Octadecanedioic acid, 1,18-dimethyl ester

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

10 January 2012 to 24 January 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Read-across from GLP guideline study. Read-across justification: A comparison target substance (9DDAME) and the read-across substance (9DAME) shows that the two substances share structural similarities, increasing from a chain length of C10 to C12 with similar functional groups and also have ‘mechanistic action’ similarities.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection 2011-07-19 to 2011-07-21; Date of signature 2011-08-31

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

methyl 9-decenoate

EC Number:

662-772-0

Cas Number:

25601-41-6

Molecular formula:

C11H20O2

IUPAC Name:

methyl 9-decenoate

Details on test material:

- Name of test material (as cited in study report): 9-decenoic acid, methyl ester (9DAME)
- Physical state: Clear colourless liquid
- Analytical purity: 99%
- Lot/batch No.: 184-109
- Date received: 2011-04-01
- Storage conditions: room temperature in the dark under nitrogen

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/Ca

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

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

Remarks:

This vehicle was chosen as it produced the most suitable formulation at the required concentration.

Concentration:

25%, 50% and 100% v/v in acetone/olive oil 4:1.

No. of animals per dose:

4 animals per dose

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

The stimulation index was 4.05. Therefore, ?-Hexylcinnamaldehyde, tech., 85% was considered to be a sensitiser under the conditions of the test.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1.61

Remarks on result:

other: Concentration (% v/v) in acetone/ olive oil 4:1, 25 %: 1.61

Results 2

Parameter:

SI

Value:

3.02

Remarks on result:

other: Concentration (% v/v) in acetone/ olive oil 4:1, 50 %: 3.02

Results 3

Parameter:

SI

Value:

2.42

Remarks on result:

other: Concentration (% v/v) in acetone/ olive oil 4:1, 100 %: 2.42

Results 4

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

The radioactive disintegrations per minute per lymph node are as follows: - Concentration (% v/v) in acetone/ olive oil 4:1, Vehicle: 12665.97 - Concentration (% v/v) in acetone/ olive oil 4:1, 25 %: 20382.35 - Concentration (% v/v) in acetone/ olive oil 4:1, 50 %: 38258.42 - Concentration (% v/v) in acetone/ olive oil 4:1, 100 %: 30617.01

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item returned a borderline response under the conditions of the test. An expert review of these study results (Basketter, 2012) indicated that 9-decenoic acid, methyl ester (9DAME) does not contain any structural alerts for reactivity associated with skin sensitisation and is a long chain unsaturated fatty acid. Published work has indicated that unsaturated fatty acids have the potential to generate false positive results in the LLNA. Several long chain unsaturated fatty acids, such as oleic acid, have proven to be positive in the LLNA but were clear negatives in guinea pig maximisation test conducted in parallel, an outcome which was consistent with their absence of skin sensitising effects in humans.

Based upon the above considerations, the very borderline nature of the single positive result and the absence of a dose response in this test it is feasible that a false positive result may have been obtained and hence 9-decenoic acid, methyl ester (9DAME) is not considered to be a skin sensitiser.

Executive summary:

A study was performed to assess the skin sensitisation potential of the test item in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear, according to OECD Guideline 429, in compliance with GLP. Three groups, each of four animals, were treated with 50 μL (25 μL per ear) of the undiluted test item (100%) or the test item as a solution in acetone/olive oil 4:1 at concentrations of 50% or 25% v/v. A further group of four animals was treated with acetone/olive oil 4:1 alone. The Stimulation Index expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group were 1.6.1, 3.02 and 2.42 for concentrations of 25%, 50% and 100%, respectively. The test item returned a borderline response under the conditions of
the test. An expert review of these study results (Basketter, 2012) indicated that 9-decenoic acid, methyl ester (9DAME) does not contain any structural alerts for reactivity associated with skin sensitisation and is a long chain unsaturated fatty acid. Published work has indicated that unsaturated fatty acids have the potential to generate false positive results in the LLNA. Several long chain unsaturated fatty acids, such as oleic acid, have proven to be positive in the LLNA but were clear negatives in guinea pig maximisation test conducted in parallel, an outcome which was consistent with their absence of skin sensitising effects in humans. Based upon the above considerations, the very borderline nature of the single positive result and the absence of a dose response in this test it is feasible that a false positive result may have been obtained and hence 9-decenoic acid, methyl ester (9DAME) is not considered to be a skin sensitiser (Harlan Laboratories Ltd, 2012).