nodes)

·=        Standard Test Method 599 (Individual nodes)

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was considered to be a non-sensitiser under the conditions of the test.
Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Following a preliminary sighting test, at which there were no signs of systemic toxicity at a concentration of 10% w/w, three groups, each of four animals, were treated with 50 µl (25 µl per ear) of the test material as a solution in dimethyl formamide at concentrations of 2.5%, 5% and 10% w/w. A further group of four animals was treated with dimethyl formamide alone.

The maximal simulation index (2.25) was obtained for the intermediate concentration tested on mice, equaling 5% w/w in dimethyl formamide.

Given these results, the substance T002488 was not considered to be a skin sensitiser under the conditions of the test.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results of the skin sensitisation test and the criteria given in the CLP regulation, the test item should not be classified as skin sensitiser.