Registration Dossier

Administrative data

Description of key 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.

RA 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:
April 13 - June 08, 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands B.V. Postbus 6174 NL - 5960 AD Horst
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 20.1 +/- 1.6 g
- Housing: single
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2°C
- Humidity (%): 45-65%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: day 1 To: day 6
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:
RANGE FINDING TESTS:
- Compound solubility: 25 and 50 %
- Irritation: No
- Lymph node proliferation response: -

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: OECD 429
- Criteria used to consider a positive response: Stimulation index > 3

TREATMENT PREPARATION AND ADMINISTRATION:
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
Standard statistical methods have been applied for data processing.
Positive control results:
Conc. SI
0%: 1.00
5% 1.78
10% 2.54
25% 4.88
Key result
Parameter:
SI
Value:
1.26
Test group / Remarks:
Test Group: 10%
Key result
Parameter:
SI
Value:
0.91
Test group / Remarks:
Test Group: 25%
Key result
Parameter:
SI
Value:
0.65
Test group / Remarks:
Test Group: 50%
Cellular proliferation data / Observations:
CELLULAR PROLIFERATION DATA
Test item concentration DPM per lymph node
Vehicle 822.9
10% 1034.8
25% 751.3
50% 535.8

EC3 CALCULATION : Could not be calculated, since all S.I.s are below 3.

CLINICAL OBSERVATIONS: No deaths occurred during the study period. No symptoms of local toxicity at the ears of the animals and no systemic findings 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 item was not a skin sensitiser under the test conditions of this study.
Executive summary:

Objective

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 ears of mice.

This study should provide a rational basis for risk assessment to the sensitising potential of the test item in man.

Study Design

In order to study a possible allergenic potential of the test material, 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 (left and right) 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). 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 determined by the incorporation

of 3H-methyl thymidine measured in a beta-scintillation counter.

Results

The animals did not show any signs of local irritation or systemic toxicity during the course of the study and no cases of mortality were observed.

In this study Stimulation Indices (S.I.) of 1.26, 0.91, and 0.65 were determined with the test item at concentrations of 10, 25, and 50% in acetone:olive oil (4+1), respectively.

Conclusion

The test item 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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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:
read-across source
Key result
Parameter:
SI
Value:
1.26
Test group / Remarks:
Test Group: 10 %
Key result
Parameter:
SI
Value:
0.91
Test group / Remarks:
Test Group: 25 %
Key result
Parameter:
SI
Value:
0.65
Test group / Remarks:
Test Group: 50 %
Interpretation of results:
GHS criteria not met
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 there is no need for classification according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures.