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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:

Methyl laurate (CAS No. 111-82-0) was tested for its skin sensitisation potential according to OECD Guideline 406 (Busschers, 1998). 10 Dunkin-Hartley guinea pigs were tested in a Guinea pig maximization test and compared with 5 control animals. 50% dilution of the test substance in corn oil was used for intradermal induction and 100% used for epidermal induction.Challenge treatment was performed by dermal application of the test substance at 20 % in corn oil. 24 and 48 hours after challenge exposure all skin examination scores were zero in all test animals and negative control animals. Based on the study results no classification is required according to EU classification criteria for skin sensitisation.

 

A Guinea Pig Maximisation Test of Skin Sensitization was performed with methyl oleate (CAS No. 112-62-9) according to OECD Guideline 406 (Bien, 1993). 20 male and female Pirbright white guinea pigs were treated with the test substance and compared with 20 negative control animals. The sensitivity of the animal strain was periodically tested using 2,4 dinitrochlorobenzene and benzocaine as positive control substances. A 5% dilution of the test substance in peanut oil was used for intradermal induction and 100% used for epidermal induction of the scapular region on days 1 and 8. 14 days after the last induction treatment, all animals were challenged epicutaneously with the undiluted test liquid test substance. 24 and 48 hours after challenge exposure all skin examination scores were zero in all test animals and negative control animals. Based on the study results no classification is required according to EU classification criteria for skin sensitisation.

Another Guinea Pig Maximisation Test of Skin Sensitization was performed with Fatty acids, C16-18 and C18-unsatd., Me esters (CAS No. 67762-38-3) according to OECD Guideline 406 (Bien, 1993). 20 male and female Pirbright white guinea pigs were treated with the test substance and compared with 20 negative control animals. The sensitivity of the animal strain was periodically tested using 2,4 dinitrochlorobenzene and benzocaine as positive control substances. A 5% dilution of the test substance in peanut oil was used for intradermal induction symmetrically in two rows on either side of the spine on day 1 and 100% used for epidermal induction of the trunk region on day 7. 14 days after the last induction treatment, all animals were challenged for 24 hours epicutaneously with the undiluted test liquid test substance under occlusive conditions. 24 and 48 hours after challenge exposure all skin examination scores were zero in all 20 test animals and 20 negative control animals. Based on the study results no classification is required according to EU classification criteria for skin sensitisation.

A Buehler Test on Skin Sensitization was performed with methyl hexanoate (CAS No. 106-70-7) according to OECD Guideline 406 (Pittermann, 1992). Ten Crl:(HA)BR guinea pigs were treated with the test substance and compared with ten negative control animals. The sensitivity of the animal strain was periodically tested. In preliminary studies a 90% dilution of the test substance in olive oil was found to be the minimal irritating concentration and a 50% dilution to be the maximally non-irritating test substance concentration. Three epidermal inductions were performed with 90 % test substance diluted in olive oil in weekly intervals using a patch test chamber for 6 hours under occlusive conditions. 14 days after the last induction treatment, all animals were challenged for 6 hours epicutaneously with 50% test substance diluted in olive oil under occlusive conditions. 24 hours after challenge exposure one test animal and three negative control animals showed skin reactions. 48 hours after challenge exposure three out of ten test animals and three out of 10 negative control animals showed skin reactions, indicating that the test substance was slightly irritating, but not sensitising to skin under the given conditions. Based on the study results no classification is required according to EU classification criteria for skin sensitisation.

Another Buehler Test on Skin Sensitization was performed with methyl linoleate (CAS No. 112-63-0) according to OECD Guideline 406 (Pittermann, 1992). Ten Dunkin-Hartley guinea pigs were treated with the test substance and compared with ten negative control animals. Additionally ten vehicle control animals were treated with olive oil only in parallel to the induction and challenge treatment of the other two animal groups. The sensitivity of the animal strain was periodically tested. In preliminary studies a 40% dilution of the test substance in olive oil was found to be the minimal irritating concentration and a 20% dilution to be the maximally non-irritating test substance concentration. Three epidermal inductions were performed with 40 % test substance diluted in olive oil in weekly intervals using a patch test chamber for 6 hours under occlusive conditions. 14 days after the last induction treatment, all animals of the test and negative control groups were challenged for 6 hours epicutaneously with 20% test substance diluted in olive oil under occlusive conditions. The second control group was treated with olive oil alone. All tested animals, negative control animals and animals receiving only treatment with olive oil (vehicle control group) showed weak to moderate dermal reactions. Thus, the test substance itself was proven to be a non-sensitizer on the skin of guinea pigs. Based on the study results no classification is required according to EU classification criteria for skin sensitisation.

Taken together, all available experimental animal data indicate that members of the category. fatty acid methyl esters have no skin sensitisation potential.

 

Additionally, the OASIS Database provided from the Danish Environmental Protection Agency and Danish QSAR group, National Food Institute, Technical University of Denmark (DTU) was used to assess the sensitization potential of fatty acid methyl esters by QSAR prediction. The following members were all predicted to have no skin sensitization potential:

 

- Methyl hexanoate (C6, CAS No. 106-70-7)

- Methyl octanoate (C8, CAS No. 111-11-5)

- Methyl decanoate (C10, CAS No. 110-42-9)

- Methyl laurate (C12, CAS No. 111-82-0)

- Methyl myristate (C14, CAS No. 124-10-7)

- Methyl palmitate (C16, CAS No. 112-39-0)

- Methyl stearate (C18, CAS No. 112-61-8)

- Methly oleate (C18, CAS No. 112-62-9)

- Fatty acids, C12-18, Me esters (CAS No. 68937-84-8)

- Fatty acids, C10-16, Me esters (CAS No. 67762-40-7)

 

The following category members, Methyl octanoate (C8, CAS No. 111-11-5), Methyl laurate (C12, CAS No. 111-82-0) and Methyl myristate (C14, CAS No. 124-10-7) are broadly used as food additives and as such were evaluated for their safety as food additives from the Joint FAO/WHO Expert Committee on Food Additives (JECFA) published in the WHO Food Additives Series 40, 1998. For the three substances there is no safety concern at current levels of intake when used as flavouring agents. The intake estimates for the substances were estimated to be in the range of 0.14 ¿g and 9.7 ¿g per person per day.

According to the ECETOC Monograph No. 32 (ISSN-0773-6347-32, Brussels, 2002) on the Use of Human Data in Hazard Classification for Irritation and Sensitisation, "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 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 the food additives mentioned above and at the same time there were no clinical case reports on the sensitisation potential of these substances available, a sensitisation potential appears very unlikely. 

 

 

 


Migrated from Short description of key information:
SCAE Methylester have no skin sensitising potential.

Justification for classification or non-classification

According to DSD and CLP classification criteria for sensitisation, no classification is required for any of the members of the Category SCAE Methylester.