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Description of key information

Read Across OECD 429: not sensitizing to skin

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

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

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
For this endpoint a one-to-one read across was performed to a chemical similar compound of the same chemical class with a comparable phys. chem. profile and similar response in biological assays. The relevant study was performed according to GLP and the methods applied are fully compliant with OECD TG 429. A detailed read across justification is provided in chapter 13 of this dossier.
Reason / purpose for cross-reference:
read-across source
Key result
Parameter:
SI
Value:
1.8
Test group / Remarks:
10%
Key result
Parameter:
SI
Value:
1.7
Test group / Remarks:
25%
Key result
Parameter:
SI
Value:
1.3
Test group / Remarks:
50%
Interpretation of results:
GHS criteria not met
Conclusions:
For this endpoint a one-to-one read across was performed to a chemical similar compound of the same chemical class with a comparable phys. chem. profile and similar response in biological assays. The relevant study was performed according to GLP and the methods applied are fully compliant with OECD TG 429. A detailed read across justification is provided in chapter 13 of this dossier. The study for the source compound was performed according to GLP and the methods applied are fully compliant with OECD TG 429. The test material was not a skin sensitiser under the test conditions of this study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the provided information the test item is not classified and labelled for skin sensitization according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures.