(3H)-benzofuran-2-one

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-08-11 to 2004-10-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

(3H)-benzofuran-2-one

EC Number:

209-052-0

EC Name:

(3H)-benzofuran-2-one

Cas Number:

553-86-6

Molecular formula:

C8H6O2

IUPAC Name:

2,3-dihydro-1-benzofuran-2-one

Details on test material:

- Name of test material (as cited in study report): 2-Coumaranone
- Physical state: solid
- Analytical purity: 99.9 %
- Lot/batch No.: 01V1264/38
- Expiration date of the lot/batch: 2005-06-21
- Storage condition of test material: At room temperature in the dark

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

In the main study, three groups of five experimental animals were epidermally exposed to a 5%, 25% and 50% concentration. Based on the results, two additional groups of animals were treated similarly with test substance concentrations of 0.25 and 1 %.

No. of animals per dose:

5

Positive control substance(s):

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

Results and discussion

Positive control results:

1. 0% (vehicle control) / DPM: 241 / SI: 1.0
2. 5% test substance / DPM: 235 / SI: 1.0
3. 10% test substance / DPM: 766 / SI: 3.2
4. 25% test substance / DPM: 1708 / SI: 7.1

EC3: 9.5%

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

2.8

Test group / Remarks:

Test concentration: 0.25

Results 2

Parameter:

SI

Value:

7.8

Test group / Remarks:

Test concentration: 1.0

Results 3

Parameter:

SI

Value:

19

Test group / Remarks:

Test concentration: 5.0

Results 4

Parameter:

SI

Value:

42

Test group / Remarks:

Test concentration: 25.0

Results 5

Parameter:

SI

Value:

24.9

Test group / Remarks:

Test concentration: 50.0

Results 6

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Test concentrations: 0.0 / 0.25 / 1.0 / 5.0 / 25.0 / 50.0 DPM: 244 or 268 / 743 / 2092 / 4637 / 10256 / 6077

Results 7

Parameter:

EC3

Value:

0.3

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information

Conclusions:

Based on these results 2-Coumaranone should be considered to be a skin sensitiser.

Executive summary:

The study was carried out based on the guidelines described in: OECD, Section 4, Health Effects, No.429 (2002).

Test substance concentrations selected for the main study were based on the results of a preliminary study. In the main study, three groups of five experimental animals were epidermally exposed to a 5%, 25% and 50% concentration respectively on three consecutive days. Five vehicle control animals were similarly treated, but with vehicle alone (N.N-dimethylformamide). Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised. After precipitating the DNA of the lymph node cells, radioactivity measurements were done. Based on the results, two additional groups of animals were treated similarly with test substance concentrations of 0.25 and 1 %. Five vehicle control animals were treated with vehicle alone (N.N-dimethylformamide).

All nodes of the control groups and the majority of nodes of the 0.25 and 1% groups were considered normal in size. The largest nodes were found in the higher dose groups. No other macroscopic abnormalities of the nodes were noted. Mean DPM/animal values for the experimental groups treated with test substance concentrations 5, 25 and 50% were 4637, 10256 and 6077 respectively. The mean DPM/animal value for the vehicle control group was 244. In order to achieve more information regarding the Sl=3 value, additional groups of animals were with a 0.25 and 1% test substance concentration respectively and mean DPM/animal values of 743 and 2092 were calculated. A mean DPM/animal value of 268 was calculated for the vehicle control group. The SI values calculated for the substance concentrations 0.25, 1, 5, 25 and 50% were 2.8, 7.8, 19.0, 42.0 and 24.9 respectively. These data showed a dose-response and an EC3 value of 0.3% was calculated using linear interpolation.

Based on these results 2-Coumaranone should be considered to be a skin sensitiser.