Decanoic acid, mixed esters with octanoic acid and pentaerythritol

Endpoint summary

Description of key information

Skin sensitisation (OECD 406, Buehler): not skin sensitising

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

JUSTIFICATION OF THE READ-ACROSS ANALOGUE (RA-A) APPROACH

The target substance Tetraesters of 2,2-bis(hydroxymethyl)propane-1,3-diol and decanoic and octanoic acid (CAS No. 68441-68-9) is an ester of pentaerythritol and fatty acids of a chain length of C8 and C10. The analogue approach covers 10 source substances, all of them are polyol esters covering a variety of polyols (pentaerythritol, dipentaerythritol and trimethylolpropane) and fatty acid moieties (linear: C5-18; branched: C5, C8 and C9; unsaturated: C18:1, C18:2 and C18:3).

The available data allows for an accurate hazard and risk assessment of all source substances and the target substance. Therefore, the read-across analogue (RA-A) approach is applied for the assessment of human health hazards of the target substance. Potential human health effects of the target substance are predicted by using adequate and reliable data for source substances within the analogue approach in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, 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 of the read-across is provided in IUCLID section 13.

Target and source substances covered by the RA-A approach:

ID	CAS No.	EC No.	Chemical name	Fatty acid chain length	Type of alcohol	Degree of esterification	Molecular Formula	MW [g/mol]
Target	68441-68-9	270-472-2	Decanoic acid, mixed esters with octanoic acid and pentaerythritol	C8, C10	PE	Tetra	C37H68O8; C45H84O8	640.93 - 753.14
Source 1	11138-60-6	234-392-1	Fatty acids, C8-10 (even numbered), di- and triesters with propylidynetrimethanol	C8, C10	TMP	Tri	C30H56O6; C36H68O6	512.78 - 596.94
Source 2	15834-04-5	239-937-7	2,2-bis[[(1-oxopentyl)oxy]methyl] propane-1,3-diyl divalerate	C5	PE	Tetra	C25H44O8	472.62
Source 3	71010-76-9	275-118-0	Decanoic acid, mixed esters with heptanoic acid, octanoic acid, pentaerythritol and valeric acid	C5, C5iso, C6, C7, C8, C9, C10	PE	Tetra	C25H44O8; C33H60O8; C45H84O8	472.62 - 753.14
Source 4	146289-36-3	--	Pentaerythritol ester of pentanoic acids and isononanoic acid	C5, C5iso, C9branched	PE	Tetra	C25H44O8; C41H76O8	472.62 – 697.04
Source 5	68424-31-7	270-291-9	Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids	C5, C7, C8, C10	PE	Tetra	C25H44O8; C45H84O8	472.62 – 753.14
Source 6	85536-35-2	287-517-7	Fatty acids, C5-9, mixed esters with dipentaerythritol and pentaerythritol	C5-9	PE and DiPE	Tetra and Hexa	C25H44O8; C41H76O8; C40H70O13; C60H110O13	472.62 - 1039.51
Source 7	68604-44-4	271-694-2	Fatty acids, C16-18 and C18-unsatd., tetraesters with pentaerythritol	C16, C17, C18, C18:1, C18:2, C18:3	PE	Tetra	C69H132O8; C77H148O8; C77H104O8	1089.78 - 1193.93
Source 8	189200-42-8	--	Fatty acids, C8-10 mixed esters with dipenaterythritol, isooctanoic acid, pentaerythritol and tripentaerythritol	C8-10, C8iso	PE and DiPE	Tetra	C37H68O8; C45H84O8; C41H76O8; C58H106O13; C70H130O13; C64H118O13	640.93 – 1179.77
Source 9	67762-53-2	267-022-2	Carboxylic acids, C5-9, tetraesters with pentaerythritol	C5-9	PE	Tetra	C25H44O8; C41H76O8	472.62 - 697.04
Source 10	85586-24-9	287-827-2	Fatty acids, C8-10, tetraesters with pentaerythritol	C8-10	PE	Tetra	C37H68O8; C45H84O8	640.93 - 753.14

DISCUSSION

A repeated insult human patch test (RIPT) was conducted to assess the sensitizing potential of Decanoic acid, mixed esters with octanoic acid and pentaerythritol (CAS No. 68441-68-9) in 55 human volunteers from the general population (Key, 1985, RIPT, sec. 7.10.4 of the technical dossier). Induction was carried out by 10 repeated semiocclusive applications of the unchanged test substance. Patches were placed on the back of volunteers for 24 h, followed by a 24 h rest period (48 h 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 h 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.

In addition to the human data of the target substance, information on the skin sensitising potential of the source substance Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7) is used to assess the sensitisation potential of the target substance.

The skin sensitisation potential of Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7) was evaluated in guinea pigs with a Buehler test for (key, RA-A, 68424-31-7, 1991). 20 male albino guinea pigs were treated with the test substance and compared with 10 control animals. Three epidermal inductions were performed with undiluted test substance in weekly intervals for 6 h under occlusive conditions. 14 days after the last induction treatment, all animals were challenged for 6 h epicutaneously with undiluted test substance (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. There was no positive control and no negative control included in the study.

CONCLUSION

No evidence for skin sensitising properties was found in available human data or for the source substance, therefore, the target substance is not predicted to be skin sensitising.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006, information on intrinsic properties of substances may be provided by means other than tests e.g. by transferring information of structurally related substances to a target substance,

provided that conditions set out in Annex XI are met. Annex XI, sec. 1.5, states that “Substances whose physicochemical, 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".

Therefore, Article 13 and Annex XI of Regulation (EC) No. 1907/2006 define the read-across concepts:

(i) read-across based on grouping of substances (category approach) - RA-C approach

(ii) read-across from supporting substance (structural analogue or surrogate) - RA-A approach.

Here the RA-A approach is applied to fill data gaps by transferring data from structural analogues/source substances to the target substance. As a result, unnecessary animal testing is avoided. Therefore, based on the analogue read-across approach, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.