6-Fluoro-3-(piperidin-4-yl)benz[d]isoxazole 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:

other: 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

Qualifier:

no guideline followed

Principles of method if other than guideline:

SPL Standard Test Method 595.12:
The test is designed to assess the skin sensitising potential (delayed type hypersensitivity) of the test material following topical application to the dorsal surface of the ear. Primary lymphocyte proliferation is assessed during the sensitising (induction) phase of the response.

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

Reference

Name:

Unnamed

Type:

Constituent

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):

not specified

Results and discussion

In vivo (LLNA)

Results

Results 1

Key result

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

The Stimulation Index (SI) is expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group.

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).