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EC number: 947-748-2 | CAS number: -
Skin sensitisation (OECD 406, GPMT and Buehler): not skin sensitising
Read-across from structural analogue source substances Fatty acids, C5-9 tetraesters with pentaerythritol (CAS No. 67762-53-2), Fatty acids, C8-10 mixed esters with dipenaterythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS No. 189200-42-8), and Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS No. 68424-31-7)
No information on positive control group included in study report.
Justification for grouping of substances and read-across
The analogue approach comprises aliphatic esters of poly-functional alcohols containing four to six reactive hydroxyl groups and one to six fatty acid chains. The read-across analogue approach contains mono constituent, multi-constituent and UVCB substances with fatty acid carbon chain lengths ranging from C5 - C20, which are mainly saturated but also mono unsaturated C16 and C18, polyunsaturated C18 and branched C5, C7 and C9, building mono-, di-, tri-, and tetra esters with the polyol. The available data allow for an accurate hazard and risk assessment of the target substance and the source substances and the read-across concept is applied for the assessment of environmental fate and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substances within the read-across analogue approach by interpolation to the target substances in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006 (REACH). In particular, for each specific endpoint the source substance or substances 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 substance and target substances are the basis of read-across.
A detailed justification for the read-across applied is provided in the technical dossier (see IUCLID Section 7.1 and 13) and within Chapter 5.1 of the CSR.
Skin sensitisation potential
There are several reliable studies available for structural analogue source substances investigating the skin sensitisation potential.
A guinea pig maximisation test (GPMT) was performed with Fatty acids, C5-9, tetraesters with pentaerythritol (CAS No. 67762-53-2) comparable to the OECD Guideline 406 (Exxon, 1999d). A range-finding study was performed for dose selection. 10 albino guinea pigs were treated with the test substance at 5% for intra- and 100% for epidermal induction on days 1 and 7, respectively. 5 animals served as negative controls. A positive control group was not included in the study but information is given on periodical testing of strain sensitivity using hexylcinnamic aldehyde (HCA). 14 days after the epidermal induction, epidermal challenging was performed with 50 and 100% test material dilution in propylene glycol. 24 and 48 hours after challenging skin examination revealed no irritation in the test group and control group. Thus, the test material was found to be not sensitising to the skin of guinea pigs, under the conditions of this test.
A guinea pig maximisation test (GPMT) was performed with Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS No. 189200-42-8) according to a protocol comparable to the OECD Guideline 406 (Exxon, 1995c). A range-finding study was performed for dose selection. 20 female Hartley albino guinea pigs were treated with the test substance at 5% for intra- and 100% for epidermal induction on days 1 and 7, respectively. 10 animals served as negative controls. A positive control group treated with 2-Mercaptobenzothiazole (MBT) (intradermal induction: 3%, epicutaneous induction: 25%, challenge: 0.5%; no rechallenge) was included in the study which showed 100% sensitising reactions. 14 days after the epidermal induction, epidermal challenging was performed with a 50% test material dilution in peanut oil. At the first reading, 24 hours after challenge, skin examination revealed irritation reactions in the test group for 18 of 20 animals and in the control group for 9 of 10 animals. 48 hours after challenge, 7 animals in test and control group each showed skin irritation reactions. Since the 50% challenge concentration resulted in skin irritation, a rechallenge was done using 10% test substance. 5 of 10 control animals (50%) and 4 of 20 (20%) test group animals showed skin irritation 24 hours after rechallenge. All skin reactions were completely reversed 48 hours after rechallenge in both groups. Thus, the test material was found to be not sensitising to the skin of guinea pigs, when used as 5% solution for induction and 10% solution for challenge.
The skin sensitisation potential of Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS No. 68424-31-7) was evaluated in guinea pigs with a Buehler test for (WoE, RA-A, 68424-31-7, 1991d). 20 male albino guinea pigs were treated with the test substance and compared with 10 control animals. Three epidermal inductions were performed with 100 % test substance in weekly intervals for 6 hours under occlusive conditions. 14 days after the last induction treatment, all animals were challenged for 6 hours epicutaneously with 100% (left shorn flank) and 30% (right shorn flank) test substance (diluted in corn oil) under occlusive conditions. Animals were evaluated for skin reactions 24 and 48 h after challenge. No signs for irritation or sensitisation were observed during induction and challenge of the animals.
In addition to the animal-derived data, a repeated insult human patch test (RIPT) was conducted to assess the sensitizing potential of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl (CAS No. 62125-22-8) in 55 human volunteers from the general population (Key, RA-A, 62125-22-8, 1985). Induction was carried out by 10 repeated semiocclusive applications of the unchanged test substance. Patches were placed on the back of volunteers for 24 hours, followed by a 24 hour rest period (48 hours on weekends). The 10 induction patches were applied to the same site. The induction phase was followed by a resting period of 14 days. Challenge patches were applied to the same site on the back and to a naïve site. Skin reactions were assessed 24 and 48 hours after patch removal. None of the human volunteers showed any skin reactions at the end of the study period. Thus, the test material is not considered sensitising to humans.
Conclusion on skin sensitisation
All data indicate no potential for skin sensitisation in adequate GPMT and Buehler tests. Thus, no hazard for skin sensitisation is identified for the target substance Fatty acids lanolin, di-, tri- and tetraesters with pentaerythritol and rape fatty acid.
According to Article 13 of Regulation (EC) No. 1907/2006 (REACH) information on intrinsic properties of substances may be generated by means other than tests, e.g. using information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI states that “substances whose physico-chemical, 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 read-across concept is applied to the target substance Fatty acids lanolin, di-, tri- and tetraesters with pentaerythritol and rape fatty acid, data gaps can be filled by interpolation from representative structural analogue source substances to avoid unnecessary animal testing.
The read-across concept is also used to derive the classification of the target substance taking the properties of the source substances into account. Based on the read-across concept, all available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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