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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A Local Lymph Node Assay (LLNA) was performed with the test substance in CBA/J mice according to the OECD Guideline 429. The test substance contained besides 75% ethyl linoleate also 10% ethyl oleate (FA 18:1) as impurity.
Three experimental groups of five female/J mice were treated with test substance concentrations of 25, 50 and 100% w/w on three consecutive days by open application on the ears. Five vehicle control animals were similarly treated, but with vehicle alone (Acetone/Olive oil (4:1 v/v)). Slight irritation of the ear skin and increased sizes of the uricular lymph nodes were observed by most animals treated at 50 and 100%. The ear thickness was not measured. The SI values calculated for the substance concentrations 25, 50 and 100% were 2.3, 6.6 and 8.2, respectively.

However, these test results cannot be interpreted for the following reasons as skin sensitizing effects:
First, the OECD guideline No. 429 states that "despite the advantages of the LLNA over traditional guinea pig test, it should be recognized that there are certain limitations that may necessitate the use of traditional guinea pig tests (e.g., false negative findings in the LLNA with certain metals, false positive findings with certain skin irritants)".
Furthermore previous experiments indicated that chemicals with unsaturated carbon-carbon double bonds may result in a higher number of unspecific, i.e. false positive, results in the LLNA compared to GPMT" (Kreiling 2008).
The skin sensitization potential of eight unsaturated and one saturated lipid (bio)chemicals (oleic acid, linoleic acid, linolenic acid, undecylenic acid, maleic acid, squalene, octinol, fumaric acid, succinic acid) was tested in both the LLNA and the GPMT to address the above-metionned hypothesis (Kreiling, 2008).
Seven out of nine substances were tested positive in the LLNA (oleic acid, linoleic acid, linolenic acid, undecylenic acid, maleic acid, squalene and octinol) and thus would require labelling as skin sensitizers. Fumaric acid and succinic acid tested negative in the LLNA (Kreiling, 2008). In the GPMT reproducible skin reactions indicating an allergic response were only found for undecylenic acid. The result for linoleic acid was inconclusive, while the other seven substances were tested negative for skin sensitization in this assay. For linoleic acid, two animals showed a skin reaction at the 24-h reading, but not after 48 and 72h, suggesting a non-specific rather than an allergic reaction in these animals. This view was supported by the fact that one control animal also showed a skin reaction at the 48-h reading. Another test animal showed a skin reaction at 48 and 72h. Unfortunately, for technical reasons, a re-challenge experiment could not be performed with linoleic acid, so that the nature of the skin reactions observed in the treatment group could not be clarified (Kreiling 2008).

Based on these results, only undecylenic acid would have to be classified and labelled as skin sensitizer according to the European Dangerous Substance Directive (67/548/EEC). The results for linoleic acid were inconclusive, while the other seven substances would not require labelling. Possible mechanisms for unspecific skin cell stimulation and lymph node responses were discussed. In conclusion, the suitability of the LLNA for unsaturated compounds bearing structural similarity to the tested substances should be carefully considered and the GPMT was recommended as an accepted test method for skin sensitization hazard identification.

Methyl linoleate (CAS# 112-63-0) was used as a structural analogue (read across) substance for skin sensitization hazard identification of fatty acids, safflower-oil, Et esters (CAS# 91051-53-5). It can be expected that methyl linoleate would exert similar characteristics in pathophysiologicalmechanism of skin sensitization. Upon activity of dermal esterases, methyl linoleate would be cleaved into linoleic acid and methanol, representing sufficient similarity to the metabolites linoleic acid and ethanol, which result from the cleavage of fatty acids, safflower-oil, Et esters (CAS# 91051-53-5).

A Buehler test was performed with the read-across substance methyl linoleate (CAS# 112-63-0) according to OECD guideline 406. Groups of 10 Dunkin-Hartley guinea pigs were treated with the test substance in concentrations of 40% for topical induction and 20% for topical challenge diluted in olive oil.
All test animals and negative control animals were without any distinct dermal effects after challenge. No deaths occurred and no significant differences in the gain of the body weight occurred. All tested animals, negative control animals and additional animals receiving only treatment with olive oil (vehicle control group) showed weak to moderate dermal reactions. Thus, it was concluded that the test substance itself was a non-sensitizer on the skin of guinea pigs under the given test conditions.

Ethyl linoleate, which is the active ingredient in Fatty acids, safflower-oil, Et esters, is broadly used in leave-on cosmetics, like facial moisturizer/treatment, anti-aging, moisturizer, styling gel/lotion, conditioner, facial cleanser, after shave, hair spray, sunscreen-moisturizer and shaving cream (source:www.cosmeticsdatabase.com).

According to the ECETOC Monograph 32 (2002) on the Use of Human Data in Hazard Classification for Irritation and Sensitization, “no classification with R43 is necessary, where a significant number of individuals (e.g. 100,000) have frequent (daily) skin exposure for at least one year and if there is a system in place to pick up complaints and adverse reaction reports, and where no or only a few isolated cases of allergic contact dermatitis are observed.”

Based on the fact that an eminent number of persons have daily contact with leave-on cosmetic substances containing ethyl linoleate and at the same time there were no clinical case reports on the sensitization potential of these substances available, a sensitization potential of the test item appears very unlikely.

 

Literature:

- Kreiling 2008: Comparison of the skin sensitizing potential of unsaturated compounds as assessed by the murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT), Food and Chemical Toxicology 46 (2008) 1896-1904.

- www.cosmeticsdatabase.com

- ECETOC Monograph 32 (2002), Use of Human Data in Hazard Classification for Irritation and Sensitization.


Migrated from Short description of key information:
RA: 112-63-0: GPMT (methyl linoleate): not sensitising
LLNA: sensitising (BASF, 2010)

Justification for selection of skin sensitisation endpoint:
Reliable GLP and guideline compliant study with minor deviations. Methyl linoleate (CAS# 112-63-0) was used as a structural analogue (read-across) substance for skin sensitization hazard identification of Fatty acids, safflower-oil, Et esters. It can be expected that methyl linoleate would exert similar characteristics in pathophysiological mechanism of skin sensitization. Upon activity of dermal esterases, methyl linoleate would be cleaved into linoleic acid and methanol, representing sufficient similarity to the metabolites linoleic acid and ethanol, resulting from cleavage of fatty acids, safflower-oil, Et esters.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available data is considered reliable and suitable for classification purposes under 67/548/EEC. As a result, the substance does not need to be classified and labelled as skin sensitizer under Directive 67/548/EEC, as amended for the 31st time in Directive2009/2/EC.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result, the substance does not need to be classified and labelled as skin sensitising under Regulation (EC) No 1272/2008, as amended for the fifth time in Directive EC 944/2013.

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