Registration Dossier

Administrative data

Description of key information

Skin sensitisation:

In a LLNA test performed according to SPL Standard Test Method 595.12, the test item was observed to be a skin sensitiser (Sanders, 2004). A K2 score was assigned to this key study.

Skin sensitisation in vitro:

An in vitro or in chemico skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study (initiated before October 11th 2016) is available.

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:
2004-02-02 to 2004-02-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
not specified
Qualifier:
according to
Guideline:
other: SPL Standard Test Method 595.12
Deviations:
not specified
GLP compliance:
no
Remarks:
The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report has not been audited by the QA Unit. No formal claim of GLP compliance is made for this study.
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA/Ca
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS: no data

ENVIRONMENTAL CONDITIONS: no data

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
25% or 50% v/v in acetone/olive oil and 100%
No. of animals per dose:
three groups with four animals in each group
Details on study design:
PRE-SCREEN TESTS:
- Compound solubility: no data
- Irritation: no data
- Systemic toxicity: no signs of systemic toxicity at a concentration of 100%
- Ear thickness measurements: no data
- Erythema scores: no data

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: Test to control ratio greater than 3.0 indicates a ‘positive’ result.

TREATMENT PREPARATION AND ADMINISTRATION:
Three groups, each of four animals, were treated with 50 µL of the undiluted test material (25 µL per ear) or the test material as a solution in acetone/olive oil 4:1 at concentrations of 25% or 50% v/v. A further group of four animals was treated with acetone/olive oil 4:1 alone.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
other: 2,4 Dinitrobenzenesulfonic acid, sodium salt at 1%, 10%, 20% in 1% pluronic F-68 in distilled water
Positive control results:
see: any other information on results (here below)
Parameter:
SI
Value:
1.68
Test group / Remarks:
based on 4 animals of 25% v/v goup in acetone/olive oil 4:1
Parameter:
SI
Value:
4.63
Test group / Remarks:
based on 4 animals of 50% v/v group in acetone/olive oil 4:1
Parameter:
SI
Value:
6.2
Test group / Remarks:
based on 4 animals of 100% group
Cellular proliferation data / Observations:
CELLULAR PROLIFERATION DATA: no data

DETAILS ON STIMULATION INDEX CALCULATION: see results table above

EC3 CALCULATION: Using the data generated, an EC3 value of 36.3% was calculated.

CLINICAL OBSERVATIONS: no data

BODY WEIGHTS: no data

Positive Control Local Lymph Node Assay in the Mouse (2004)

Start Date

Finish Date

Test Material

Concentration

Vehicle

Stimulation Indexa

Classificationb

29/04/2004

05/05/2004

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

acetone/olive oil 4:1

1.40, 2.23, 6.09

Positive

29/04/2004

05/05/2004

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

acetone/olive oil 4:1

1.74, 2.20, 8.89

Positive

14/10/2004

26/10/2004

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

tetrahydrofuran

1.97, 3.71, 7.82

Positive

29/09/2004

05/10/2004

2,4‑Dinitrobenzenesulfonic acid, sodium salt

1%, 10%, 20% v/v

1% pluronic F-68

in distilled water

1.03, 4.41, 13.55

Positive

27/10/2004

02/11/2004

α‑Hexylcinnamaldehyde, tech., 85%

10%, 25%, 50% v/v

cottonseed oil

1.52, 2.63, 5.07

Positive


a=        Ratio of test to control lymphocyte proliferation

b=        Stimulation index greater than 3.0 indicates a positive result

* =        Standard Test Method 595 (Pooled nodes)

·=        Standard Test Method 599 (Individual nodes)

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
The test item was considered to be a sensitiser under the conditions of the test. Based on the calculated EC3 value of 36.3% and the criteria of the CLP Regulation (EC3 value > 2%), the substance is classified as skin sensitiser category 1B (H317).
Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

A local lymph node assay (LLNA) was performed to assess the skin sensitisation potential of the test item in the mouse (CBA/Ca strain). 

Following a preliminary sighting test at which there were no signs of systemic toxicity at a concentration of 100%, three groups, each of four animals, were treated with 50 µl of the undiluted test material (25 µl per ear) or the test material as a solution in acetone/olive oil 4:1 at concentrations of 25% or 50% v/v. A further group of four animals was treated with acetone/olive oil 4:1 alone. The Stimulation Index (SI) for each treatment group was as follows: 1.68 at 25% v/v, 4.63 at 50% v/v and 6.20 at 100%. Using the generated data, an EC3 value of 36.3% was calculated. The test item was considered to be a sensitiser under the conditions of the test.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitisation:

Based on the study results and the criteria of the CLP Regulation, the test item should be classified as skin sensitising substance, category 1B (H317).

Respiratory sensitisation:

No data were available to decide on the classification for respiratory sensitisation.