Registration Dossier

Administrative data

Description of key information

Skin sensitization

In a Local Lymph Node Assay (LLNA) in mice (CBA/Ca strain) according to OECD Guideline 429, the substance is observed to be sensitising to the skin (Sanders, 2014).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003-09-29 to 2004-09-23
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:
yes
Remarks:
limited details on test item, test animals and environmental conditions
Qualifier:
according to
Guideline:
other: SPL Standard Test method 595.12
GLP compliance:
no
Remarks:
The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme but no formal claim of GLP compliance is made for this study.
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
No further details on test material next to T1036
Species:
mouse
Strain:
CBA/Ca
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS: no data

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data
Vehicle:
dimethyl sulphoxide
Concentration:
10%, 25% and 50% w/w in dimethyl sulphoxide
No. of animals per dose:
Four animals
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: no data
- Irritation: no data
- Lymph node proliferation response: no data
-There were no signs of systemic toxicity following a preliminary sighting test at a concentration of 50%.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: SPL Standard Test Method 595.12
- 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 uL of the test material (25 uL per ear) as asolution in dimethyl sulphoxide at concentrations of 10%, 25% and 50% w/w. A further group of four animals was treated with dimethyl sulphoxide alone.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
no data
Positive control results:
see: any other information on results (here below)
Parameter:
SI
Value:
0.92
Test group / Remarks:
10% w/w group
Parameter:
SI
Value:
1.25
Test group / Remarks:
25% w/w group
Parameter:
SI
Value:
4.05
Test group / Remarks:
50% w/w group
Parameter:
EC3
Value:
40.63
Cellular proliferation data / Observations:
CELLULAR PROLIFERATION DATA
no data

DETAILS ON STIMULATION INDEX CALCULATION
The Stimulation Index (SI) was expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group

EC3 CALCULATION
Using the data generated, an EC3 value of 40.63% was calculated.

CLINICAL OBSERVATIONS:
no signs of systemic toxicity in a preliminary sighting test. No data for the main study

BODY WEIGHTS
no data

Table 1: The Stimulation Index (SI) expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows:

 Concentration (% w/w) in dimethyl sulphoxide  Stimulation Index (SI) b  Result
 10  0.92  Negative
 25  1.25  Negative
 50  4.05  Positive

Using the data generated, an EC3 value of 40.63% was calculated.

b = Test to control ratio greater than 3.0 indicates a ‘positive’ result

Table 2: Positive Control Local Lymph Node Assay in the Mouse (2003)

Start Date

Finish Date

Test Material

Concentration

Vehicle

Stimulation Indexa

Classificationb

13/03/2003

19/03/2003

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

acetone/olive oil 4:1

2.8, 2.3, 5.5

Positive

13/03/2003

19/03/2003

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

acetone/olive oil 4:1

2.0, 1.9, 6.8

Positive

10/10/2003

16/10/2003

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

acetone/olive oil 4:1

1.76, 2.78, 5.06

Positive

16/10/2003

22/10/2003

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

acetone/olive oil 4:1

1.49, 1.73, 5.26

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 material was considered to be a sensitiser under the conditions of the test. Using the data generated, an EC3 value of 40.63% was calculated.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Sanders (2004) investigated the skin sensitization potential of T001036 following topical application to the dorsal surface of the ear of CBA/Ca mice. Primary lymphocyte proliferation was assessed during the sensitizing (induction) phase of the response. Following a preliminary sighting test at which there were no signs of systemic toxicity at a concentration of 50%, three groups, each of four animals, were treated with 50 µL of the test item (25 µL per ear) as a solution in dimethyl sulphoxide at concentrations of 10%, 25% and 50% w/w in dimethyl sulphoxide. A further group of four animals was treated with dimethyl sulphoxide alone. The following stimulation index (SI) values were observed: at 10% concentration: 0.92 (negative result), at 25%: 1.25 (negative result) and at 50%: 4.05 (positive result as test to control ratio was greater than 3.0). Using the data generated, an EC3 value of 40.63% was calculated.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitization

The test item was considered to be a sensitiser under the conditions of the test. Using the data generated, an EC3 value of 40.63% was calculated. Based on these data and the criteria of the CLP Regulation (EC3 value > 2%), the substance is classified as skin sensitizer category 1B (H317: May cause an allergic skin reaction).