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Toxicological information

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:
The study was conducted between 20 December 2016 and 24 January 2017.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
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:
2,6-dimethylhept-5-enal
EC Number:
203-427-2
EC Name:
2,6-dimethylhept-5-enal
Cas Number:
106-72-9
Molecular formula:
C9H16O
IUPAC Name:
2,6-dimethylhept-5-enal
impurity 1
Chemical structure
Reference substance name:
6-methylhept-5-en-2-one
EC Number:
203-816-7
EC Name:
6-methylhept-5-en-2-one
Cas Number:
110-93-0
Molecular formula:
C8H14O
IUPAC Name:
6-methylhept-5-en-2-one
impurity 2
Chemical structure
Reference substance name:
(1R,2R,5R)-2-methyl-5-(prop-1-en-2-yl)cyclopentan-1-ol
Cas Number:
83059-39-6
Molecular formula:
C9H16O
IUPAC Name:
(1R,2R,5R)-2-methyl-5-(prop-1-en-2-yl)cyclopentan-1-ol
impurity 3
Chemical structure
Reference substance name:
(1R,2S,5R)-2-methyl-5-(prop-1-en-2-yl)cyclopentan-1-ol
Cas Number:
83026-65-7
Molecular formula:
C9H16O
IUPAC Name:
(1R,2S,5R)-2-methyl-5-(prop-1-en-2-yl)cyclopentan-1-ol
impurity 4
Reference substance name:
2-(3-methylcyclopent-2-en-1-yl)propan-2-ol
Molecular formula:
C9H16O
IUPAC Name:
2-(3-methylcyclopent-2-en-1-yl)propan-2-ol
Test material form:
liquid
Specific details on test material used for the study:
Identification: Melonal
Appearance: Colourless to pale yellow liquid
Batch: PE0016691

In vitro test system

Details on the study design:
N/A

In chemico test system

Details on the study design:
N/A

In vivo test system

Test animals

Species:
mouse
Strain:
CBA:J
Sex:
female
Details on test animals and environmental conditions:
Mouse, CBA/J strain, inbred, SPF-Quality.
Recognized by the international guidelines as the recommended test system (e.g. OECD, EC, EPA).
Source: Janvier, Le Genest-Saint-Isle, France

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
25, 50 or 100%
No. of animals per dose:
5
Details on study design:
Three groups of five animals were treated with one test item concentration per group. The highest test item concentration was selected from the pre-screen test.
One group of five animals was treated with the vehicle.

Results and discussion

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Value:
2.1
Test group / Remarks:
25% Concentration
Parameter:
SI
Value:
4.6
Test group / Remarks:
50% Concentration
Parameter:
SI
Value:
5.5
Test group / Remarks:
100% Concentration
Key result
Parameter:
EC3
Value:
34

Any other information on results incl. tables

Pre-screen Test

Very slight erythema was noted for the animals treated at 50% and 100% between Day 1 and Day 6.

Variations in ear thickness during the observation period were less than 25% from Day 1 pre-dose values.

Based on these results, the highest test item concentration selected for the main study was a 100% concentration.

Main Study

Skin Reactions / Irritation

The very slight erythema of the ears as shown by several animals treated at 50% and all animals treated at 100% on Days 2 and/or 3 was considered not to have a toxicologically significant effect on the activity of the nodes.

Systemic Toxicity

No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

Macroscopic Examination of the Auricular Lymph Nodes and Surrounding Area

All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size. No macroscopic abnormalities of the surrounding area were noted for any of the animals.

Radioactivity Measurements and SI Values

Mean DPM/animal values for the experimental groups treated with test item concentrations 25, 50 and 100% were 990, 2144 and 2591 DPM, respectively. The mean DPM/animal value for the vehicle control group was 467 DPM. The SI values calculated for the test item concentrations 25, 50 and 100% were 2.1, 4.6 and 5.5, respectively.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
The SI values calculated for the test item concentrations 25, 50 and 100% were 2.1, 4.6 and 5.5, respectively.
These results indicate that the test item could elicit a SI ≥ 3. The data showed a dose-response and an EC3 value (the estimated test item concentration that will give a SI =3) of 34% was calculated.
The six-month reliability check with Alpha-hexylcinnamaldehyde indicates that the Local Lymph Node Assay as performed at Charles River Den Bosch is an appropriate model for testing for contact hypersensitivity (see Appendix 2 of study report).
Executive summary:

The SI values calculated for the test item concentrations 25, 50 and 100% were 2.1, 4.6 and 5.5, respectively.

These results indicate that the test item could elicit a SI ≥ 3. The data showed a dose-response and an EC3 value (the estimated test item concentration that will give a SI =3) of 34% was calculated.

The six-month reliability check with Alpha-hexylcinnamaldehyde indicates that the Local Lymph Node Assay as performed at Charles River Den Bosch is an appropriate model for testing for contact hypersensitivity.