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 grouping of substances and read-across

There are no data available on the skin sensitising properties of Multi constituent ester of pentaerythritol 2-ethylhexanoate. In order to fulfil the standard information requirements set out in Annex VII-IX 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 health, 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, 1.5, of Regulation (EC) No 1907/2006, whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate andHexanoic acid, 2-ethyl-, 2,2-bis [ [(2-ethyl-1-oxohexyl)oxy] methyl] -1,3-propanediyl esterare selected as source substances for assessment of skin sensitisation.

Skin sensitisation

CAS

-- (a)

7299-99-2 (b)

28510-23-8 (b)

Chemical name

Multi constituent ester of pentaerythritol 2-ethylhexanoate

Hexanoic acid, 2-ethyl-, 2,2-bis [ [(2-ethyl-1-oxohexyl)oxy] methyl] -1,3-propanediyl ester

2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate

MW

388.5 - 640.9g/mol

640.9 g/mol

356.5 g/mol

Skin sensitisation

RA: CAS 7299-99-2; CAS 28510-23-8

Experimental result: not sensitising (HRIPT)

Experimental result: not sensitising (HRIPT)

(a) The substance subject to the REACh Phase-in registration deadline of 31 May 2013 is indicated in bold font.

(b) Reference (read-across) substances are indicated in normal font.

The above mentioned substances are considered to be similar on the basis of the similarities in structure, properties and/or activities. The available endpoint information is used to predict the same endpoint for Multi constituent ester of pentaerythritol 2-ethylhexanoate.

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

The surrogate substance Hexanoic acid, 2-ethyl-, 2,2-bis [ [(2-ethyl-1-oxohexyl)oxy] methyl] -1,3-propanediyl ester was tested in a repeated insult patch test (RIPT) with 113 volunteers between 18 and 65 years old (Tolman and Harrison, 1987). The 29 male and 84 female subjects received a series of nine induction patches on the identical site, which were completed over a period of three weeks. With every patch, 0.2 mL of the pure substance was applied. If a subject was unable to make up a missed patching during the same week, the subject was either patched four days the following week or was repatched at the end of the induction phase. The patches remained in place and kept dry for approximately 24 hours, at which time the patch was to be removed by the subject. After a rest phase of two weeks after the last induction, the challenge patch with 0.2 mL of the substance was applied to a virgin skin site and was removed 24 h later. At this time the skin site was evaluated as well as 48, 72 and 96 h after patching. 1 subject showed faint, minimal erythema 24 h after the challenge, but not at later time points. None of the remaining 97 subjects that completed the study showed any signs of skin effects after the induction or challenge applications. Thus, Hexanoic acid, 2-ethyl-, 2,2-bis [ [(2-ethyl-1-oxohexyl)oxy] methyl] -1,3-propanediyl ester is considered to be not sensitising.

In a similar study the sensitising potential of the structural analogue 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate was evaluated in a repeated insult patch test (RIPT) with 96 human volunteers (Harrison, 1999). This study was confirmed and informed consent free of coercion received in conformity with 21 CFR 50.25, Subtitle A, Protection of Human Subjects. 29 male and 77 female subjects between 18 and 68 years of age received a series of nine induction patchings over a period of approximately three weeks. At every induction time point, 0.2 mL of test substance was applied with a patch, which remained in place and was kept dry for 24 h before removal. The test site was observed and scored 24 h afterwards. A rest period of approximately 14 days followed the last induction and subjects were challenged on a previously untreated site for 24 h. The challenge site and the original test site were observed for skin reactions after 24 h and subjects reported at 48 h, 72 h and 96 h post-patching for additional observations. Only in one of 96 subjects a skin reaction was noted during the induction phase, which was classified as faint, minimal erythema. Since none of the subjects exhibited any skin reaction after one of the challenge applications, no skin sensitisation was observed.

Conclusion

In conclusion, the available data with the analogues 2,2-dimethylpropane-1,3-diyl 2-ethylhexanoate and Hexanoic acid, 2-ethyl-, 2,2-bis [ [(2-ethyl-1-oxohexyl)oxy] methyl] -1,3-propanediyl ester indicate that Multi constituent ester of pentaerythritol 2-ethylhexanoateis considered to be not sensitising to skin.

 


Migrated from Short description of key information:
Repeated insult patch test with human volunteers: not sensitising

Justification for selection of skin sensitisation endpoint:
Data regarding skin sensitisation were assessed from human RIPT.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Justification for selection of respiratory sensitisation endpoint:
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 the substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.