Isooctadecanoic acid, monoester with glycerol

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Analogue justification

There are limited data on the skin sensitisation potential of Glycerol monoisostearate (CAS 66085-00-5) available. The assessment was therefore based on the available data, QSAR modelling and a study conducted with an analogue substance as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. 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 Section 13) and within Chapter 5.1 of the CSR.

Skin sensitisation

CAS No. 66085-00-5

The skin sensitisation potential of Glycerol monoisostearate was studied in guinea pigs in an adapted Guinea Pig Maximisation Test, where no adjuvant was used (CTFA, 1985, cited in CIR, 2004). 10 guinea pigs were injected in the shoulder area with a 2.5% dilution of the test substance (in polyethylene glycol, microcrystalline cellulose and dodecyl benzene sulfonate in physiological saline) on Day 1, and the undiluted test substance was applied to the same skin area for 48 h under an occlusive dressing on Day 5. The animals were challenged with a 50% solution of the test substance in polyethylene glycol and microcrystalline cellulose on Day 12 - 14, using an occlusive patch. The patch was removed after 24 hours, and the skin reaction (erythema) was scored 24 and 48 hours after patch removal. The results of the first challenge yielded one positive reaction at the 24-hour reading time point and two positive reactions at the 48-hour reading time point. Following the second challenge, no positive reactions were noted at any reading time point. The slight sensitisation reactions noted following the first challenge were confirmed by results of the third challenge. As no details on skin reactions were reported for animals of the control group and no positive control was included in the assay, this study does not provide a reliable basis for hazard assessment, and can only be used as supporting evidence in a weight-of-evidence approach.

The composition of the target substance includes the mono- di- and tri-glyceride of isostearate. For each of these forms, the iso-branching may be present as a methyl-, ethyl or propyl-branching, although the branching is always simple. The skin sensitisation potential of the main components of the test substance, also taking into consideration the branching options, was predicted in a QSAR model. In order to make a thorough assessment, the glycerol mono-, di- and triisostearate components and the methyl- ethyl and propyl branching of all 3 components, respectively, were run in the OECD QSAR Toolbox v3.1 (Nordheim, 2014). No structural alerts were given for the potential protein binding in the OASIS v1.2 and OECD databases. The substance did not meet the criteria for assessing protein binding potency. There was no alert for protein binding specifically related to skin sensitisation potential in the OASIS v1.2 database. 

 

In a publication by Inui (2009), a case of skin sensitisation suspected to have been caused by the test substance was described (see section 7.10.4). A female subject presented with a history of persistent itchy and scaly erythema on the lips, lasting several years. Patch testing was performed on the subject; with cosmetic products suspected to have caused the skin reaction and with the individual ingredients of two lipsticks that caused a positive skin reaction. The results for glyceryl isostearate and oleyl alcohol were inconclusive for the Day 2- and positive for the Day 3- reading time point. For diisostearyl maleate and Lithol Rubine BCA the results were negative at the Day 2-hour reading time point and positive at the Day 3-hour reading time point.

Because the exact substance identification, composition and molecular structure of glyceryl isostearate was not defined, it is unclear whether the branching for ‘glyceryl isostearate’ as presented in the publication is the same as, or even similar to, the branching defined for Glycerol monoisostearate (CAS No. 66085-00-5). Therefore it is also unclear whether this case report is relevant to the skin sensitisation assessment for Glycerol monoisostearate.

CAS No. 91845-19-1

The skin sensitising potential of Glycerides, C16-18 and C18-hydroxy mono- and di- was studied in guinea pigs according to the maximisation method (OECD guideline 406) and in compliance with GLP (Kästner, 1985). In three preliminary tests, suitable treatment concentrations for the main study were determined in each 5 animals. For the intradermal route, the test substance at concentrations of 1 and 10 % in paraffin was administered to the clipped skin of 5 animals. Based on the induction of moderate irritant effects on the skin but no necrosis, a test substance concentration of 1% in paraffin oil (w/w) was chosen for intradermal injections in the main study. For the cutaneous route, the test substance at 25 and 50% in vaseline was applied to the clipped skin of 5 animals for 48 h using an occlusive dressing within the preliminary experiment. Since the 50% concentration of the test substance was sufficient to cause skin irritation, this concentration was selected for topical application in the induction phase of the main experiment. For challenge exposure, intradermal injections with Freund’s adjuvant followed by epicutaneous application of 0.2 g of the test substance at concentrations of 25 and 50% in vaseline were performed in the preliminary test. After 24-h exposure under occlusive conditions, slight erythema was observed on the skin of 2/5 animals. Thus, the test substance at 25% in Vaseline was chosen for topical application in the challenge phase of the main test. In the induction phase of the main study, intradermal injections of the test substance at 1% in paraffin and/or FCA were applied into the clipped skin area of 20 females. A control group, consisting of 20 females, was injected with vehicle only and/or FCA. On Day 8, a 48-hour epicutaneous induction treatment with test substance at 50% in vaseline or vehicle only was performed in the treated or control animals on the regions of intradermal injections. On Day 22, the challenge treatment was performed by topical application of the test substance at 25% concentration in vaseline and the vehicle to all animals for 24 h. Skin reactions were evaluated 24 and 48 h after the challenge application. During the study no test substance-related clinical signs and no effects on body weight gain were observed. No cutaneous reactions were provoked by the challenge treatment with the test substance at 25% in none of the animals of the test and control groups. Therefore, the test substance had no sensitising effect in guinea pigs under the experimental conditions chosen.

Conclusion

A weight-of-evidence approach was applied to assess the skin sensitising potential of the test substance Glycerol monoisostearate (target substance). The published summary of an adapted GMPT study on the test substance showed no skin sensitising potential, however, no positive control was listed to provide validation of the method. The glycerol mono-, di- and triisostearate components and the methyl- ethyl and propyl branching of all 3 components, respectively, were run in the OECD QSAR Toolbox v3.1. No structural alerts were given for general protein binding in the OECD QSAR toolbox databases, nor was there an alert for protein binding specifically related to skin sensitisation potential in the OASIS database. This indicates that none of the branching options are likely to cause skin sensitisation. One case report describing a female presenting with allergic contact dermatitis caused by the use of lipstick was retrieved from the public literature. Patch testing of the subject to (among other) glyceryl isostearate resulted in a positive skin reaction. Because the exact substance identification, composition and molecular structure of glyceryl isostearate was not defined, it is unclear whether the branching for ‘glyceryl isostearate’ as presented in the publication is the same as, or even similar to, the branching defined for Glycerol monoisostearate (CAS No. 66085-00-5). Therefore it is also unclear whether this case report is relevant to the skin sensitisation assessment for Glycerol monoisostearate. Furthermore, although the case report indicates that the test substance may have a potential to cause skin sensitisation, it is the only case that was retrieved in a literature search. Generally, for substances used extensively in (among other) cosmetic products over a longer period of time, we would expect more case reports to have be published if a significant potential for skin sensitisation is present. In the source substance Glycerides, C16-18 and C18-hydroxy mono- and di- (CAS No. 91845-19-1), the result of a GMPT study was negative.

Taking into account all the available information, the test substance is considered to be not skin sensitising.

Migrated from Short description of key information:
Based on a weight-of evidence assessment of the available data, the substance is considered to be not skin sensitising.

Justification for selection of skin sensitisation endpoint:
No study was selected, as a Weight of Evidence approach was applied.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available 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.