2,6,10-trimethylundec-9-enal

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 March 2016 - 12 April 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Principles of method if other than guideline:

There were no deviations from standard operating procedures that affected the integrity of the study.

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

2,6,10-trimethylundec-9-enal

EC Number:

205-460-8

EC Name:

2,6,10-trimethylundec-9-enal

Cas Number:

141-13-9

Molecular formula:

C14H26O

IUPAC Name:

2,6,10-trimethylundec-9-enal

Test material form:

liquid

Specific details on test material used for the study:

Batch SC00016539
Expiry date 18 January 2017

In vivo test system

Test animals

Species:

mouse

Strain:

CBA:J

Remarks:

Mouse, CBA/J strain, inbred, SPF-Quality.

Sex:

female

Details on test animals and environmental conditions:

20 females (nulliparous and non-pregnant), five females per group (main study only).
Young adult animals (approx. 10 weeks old) were selected. Body weight variation was within +/- 20% of the sex mean.

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

test item concentrations of 10, 25 or 50% w/w

No. of animals per dose:

three experimental groups of five female CBA/J mice

Details on study design:

Three consecutive days of treatment, by open application on the ears. Five vehicle control animals were similarly treated, but with the vehicle alone (Acetone/Olive oil (4:1 v/v)). Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of disintegrations per minute (DPM) and a stimulation index (SI) was subsequently calculated for each group.

Positive control substance(s):

not specified

Results and discussion

In vivo (LLNA)

Results

Key result

Parameter:

EC3

Value:

32

Any other information on results incl. tables

The slight erythema of the ears as seen for the animals treated at 25 and 50% and the scaliness as seen for the animals treated at 50% on Day 6 were considered not to have a toxicologically significant effect on the activity of the nodes. The auricular lymph nodes of the animals of the experimental and control groups were considered normal in size, except for the enlarged nodes of one animal treated at 50%. Mean DPM/animal values for the experimental groups treated with test item concentrations 10, 25 and 50% were 773, 1396 and 2459 DPM, respectively. The mean DPM/animal value for the vehicle control group was 569 DPM. The SI values calculated for the test item concentrations 10, 25 and 50% were 1.4, 2.5 and 4.3, 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 32% was calculated.

Applicant's summary and conclusion

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Based on these results according to the recommendations made in the test guidelines, ADOXAL would be regarded as skin sensitizer.

Executive summary:

The study was carried out based on the guidelines described in: EC, No 440/2008; B42: "Skin Sensitization: Local Lymph Node Assay".

Test item concentrations selected for the main study were based on the results of a pre-screen test. In the main study, three experimental groups of five female CBA/J mice were treated with test item concentrations of 10, 25 or 50% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with the vehicle alone (Acetone/Olive oil (4:1 v/v)). Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of disintegrations per minute (DPM) and a stimulation index (SI) was subsequently calculated for each group. The slight erythema of the ears as seen for the animals treated at 25 and 50% and the scaliness as seen for the animals treated at 50% on Day 6 were considered not to have a toxicologically significant effect on the activity of the nodes. The auricular lymph nodes of the animals of the experimental and control groups were considered normal in size, except for the enlarged nodes of one animal treated at 50%. Mean DPM/animal values for the experimental groups treated with test item concentrations 10, 25 and 50% were 773, 1396 and 2459 DPM, respectively. The mean DPM/animal value for the vehicle control group was 569 DPM. The SI values calculated for the test item concentrations 10, 25 and 50% were 1.4, 2.5 and 4.3, 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 32% was calculated.

The six-month reliability check with Alpha-hexylcinnamaldehyde indicates that the Local Lymph Node Assay as performed at WIL Research Europe is an appropriate model for testing for contact hypersensitivity Based on these results and according to the recommendations made in the test guidelines ADOXAL would be regarded as skin sensitizer.