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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:
Apr 03 - May 02, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (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

Constituent 1
Chemical structure
Reference substance name:
4-Ethoxy-2,3-difluor-4'-propyl-1,1'-biphenyl
EC Number:
638-734-4
Cas Number:
157248-24-3
Molecular formula:
C₁₇H₁₈F₂O
IUPAC Name:
4-Ethoxy-2,3-difluor-4'-propyl-1,1'-biphenyl
Test material form:
solid: crystalline

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA/CaOlaHsd
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V. Postbus 6174 5960 AD Horst / The Netherlands
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: -
- Age at study initiation: 9-10 weeks
- Weight at study initiation: (21.5 +/- 1.1) g
- Housing: group
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:
- Indication of any skin lesions:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 45 - 65
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
10, 25, and 50% (w/w)
No. of animals per dose:
5
Details on study design:
According to guideline
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
one-way ANOVA

Results and discussion

Positive control results:
5% SI=1.6
10% SI=2.4
25% SI=5.9

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
1.6
Test group / Remarks:
10% Test group
Key result
Parameter:
SI
Value:
1.7
Test group / Remarks:
25% Test group
Key result
Parameter:
SI
Value:
1.3
Test group / Remarks:
50% Test group
Cellular proliferation data / Observations:
CELLULAR PROLIFERATION DATA

DETAILS ON STIMULATION INDEX CALCULATION

Group DPM SI
BG: 290.9 1.0
10% 508.9 1.8
25% 484.9 1.7
50% 378.5 1.3

EC3 CALCULATION
No EC3 calculation as all SIs are below 3.

CLINICAL OBSERVATIONS:
No deaths occurred during the study period.
No symptoms of local skin irritation at the ears of the animals and no signs of systemic toxicity were observed during the study period.

BODY WEIGHTS
The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material was not a skin sensitiser under the test conditions of this study.
Executive summary:

The purpose of this Local Lymph Node Assay was to assess the skin sensitizing potential of the test material when administered to the dorsum of both ears of mice.
This study should provide a rational basis for risk assessment to the sensitizing potential of the test item in man.

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 429. In order to study a possible skin sensitizing potential of the test material, three groups each of five female mice were treated with different concentrations (10, 25 and 50%) 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 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 was then determined by the incorporation of 3H-methyl thymidine measured in a β-scintillation counter.

The animals did not show any signs of systemic toxicity or local skin irritation during the course of the study and no cases of mortality were observed. A statistically significant or biologically relevant increase in ear thickness values was not observed in any of the treatment groups in comparison to the vehicle group.
In this study Stimulation Indices (S.I.) of 1.8, 1.7 and 1.3 were determined with the test item at concentrations of 10, 25, and 50% (w/w) in acetone/olive oil 4/1 (v/v), respectively.

The test material was not a skin sensitiser under the test conditions of this study.