1-(6-FLUORO-3,4-DIHYDRO-2H-CHROMEN-2-YL)ETHANONE

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-01-17 to 2005-02-10

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: SPL Standard Test Method 595.12

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

limited details on test item, test animals and environmental conditions

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:

1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)ethan-1-one

Cas Number:

620176-90-1

Molecular formula:

C11H11FO2

IUPAC Name:

1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)ethan-1-one

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study reports): JNJ-7928531-AAA (T001481)
- Physical state: liquid
- Appearance: Colourless, light yellow to brown liquid

In vivo test system

Test animals

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: 17 to 20 g (Main Study)
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum):no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS: no data

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

Preliminary Screening Test: 50 and 100% v/v
Main Study: 10%, 25%, and 50 % v/v

No. of animals per dose:

Main Study: 4 per dose

Details on study design:

PRE-SCREEN TESTS:
- Compound solubility: no data
- Irritation: no data
- Systemic toxicity: No signs of systemic toxicity or weight loss at a concentration of 50% v/v in acetone/olive oil 4:1. A weight loss of 2 g was observed with a concentration of 100% v/v.
- Ear thickness measurements: no data
- Erythema scores: no data

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: Stimulation Index of greater than 3.0 indicates a 'positive' result.


TREATMENT PREPARATION AND ADMINISTRATION:
- Three groups, each of four animals, were treated with 50 µL (25 µL per ear) of the test substance as a solution in acetone/olive oil 4:1 at concentrations of 10%, 25%, and 50% v/v. A further group of four animals was treated with acetone/olive oil 4:1 alone.

Positive control substance(s):

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

other: 2,4 Dinitrobenzene sulphonic acid, sodium salt (DNBS) at 1%, 10%, 20% v/v in 1% pluronic L92 in distilled water

Statistics:

no data

Results and discussion

Positive control results:

see: any other information on results (here below)

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1.53

Test group / Remarks:

10% v/v

Results 2

Parameter:

SI

Value:

1.43

Test group / Remarks:

25% v/v

Results 3

Parameter:

SI

Value:

3.54

Test group / Remarks:

50% v/v

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA :
DPM/node obtained by dividing DPM value by 8 (total number of lymph nodes):
Vehicle: 591.85
10% v/v: 904.58
25% v/v: 843.95
50% v/v: 2092.83

DETAILS ON STIMULATION INDEX CALCULATION: see table above

EC3 CALCULATION : The EC3 of the test substance was found to be 43.5%.

CLINICAL OBSERVATIONS: No signs of systemic toxicity were observed in any of the animals tested.

BODY WEIGHTS: no abnormal body weight changes observed in the tested animals

Any other information on results incl. tables

Positive Control Local Lymph Node Assay in the Mouse (2005)

Start Date	Finish Date	Test Material	Concentration	Vehicle	Stimulation Index^a	Classification^b
04/03/2005	10/03/2005	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	acetone/olive oil 4:1	2.76, 3.34, 8.91	Positive
20/04/2005	26/04/2005	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	ethanol/distilled water 7:3	2.64, 8.36, 12.94	Positive
14/07/2005	20/07/2005	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	1% pluronic L92 in distilled water	0.86, 1.50, 6.17	Positive
14/07/2005	20/07/2005	2,4 Dinitrobenzene sulphonic acid, sodium salt (DNBS)	1%, 10%, 20% v/v	1% pluronic L92 in distilled water	1.16, 9.59, 20.71	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:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Since there was indication that the test item elicited a SI ≥ 3 when tested up to 50%, T001481 was considered to be a skin sensitizer. As the EC3 value was > 2% (i.e. 43.5%), the substance is classified as skin sensitizer category 1B according to the criteria of the CLP Regulation (H317).