Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

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

Justification for grouping of substances and read-across

The short chain methyl esters category (SCAE Me) covers fatty acid esters of methanol. The category contains both mono-constituent substances, with fatty acid C-chain lengths ranging from C6 to C18 and UVCB substances, composed of single methyl esters in variable proportions. 

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate, environmental and human health hazards. Thus where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Sections 7.1 and 13) and within Chapter 5.1 of the CSR.

Table: Endpoint Sensitisation

CAS

 

Skin sensitisation

106-70-7 (a)

Experimental result: not sensitising in guinea pig

111-11-5

 Experimental result: inconclusive

110-42-9

RA: 111-82-0

111-82-0

Experimental result: not sensitising in guinea pig

112-39-0

RA: 111-82-0

112-61-8

RA: 111-82-0

112-62-9 (b)

Experimental result: not sensitising in guinea pig

85566-26-3

RA: 111-82-0 and 106-70-7

308065-15-8

RA: 111-82-0

1234694-02-0

RA: 111-82-0, 67762-38-3 and 112-62-9

85586-21-6

RA: 67762-38-3, 112-61-8 and 61788-61-2

67762-38-3

Experimental result: not sensitising in guinea pig

61788-61-2

Experimental result: not sensitising in guinea pig

 

 

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font.

For all category members registered under REACh a full data set for each endpoint is provided. For substances not subject to the current REACh Phase-in registration, lack of data for a given endpoint is indicated by "--".

CAS 111-82-0 

Methyl laurate (CAS 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.

 

CAS 112-62-9 

A Guinea Pig Maximisation Test of Skin Sensitization was performed with methyl oleate (CAS 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.

 

CAS 67762-38-3

Another Guinea Pig Maximisation Test of Skin Sensitization was performed with Fatty acids, C16-18 and C18-unsatd., Me esters (CAS 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.

 

CAS 106-70-7

A Buehler Test on Skin Sensitization was performed with methyl hexanoate (CAS 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.

 

CAS 111-11-5

Data access to an existing LLNA study was not available prior to submission. On receipt of the LoA, the dossier will be updated.

Methyl octanoate showed sensitising effects in the LLNA study. However, the effects in the study are not consistent with the negative skin sensitisation results from all other category members, which were studied in the guinea pig. Against this background, it is thought likely that the LLNA revealed a false positive result, either caused by an irritating effect in the test animals, or because of non-identified impurities in the test material. In order to test this theory, an in-vitro sensitisation test battery (consisting of 3 individual tests) is currently ongoing. If justified, another in-vivo test will be conducted. The dossier will be updated as soon as possible and the Chemical Safety Assessment according to Annex I of Regulation (EC) No 1907/2006 will be re-evaluated based on the outcome of the new studies.

 

CAS 61788-61-2

A Guinea Pig Maximisation Test of Skin Sensitization was performed with Fatty acids, tallow, methyl esters (CAS 61788-61-2) according to OECD Guideline 406 under GLP conditions (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 dinitrochloro-benzene and benzocaine as positive control substances. A 5% dilution of the test substance in peanut oil was used for intradermal induction on day 1 and 100% used for epidermal induction of the trunk region on day 8. 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.

Additionally, the following category members, Methyl octanoate (C8, CAS 111-11-5), Methyl laurate (C12, CAS 111-82-0) and Methyl myristate (C14, CAS 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 μg and 9.7 μg 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. 

Conclusions:

Taken together, all available and reliable experimental animal data indicate that members of the Fatty acid methyl esters category have no skin sensitisation potential. The available data for Methyl octanoate are currently insufficient for the assessment of the skin sensitising properties, and thus the hazard assessment for this endpoint is considered as inconclusive for the time being. An update of this dossier will be submitted as soon as possible.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.


Migrated from Short description of key information:
All available studies showed no skin sensitisation potential of the category members.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the group concept is applied to the members of the SCAE Me category, data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the group concept, the available and reliable data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

The available data for Methyl octanoate are currently insufficient for the assessment of the skin sensitising properties, and thus the hazard assessment for this endpoint is considered as inconclusive for the time being.