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 sensitisation potential of Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6).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 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.

 

Overview for skin sensitization

CAS

Skin Sensitization

CAS 68604-38-6 (a)

RA: CAS 68424-31-7

RA: CAS 189200-42-8

RA : CAS 647028-25-9

CAS 68424-31-7 (b)

Not sensitizing

CAS 189200-42-8

Not sensitizing

CAS 647028-25-9

Not sensitizing

 (a) Substances subject to the REACh  Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

 (b) Substances that are either already registered under REACh or not subject to the REACh  Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6)

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

Discussion

Skin Sensitization

CAS 68604-38-6

There are no studies available assessing the skin sensitizing potential of Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6). However, an analogue read-across, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, was applied based on molecular structure similarities and similarities in physicochemical properties to make to investigate Fatty acids C8-10, mixed esters with diPE, isooctanoic acid, PE and triPE (CAS# 189200-42-8).

Four studies were conducted with Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) according to OECD Guideline 406 (Buehler Test) and OECD Guideline 429 (Local Lymph Node Assay). The skin sensitisation potential of Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) was evaluated in guinea pigs with a Buehler test for skin sensitization (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.

Additionally, a Guinea pig maximisation test was performed with Fatty acids C8-10, mixed esters with diPE, isooctanoic acid, PE and triPE (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% sensitizing 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 and 4 of 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.

 

Dipentaerythritol ester of nC5/iC9 acids (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.

 

In summary, due to negative results in all skin sensitization assays, Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6) is not expected to have skin sensitizing properties.

 

Conclusion for skin sensitization

A Buehler Test and two GPMT have been conducted with Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7), Fatty acids C8-10, mixed esters with diPE, isooctanoic acid, PE and triPE (CAS# 189200-42-8), and Dipentaerythritol ester of nC5/iC9 acids (CAS # 647028-25-9). There is no evidence for a skin sensitizing potential in any of these studies.


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. All 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:
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

Based on read-across from the 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.