Isononanoic acid, mixed esters with dipentaerythritol, heptanoic acid and pentaerythritol

Endpoint summary

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 only limited data available on the skin sensitisation potential of the substance 3,5,5-trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB). 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 out 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 toxicological properties may be predicted from data for the reference substance(s) on the basis of structural similarity, the substances 3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 84418-63-3), 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS 131459-39-7) and Dipentaerythritol ester of fatty acids C5 and C9iso (CAS 647028-25-9) are selected as reference substances for assessment of toxicological endpoints, for which information gaps are identified.  

Discussion

Skin Sensitisation

Beside a human repeated insult patch test no further animal studies investigating the skin sensitisation potential of 3,5,5 -trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB) are available, to strenghten the available results, and in accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across to the structurally related analogue substances 3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 84418-63-3), 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS 131459-39-7) and Dipentaerythritol ester of fatty acids C5and C9iso (CAS 647028-25-9) was conducted.

 

Animal studies

CAS 84418-63-3

3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 84418-63-3) was tested for its skin sensitisation potential with a method equivalent to OECD Guideline 406 (McCall, 1991). 20 male Dunkin-Hartley guinea pigs were tested in a Buehler test and compared with 10 control animals. 100% dilution of the test substance in corn oil was used for epicutaneous induction. Challenge treatment performed by dermal application of the test substance at dilution of 30 % and 100% in corn oil did not elicit a skin sensitisation response. 

CAS 131459-39-7

A Guinea Pig Maximisation Test was performed with 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS 131459-39-7) according to OECD Guideline 406 (Allen, 1999). 10 male Dunkin-Hartley guinea pigs were treated with the test substance and compared with 4 negative control animals. The sensitivity of the animal strain was periodically tested using PEG 400 70:30 in acetone as positive control substance. A 25% dilution of the test substance in arachis oil was used for intradermal induction and 100% used for epidermal induction. 14 days after the last induction treatment, all animals were challenged epicutaneously with the 75% and 100% 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 647028-25-9

Dipentaerythritol ester of fatty acids C5 and C9iso (CAS 647028-25-9) was tested in a Guinea pig maximisation test according to OECD guideline 406 under GLP conditions (Allen, 1999).

In a preliminary range finding test, the suitable concentrations for the main study for the intradermal injection and the patch testing were identified. In the main study, Dunkin-Hartley guinea pigs (10 in test group, 5 controls) were induced with a single intradermal injection of the test substance at 25% in arachis oil and an epicutaneous occlusive application of the test substance at 100% on the shoulder region 7 days later. The negative control group was treated with arachis oil. Epicutaneous challenge exposure was done 20 days after the first induction for 24 h under occlusive conditions. 100% and 75% of the test substance were applied on the right and left flank, respectively. Evaluation of skin reactions was carried out 24 and 48 h after patch removal.

All test and control animals revealed no skin reactions after 24 and 48 h.

The positive control substance 2-Mercaptobenzothiazole was used for intradermal inductions at 10% in arachis oil and for topical inductions at 50% in acetone/PEG400. Challenge induction with 50 and 25% Mercaptobenzothiazole in acetone/PEG400 showed 10/10 incidences of sensitisation in the most recent positive control test.

Under the experimental conditions described, it was concluded, that no evidence of skin sensitisation were seen after treatment with the test substance.

Human data

Additional human data are available for the registered substance 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB, CAS 84418-63-3), as a repeated insult patch test (RIPT) was done according to the method of Marzuli and Maibach. The test-substance was applied to the upper back of 56 volunteers under occlusive conditions for 48 h, 3 times a week for 3 weeks and graded for skin reactions. After a two weeks resting period, the challenge patches were applied to previously treated and unexposed sites for 48 h and analysed for dermal reactions after 48, 72 and 96 h. Only one volunteer showed clear skin reactions. 2 volunteers showed equivocal skin reactions. All other 53 volunteers were without any reaction. Therefore, 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol (CAS 84418-63-3, UVCB), was found not to be sensitizing or irritating to the human skin.

 

Conclusion for skin sensitization

In total two GPMT and one Buehler assay are available with the structural related substances 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS 131459-39-7), Dipentaerythritol ester of fatty acids C5 and C9iso (CAS 647028-25-9) and 3,5,5-trimethylhexanoic acid hexaester with dipentaerythritol (monoconstituent, CAS 84418-63-3), respectively and did not reveal skin sensitising properties.

In addition human data on the registered substance itself show that 3,5,5 trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB, CAS 84418-63-3), is not sensitising or irritating to the human skin. As there is no evidence for a skin sensitizing potential found in any of these assays 3,5,5 -trimethylhexanoic acid, mixed esters with dipentaerythritol (UVCB, CAS 84418 -63 -3) is not considered to have skin sensitizing potential.

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

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

Justification for classification or non-classification

Based on read-across from structurally similar substances, 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.