Registration Dossier

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Administrative data

Description of key information

Skin sensitisation: not sensitising (OECD 406, analogue approach)

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the polyol esters family will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the polyol esters family will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

Justification for grouping of substances and read-across

There are no data available on the skin sensitisation potential of the substance Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1). 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 listed below are selected as reference substances for assessment of toxicological endpoints, for which information gaps are identified.

Overview of skin sensitisation

CAS

Skin Sensitisation

70983-72-1 (a)

RA: CAS 68424-31-7

RA: CAS 131459-39-7

68424-31-7 (b)

Not sensitising

131459-39-7

Not sensitising

 (a) Substances subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold. 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.

The above mentioned substances are considered to be similar on the basis of the structural and similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1).

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

 

Since no studies investigating the sensitisation of Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1) are available, in accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substances Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7), and 3,5,5-trimethylhexanoic acid mixed tetraesters with PE and valeric acid (CAS# 131459-39-7) was conducted.

 

CAS 68424-31-7

 

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 (Croda, 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.

 

This result is supported by the results of a Local Lymph Node Assay which was reported only as a short summary (Croda, 1992). No details on the study protocol or the data interpretation was given. Nevertheless, the data presented (concentrations of the test sample were 1%, 3%, and 10%, CPM/lymph node and the test/control ratio, accordance to GLP) indicate that the test substance was not a sensitizer under the conditions tested.

 

Furthermore, another Local Lymph Node Assay was conducted (Croda, 1991b). The test substance was applied in concentrations of 3%, 10% and 30% on three consecutive days to the dorsum of both ears of 4 female CBA/Ca mice each. Five days later the animals received approx. 20 µCi of 3H-methyl thymidine and were sacrificed 5 h later for measurement of radioactivity. No significant increase in isotope incorporation was detected after repeated application. The stimulation index, calculated by comparison of the Cpm of the control and the treated animals, was 0.45 for the 3% application, 2.05 for 10% and 1.21 for the 30% application. According to the provider, the test substance contained up to 2% of an additional package which was not further defined. This might contribute to the result of this test. Therefore the result cannot be clearly assigned to the test substance and this study is not considered for classification.

In a fourth study, a Local Lymph Node Assay, was conducted analogously to the one reported previously but with significant methodical deficiencies (Croda, 1991c). Only low (3%) and medium (10%) concentrations of the test substance (again containing the additives which were not further specified) were applied instead of the three as demanded by the regulatory authorities. Therefore the results obtained do not allow the derivation of a dose dependency and are insufficient for assessment.

  

Based on the study results no classification is required according to EU classification criteria for skin sensitisation.

 

CAS 131459-39-7

A Guinea Pig Maximisation Test was performed with 3,5,5-trimethylhexanoic acid mixed tetraesters with PE and valeric acid (CAS# 131459-39-7) according to OECD Guideline 406 (Croda, 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.

Taken together, all available experimental data did show no skin sensitisation potential.

 

Conclusion for skin sensitization

1 GPMT and 1 Buehler assays have been conducted withthe structural related read-across analogue substances Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) and 3,5,5-trimethylhexanoic acid mixed tetraesters with PE and valeric acid (CAS# 131459-39-7).There is no evidence for a skin sensitizing potential in these assays. Additionally, 3 LLNAs are available all conducted with Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7), of which only one is suitable for assessment and shows a negative result as well. Therefore, based on a structural related read-across approach,in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, Fatty acids C5-10 esters with dipentaerythritol (CAS# 70983-72-1)is not considered to have skin sensitizing potential.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

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.