Octadecanedioic acid, 1,18-dimethyl ester

Endpoint summary

Description of key information

The skin sensitisation potential of the test item octadecanedioic acid, 1,18-dimethyl ester (ODDAME)has been read-across from the substance 9-decenoic acid, methyl ester (9DAME) from the following study:

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). Based on the results of the read across study, a similar result can be expected for the test item.

 

Reference:

* Kreiling, R., Hollnagel, H.M., Hareng, L., Eigler, D., Lee, M.S., Griem, P., Dreesen, B., Kleber, M., Albrecht, A., Garcia, C., Wendel, A., 2008. Comparison of the skin sensitizing potential of unsaturated compounds and assessed by a murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT). Food and Chemical Toxicology 46, 1896-1904.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of 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:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

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.

Reason / purpose for cross-reference:

read-across source

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

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)

Species:

mouse

Strain:

other: CBA/Ca

Sex:

female

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)

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.

Parameter:

SI

Value:

1.61

Remarks on result:

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

Parameter:

SI

Value:

3.02

Remarks on result:

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

Parameter:

SI

Value:

2.42

Remarks on result:

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

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

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:

The skin sensitisation potential of the test item 9-dodecenoic acid, methyl ester (9DDAME) has been read-across from the substance 9-decenoic acid, methyl ester (9DAME) from the following study.

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). Based on the results of the read across study, a similar result can be expected for the test item.

 

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitisation potential of the test item octadecanedioic acid, 1,18-dimethyl ester (ODDAME) has been read-across from the substance 9 -decenoic acid, methyl ester. In a local lymph node assay performed in accordance with OECD Guideline 429, 9-decenoic acid, methyl ester (9-DAME) was found to elicit a borderline response. However, based on the fact that the test material does not contain any structural alerts for reactivity associated with skin sensitisation, the absence of a dose response, and that previously published work indicates that long chain unsaturated fatty acids have the potential to generate false positive results in the LLNA, this result is considered to be a false positive. Therefore, 9-decenoic acid, methyl ester is not considered to be a skin sensitiser. As such, the substance octadecanedioic acid, 1,18-dimethyl ester (ODDAME) is also considered not to be a sensitiser according to Regulation (EC) No. 1272/2008.