6-fluoro-3-(piperidin-4-yl)-1,2-benzoxazole hydrochloride

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2003-05-19 to 2003-06-16

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The study was conducted following SPL Standard Test method 595.12.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: SPL Standard Test method 595.12.

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

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 has not been audited by the QA unit. No formal claim of GLP compliance is made for this study.

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

6-FLUORO-3-(PIPERIDIN-4-YL)-1,2-BENZOXAZOLE HYDROCHLORIDE

EC Number:

700-303-4

Cas Number:

84163-13-3

Molecular formula:

C12H13FN2O.HCl

IUPAC Name:

6-FLUORO-3-(PIPERIDIN-4-YL)-1,2-BENZOXAZOLE HYDROCHLORIDE

Test material form:

solid: particulate/powder

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/Ca

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS: no data

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: 2003-05-19 to 2003-06-16

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

25µL per ear at concentration 0, 2.5, 5, and 10% w/w

No. of animals per dose:

4

Details on study design:

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 radiolabelled thymidine in the dividing lymph node cells.

RANGE FINDING TESTS:
- Compound solubility: no data
- Irritation: Following preliminary sighting tests at which there were no deaths or signs of systemic toxicity at concentrations of 5% and 10%
- Lymph node proliferation response: 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).


MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: Stimulation Index greater than 3.


TREATMENT PREPARATION AND ADMINISTRATION:
- Three groups, each of four animals, were treated with 50 µl of the test material (25 µl per ear) as a suspension 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):

other: see attached file

Results and discussion

Positive control results:

See Any other information on results incl. tables

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1.46

Test group / Remarks:

2.5%

Results 2

Parameter:

SI

Value:

1.35

Test group / Remarks:

5%

Results 3

Parameter:

SI

Value:

1.36

Test group / Remarks:

10%

Any other information on results incl. tables

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

Project Number	Start Date	Finish Date	Test Material	Concentration	Vehicle	Stimulation Index^a	Classification^b
039/687·	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
039/688*	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
039/719*	14/10/2004	26/10/2004	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	tetrahydrofuran	1.97, 3.71, 7.82	Positive
039/720*	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
039/723*	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)

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material (RT 001492) was considered to be a non-sensitiser under the conditions of the test. The test material did not meet the criteria for classification as a sensitiser according to EU labelling regulations Commission Directive 2001/59/EC. No symbol and risk phrase are required.
Applying the criteria laid down in Regulation (EC) No 1272/2008 the test material (RT 001492) does not require classification as a skin sensitiser (Stimulation index <3).