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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:

Justification for grouping of substances and read-across

There are no data available for the skin sensitisation potential of 2,2-bis[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate (CAS 25811-35-2). In order to fulfil the standard information requirements set out in Annex VII, 8.3 in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted. In accordance with Article 13 (1) of Regulation (EC) No 1907/2006 “information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set put in Annex XI are met”. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substance listed below are selected as reference substances for hazard assessment.

Overview of skin sensitisation

CAS

Skin sensitisation

25811-35-2

Target substance

RA: CAS 67762-53-2

RA: CAS 68424-31-7

RA: CAS 189200-42-8

67762-53-2

not sensitising

68424-31-7

not sensitising

189200-42-8

not sensitising

CAS 67762-53-2

A Guinea pig maximisation test was performed with Fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) comparable to the OECD Guideline 406 (Zolyniene, 1999). 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% 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.

CAS 68424-31-7

Four studies were conducted with Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids

(CAS 68424-31-7) according to OECD Guideline 406 (Buehler Test) and OECD Guideline 429 (Local Lymph Node Assay). In the first test, the skin sensitisation potential of the test substance was evaluated in guinea pigs with a Buehler test for (Lees, 1991a). 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.

This result is supported by the findings of a Local Lymph Node Assay (Bugg, 1992). Only a short summary with no details on the study protocol or data interpretation was given. Nevertheless, test substance concentrations of 1%, 3%, and 10% indicated that the test substance was not a sensitizer under the conditions chosen.

Furthermore, another Local Lymph Node Assay was conducted (Robinson, 1991b). The test substance was applied in concentrations of 3%, 10% and 30% on three consecutive days to the dorsum of both ears of 4 female CBA/Ca mice each. Five days later the animals received approx. 20 µCi of 3H-methly thymidine and were sacrificed 5 h later for measurement of radioactivity. No significant increase in isotope incorporation was detected after repeated application. The stimulation index, calculated by comparison of the CPM of the control and the treated animals, was 0.45 for the 3% application, 2.05 for 10% and 1.21 for the 30% application. According to the provider, the test substance contained up to 2% of an additional package which was not further defined. This might contribute to the result of this test. Therefore the result cannot be clearly assigned to the test substance and this study is not considered for classification.

In a fourth study, a Local Lymph Node Assay, was conducted analogously to the first one reported for the test substance, but with significant methodical deficiencies (Robinson, 1991c). The test substance was investigated at low concentrations of 3 and 10%. In addition, the test substance comprised additives which were not further specified. Therefore the results obtained do not allow the derivation of a dose dependency and are insufficient for assessment.

CAS 189200-42-8

A guinea pig maximisation test was performed with Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 189200-42-8) according to a protocol comparable to the OECD Guideline 406 (Trimmer, 1995). 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. Based on the study results no classification is required according to EU classification criteria for skin sensitisation.


Migrated from Short description of key information:
Skin sensitisation: not sensitising (OECD 406, analogue approach)

Justification for selection of skin sensitisation endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. The available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Migrated from Short description of key information:
Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

The available data on skin sensitisation of structurally related substances 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.

 

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