2-(tetrahydro-5-methyl-5-vinyl-2-furyl)propan-2-ol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientific paper conducted on a group on radical Intermediates of Linalyl Hydroperoxide.

Data source

Reference

Reference Type:

publication

Title:

Skin Sensitization to Linalyl Hydroperoxide: Support for Radical Intermediates

Author:

Michael Bezard,† Ann-Therese Karlberg,‡ Johan Montelius,‡ and Jean-Pierre Lepoittevin*,†

Year:

1997

Bibliographic source:

Chem. Res. Toxicol. 1997, 10, 987-993

Materials and methods

Principles of method if other than guideline:

The LLNA was carried out as essentially recommended by Kimber and Basketter (12). Female mice (CBA/Ca strain, 6-10 weeks old), in groups of four, received 25 íL of the test chemical dissolved in dimethylformamide (DMF) on the dorsum of both ears for 3 consecutive days.

GLP compliance:

no

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Linalool oxide

EC Number:

215-723-9

EC Name:

Linalool oxide

Cas Number:

1365-19-1

IUPAC Name:

2-(5-methyl-5-vinyltetrahydrofuran-2-yl)propan-2-ol

Constituent 2

Reference substance name:

Furan 5

IUPAC Name:

Furan 5

Test material form:

gas under pressure: refrigerated liquefied gas

Details on test material:

Furan and pyran derivatives were prepared according to the literature (21) by epoxidation of linalool with m-CPBA at 0 °C for 4 h (Scheme 3). Furan derivatives 5a,b were predominantly formed (79% yield).

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

The LLNA was carried out as essentially recommended by Kimber and Basketter (12). Female mice (CBA/Ca strain, 6-10 weeks old), in groups of four, received 25 íL of the test chemical dissolved in dimethylformamide (DMF) on the dorsum of both ears for 3 consecutive days. Test solutions were made fresh each day and applied within 30 min. Compounds 1-6 were tested in three different concentrations: 1%, 3%, and 9% (w/w), respectively. Control mice were treated with an equal volume of DMF alone. Five days after the first treatment, all mice were injected intravenously through the tail vein with 20 íCi of [3H]thymidine (specific activity 2 Ci/mmol; Amersham International, Amersham, U.K.) in 250 íL of phosphate-buffered saline. After 5 h,
the mice were sacrificed, the draining auricular lymph nodes were excised and pooled for each group, and a single-cell suspension of lymph node cells was prepared. After washing and precipitation with trichloroacetic acid, thymidine incorporation was determined by â-scintillation counting (13).

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

1, 3, 9

No. of animals per dose:

4 females

Details on study design:

The LLNA was carried out as essentially recommended by Kimber and Basketter (12). Female mice (CBA/Ca strain, 6-10 weeks old), in groups of four, received 25 íL of the test chemical dissolved in dimethylformamide (DMF) on the dorsum of both ears for 3 consecutive days. Test solutions were made fresh each day and applied within 30 min. Compounds 1-6 were tested in three different concentrations: 1%, 3%, and 9% (w/w), respectively. Control mice were treated with an equal volume of DMF alone. Five days after the first treatment, all mice were injected intravenously through the tail vein with 20 íCi of [3H]thymidine (specific activity 2 Ci/mmol; Amersham International, Amersham, U.K.) in 250 íL of phosphate-buffered saline. After 5 h,
the mice were sacrificed, the draining auricular lymph nodes were excised and pooled for each group, and a single-cell suspension of lymph node cells was prepared. After washing and precipitation with trichloroacetic acid, thymidine incorporation was determined by â-scintillation counting (13).

Results and discussion

Positive control results:

These results, coming from a combination of chemicaltrapping experiments and in vivo experimental sensitization data, are in favor of the formation of a carboncentered reactive radical as an intermediate in the skin sensitization to linalyl hydroperoxide.

Any other information on results incl. tables

chemical                     concn (w/w, %)       [3H]thymidine incorpn (dpm/node)       stimulation index

Linalool Oxide              1.0                             139                                                        1.1             

3.0                             189                                                        1.4

9.0                             279                                                        2.1

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Linalool oxide is not a skin sensitiser.