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Toxicological information

Skin sensitisation

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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

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.