3,7-dimethylnona-1,6-dien-3-ol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

3,7-dimethylnona-1,6-dien-3-ol

EC Number:

233-732-6

EC Name:

3,7-dimethylnona-1,6-dien-3-ol

Cas Number:

10339-55-6

Molecular formula:

C11H20O

IUPAC Name:

3,7-dimethylnona-1,6-dien-3-ol

Details on test material:

- Purity: >97%

Specific details on test material used for the study:

purity 98.1%

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
-Source: Envigo RMS B.V., Inc
- Age at study initiation:
pre-test: 11 - 12 weeks
main study: 7 - 11 weeks

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

25, 50 and 100 %

No. of animals per dose:

5

Details on study design:

Three groups each of five female mice were treated with different concentrations of the test item by topical application at the dorsum of each ear once daily each on three consecutive days. A control group of five mice was treated with the vehicle only. Five days after the first topical
application, the mice were intravenously injected into a tail vein with radio-labelled thymidine (3H-methyl thymidine; 3HTdR). Approximately five
hours after intravenous injection, the mice were sacrificed and the draining auricular lymph nodes were excised and pooled per animal. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes, which were subsequently washed and incubated with trichloroacetic
acid overnight. The proliferative capacity of pooled lymph node cells were then determined by the incorporation of 3H-methyl thymidine
measured in a β-scintillation counter.

Statistics:

All calculations conducted on the DPM values and the ear weights were performed with a validated test script of “R”, a language and environment for statistical computing and graphics.

Results and discussion

Positive control results:

The sensitivity and reliability of the experimental technique employed was assessed by use of α-hexyl cinnamaldehyde dissolved in acetone/olive oil (4+1 v/v) (compound listed in OECD 429 Guideline) which is known to have skin sensitisation properties in mice. The periodic positive control experiment was performed using CBA/CaOlaHsd mice in April 2016.
Results:
10 % α-hexyl cinnamaldehyde dissolved in acetone/olive oil (4+1 v/v): SI = 2.79
25 % α-hexyl cinnamaldehyde dissolved in acetone/olive oil (4+1 v/v) : SI = 7.84
EC3 = 10.6% (w/v)

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

vehicle control group (DMF)

Results 2

Key result

Parameter:

SI

Value:

1.7

Test group / Remarks:

25 % Ethyllinalool

Results 3

Key result

Parameter:

SI

Value:

3.1

Test group / Remarks:

50 % Ethyllinalool

Results 4

Key result

Parameter:

SI

Value:

4

Test group / Remarks:

100 % Ethyllinalool

Results 5

Key result

Parameter:

other: desintegration per minute (DPM)

Value:

6 099.5

Test group / Remarks:

mean DPM per animal; SD 1132.8

Any other information on results incl. tables

EC3 = 48.2 % (w/v)

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

The test item Ethyllinalool was found to be a skin sensitizer and an EC3 value of 48.2 % (w/v) was derived.

Executive summary:

In the study, the test item Ethyllinalool formulated in water-free dimethylformamide (DMF) was assessed for its possible skin sensitising potential. For this purpose a local lymph node assay was performed using test item concentrations of 25, 50, and 100 % (w/v). Clinical signs in the main experiment included squinted or closed eyes, mainly up to 1 h after application, as well as a very mild to moderate (score 1 -2) erythema of the ear skin, and scaly ears in all animals. A statistically significant or biologically relevant increase in ear weights was not observed in any dose group.

In this study Stimulation Indices (S.I.) of 1.7, 3.1, and 4.0 were determined with the test item at concentrations of 25, 50, and 100% in water-free DMF, respectively. A clear dose-response was observed.

The test item Ethylliinalool was found to be a skin sensitiser and an EC3 value of 48.2 % (w/v) was derived.