1,1'-Biphenyl, 4-methyl-4'-(3E)-3-penten-1-yl-

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-08-12 to 2006-09-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

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:

-

EC Number:

473-310-0

EC Name:

-

Cas Number:

478385-88-5

Molecular formula:

C18H20

IUPAC Name:

4-methyl-4'-[(3E)-pent-3-en-1-yl]-1,1'-biphenyl

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan NetherlandsB.V. Postbus 6174NL
- 5960 AD Horst / The Netherlands
- Age at study initiation: 8 - 12 weeks (beginning of treatment)
- Weight at study initiation: 22 +/- 1.5 g
- Housing: single
- Diet: ad libitum; pelleted standard diet
- Water: ad libitum
- Acclimation period: At least 5 days prior to the start of dosing under test conditions after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: °C 22 +/- 3
- Humidity: 30-82 %
- Air changes: not specified
Photoperiod: 6 a.m. - 6 p.m.

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

5, 10, 25 wt. %

No. of animals per dose:

Total 16 animals:
3 test groups with 4 animals
1 control group with 4 animals

Details on study design:

according to guideline

Positive control substance(s):

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

Statistics:

The mean values and standard deviations were calculated in the body weight tables. The ANOVA (Dunnett-test) was conducted to assess whether the difference is statistically significant between test item groups and negative control (vehicle) group. Statistical significance was at the five per cent level (p < 0.05). However, both biological and statistical significance were considered together.

Results and discussion

Positive control results:

Based on the results obtained with the positive control, the study can be considered to be valid.

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

1.38

Test group / Remarks:

Test Group (5%)

Results 2

Key result

Parameter:

SI

Value:

1.62

Test group / Remarks:

Test Grouip (10%)

Results 3

Key result

Parameter:

SI

Value:

1.23

Test group / Remarks:

Test Group (25 %)

Cellular proliferation data / Observations:

EC3 CALCULATION
All SI values are below 3, thus there was no calculation of the EC3 value.

CLINICAL OBSERVATIONS:
No clinical signs have been observed. No mortality was reported.

BODY WEIGHTS
Body weight development was without any abnormalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material was found to be not a skin sensitiser under the described conditions.

Executive summary:

The purpose of this Local Lymph Node assay was to identify the contact allergenic potential of the test material when administered to the dorsum of both ear lobes of mice. This study should provide a rational basis for risk assessment to the sensitising potential of the test item in man. In order to study a possible allergenic potential of the test material, three groups each of four female mice were treated with different concentrations of the test item dissolved in acetone/olive oil (4:1) by topical application at the dorsum of each ear lobe (left and right) on three consecutive days. A control group of four 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). Approximately five hours after intravenous injection, the mice were sacrificed and the draining auricular lymph nodes excised and pooled per group. 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 was determined by the incorporation of 3H-methyl thymidine measured in a beta-scintillation counter.

The animals did not show any clinical signs during the course of the study and no cases of mortality were observed.

In this study Stimulation Indices (SI) of 1.38, 1.62 and 1.23 were determined with the test item at concentrations of 5, 10 and 25% (w/v) in acetone/olive oil (4/1), respectively.

In conclusion, the test material was not a skin sensitiser in this assay.