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 read-across approach

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 reference substance(s) by interpolation to other substances on the basis of structural similarity, the following substances are selected as reference substances for assessment of toxicological endpoints, for which information gaps are identified.

Therefore, the analogue approach endpoint information for

-         acute toxicity via inhalation forFatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) and Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol (CAS 85536-35-2)

-         the subchronic oral repeated dose toxicity forpentanoic acid, mixed esters with pentaerythritol, isopentanoic and isononanoic acid (CAS No. 146289-36-3);

-         the genetic toxicity information for pentaerythritol tetravalerate (CAS 15834-04-5) and Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7)

-         and information for developmental toxicity for Fatty acids C8-10, mixed esteres with diPE, isooctanoic acid, PE and triPe (CAS 189200-42-8) and Trimethylolpropane Caprylate Caprate (CAS 11138-60-6)

are used to predict the same endpoints for dipentaerythritol ester of nC5/iC9 acids (CAS No. 647028-25-9). The analogue substances are considered to be similar on the basis of structural similarity and similar properties and/or activities.

The structural similarities are based on:

(1) common functional groups: The source (reference) and target substances are all characterised by ester bond(s) between a polyol and one or more carboxylic fatty acid chains. The polyol moiety of the source and target substances comprises structurally related molecules: pentaerythritol, di-pentaerythritol, tri-pentaerythritol and trimethylolpropane, all of which share a neopentane backbone as underlying common molecular structure. The fatty acid moieties comprise saturated linear and/or branched chains of 5 to 10 C-atoms length.

(2) common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals. The source and target substances are all UVCB substances, except pentaerythritol tetravalerate (CAS 15834-04-5) which is a monoconstituent, produced by esterification of the corresponding polyol and fatty acid mixtures. Ester bond formation is in principle a reversible reaction (hydrolysis). A slow stepwise hydrolysis of the ester bonds by gastrointestinal enzymes is identified as the biological process, by which the breakdown of the source and target substances results in structurally similar chemicals: the respective polyol and fatty acid moieties as stated above.

(3) a constant pattern in the changing of the potency of the properties between source and target substances: For the source and target substances, the constant pattern is characterised by similarities in the potency of properties. The available data on the target and the source substances show similarities in physico-chemical properties, in particular the high molecular weight of the substances. The molecular weight of Dipentaerythritol ester of nC5/iC9 acids ranges from 983 to 1096 g/mol and molecular weights of the target substances ranges from 472.62 to 1039.5 g/mol. In addition, the octanol/water partition coefficient of Dipentaerythritol ester of nC5/iC9 acids is > 6.2 (Lumsden, 2000) and available data on the calculated partition coefficients of the target substances are in the range of 6.74 to 13.59 (as published in respective dossiers on ECHA homepage). Furthermore, the target substance has a low water solubility (see toxicokinetics) and calculated water solubility of the source substances is considered to be low as well (Lumsden, 2000).

The available data on toxicological properties indicate that the source and target substances have a similar toxicokinetic behaviour; especially they are assumed to be slowly hydrolyses (see toxicokinetics). In addition, a low acute oral toxicity was seen for the source substance as well as for Trimethylolpropane Caprylate Caprate and Fatty acids, C5-10, esters with pentaerythritol (as published in respective dossiers on ECHA homepage). A low acute inhalation toxicity for Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol and Fatty acids, C5-10, esters with pentaerythritol was observed as well (Parr-Dobranski, 1994a,b). Dipentaerythritol ester of nC5/iC9 acids is not skin or eye irritating and have not shown sensitising properties (Allen, 1999a,b,c) and the same is true for the source substances Fatty acids, C5-10, esters with pentaerythritol and Trimethylolpropane Caprylate Caprate (as published in respective dossiers on ECHA homepage). A low toxicity after repeated oral exposure (NOAEL > 1000 mg/kg bw/day) were observed for the source substance and for Fatty acids, C5-10, esters with pentaerythritol (Jones, 2000; Brammer, 1993) and for pentanoic acid, mixed esters with pentaerythritol, isopentanoic and isononanoic acid (NOAEL = 300 mg/kg bw/day; Müller, 1998). In addition, the available data on genotoxicity show that Dipentaerythritol ester of nC5/iC9 acids and the target substance Trimethylolpropane Caprylate Caprate are not genotoxic in the bacterial reverse mutation assay or clastogenic (Thompson, 1992; Wright, 2000; as published in respective dossier on ECHA homepage) and the source substance pentaerythritol tetravalerate did not show genotoxicity in a mammalian cell gene mutation assay (Verspeek-Rip, 2010). The target substance, Fatty acids, C5-10, esters with pentaerythritol did not show clastogenic properties in vivo as well (Griffiths, 1992) and no effect on intrauterine development was seen for Trimethylolpropane Caprylate Caprate and Fatty acids C8-10, mixed esteres with diPE, isooctanoic acid, PE and triPe.

In summary, all available data on the source and target substances show that the constant pattern is characterised by a lack of potency of properties.

In order to avoid the need to test Dipentaerythritol ester of nC5/iC9 acids for every endpoint, the analogue concept (read-across approach) is applied for the assessment of human health hazards. Thus where applicable, human health effects are predicted from adequate and reliable data for the reference substances by interpolation to Dipentaerythritol ester of nC5/iC9 acids in accordance with Annex XI, Item 1.5 of Regulation (EC) No 1907/2006.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13) as well as in the Chemical Safety Report.

The skin sensitising potential of Dipentaerythritol ester of nC5/iC9 acids 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 determined. 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 showed no skin reactions after 24 and 48 h.

The 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 properties were seen after treatment with Dipentaerythritol ester of nC5/iC9 acids.


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

Justification for selection of skin sensitisation endpoint:
Only one study available.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

This information is not available.

Justification for classification or non-classification

The available data on the skin sensitising potential of Dipentaerythritol ester of nC5/iC9 acids (CAS No. 647028-25-9) do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.