Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: not irritating (OECD 404, GLP, analogue approach)
Eye irritation: not irritating (OECD 405, GLP, analogue approace)

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

There are no data available on the skin and eye irritation potential of Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-5-6). In order to fulfil the standard information requirements set out in Annex VIII, 8.1 and 8.2, 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 and eye irritation

CAS

Skin Irritation/Corrosion

Eye Irritation/Corrosion

CAS 68604-38-6 (a)

Target substance

RA: CAS 85116-93-4

RA: CAS 647028 -25 -9

Not irritating in vitro

RA: CAS 85116-93-4 

RA: CAS 647028 -25 -9

CAS 85116-93-4 (b)

Not irritating

Not irritating

CAS 647028-25-9

Not irritating

Not irritating

 (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# 68604-38-5-6).

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

 

Discussion

Skin Irritation

CAS 68604-38-6

There is only one skin irritation study available which was conducted with human volunteers assessing the skin irritation potential of Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6). The substance was applied undiluted to the back of 12 volunteers (Guibaud, 2004). Only limited reporting is available. No irritation was seen at the end of the exposure period.

 

Additionally, an analogue read-across approach, 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 further evaluate skin irritation.

 

A primary dermal irritation study was performed with Fatty acids, C16-18, esters with pentaerythritol (CAS# 85116-93-4) according to OECD Guideline 404 and GLP (Steiling, 1991). The shaved backs of three male Kleinrussen, Chbb:HM rabbits were exposed to 0.5 g unchanged test material for 4 hours under semiocclusive conditions. The rabbits were observed for 3 days following exposure. Skin reactions were assessed according to Draize score1, 24, 48 and 72 hours after removal of the test substance. No erythema and no oedema occurred in any of the tested animals at any reading time point. The test material is not considered irritating to the skin in this study.

 

The skin irritation properties of Dipentaerythritol ester of nC5/iC9 acids were tested in a study according to OECD guideline 404 in compliance with GLP (Allen, 1999).

In the study, 3 New Zealand White rabbits were exposed to 0.5 mL of the undiluted test substance, applied onto the shaved skin for 4 h under semiocclusive conditions. Thereafter, the remaining test substance was removed, the treated skin was observed and evaluated at 1, 24, 48 and 72 h and 7 days post-application.

The observed skin effects consisted of slight erythema in 2/3 animals from 24 h up to 72 h being fully reversible within 7 days. In the remaining animal, slight erythema was observed at the 24 and 48 h reading time points only. In 2/3 animals mean erythema scores (24, 48 and 72 h) were 1, in one animal the mean erythema score was 0.67. No edema formation (mean over 24, 48 and 72 h) or further local or systemic effects were apparent in any animal during the study period.

Under the experimental conditions described, it was concluded, that no evidence of skin irritation properties were seen after treatment with the test substance.

 

Eye Irritation

CAS 68604-38-6

There are 2 in vitro eye irritation studies available Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6). For both studies only limited reporting is available.

In a HETCAM assay with limited reporting Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6) was tested for its acute eye irritation potential in vitro (Boue-Grabot, 2004). The chorioallantoic membranes of chicken eggs were exposed to the test substance. The irritation score was reported to be 0. Thus, the test material is not considered corrosive to the eyes in this test but further evaluation regarding irritation potential is necessary.

 

In another in vitro study with limited reporting Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6) was tested for its cytotoxicity in fibroblasts (Boue-Grabot, 2004). The Ocular Irritation Index in fibroblasts (IOeq) based on cytotoxicity was found to be 4.3. Since no data are given on interpreting this index it is concluded that a slight irritation potential was observed in this assay applying expert judgement. However, the result needs to be evaluated in vivo.

 

Since, there are no primary in vivo eye irritation studies available for Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol (CAS# 68604-38-6) the eye irritation potential was assessed using an analogue read-across, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, based on molecular structure similarities and similarities for physic chemical properties from Fatty acids, C16-18, esters with pentaerythritol (CAS# 85116-93-4).

Fatty acids, C16-18, esters with pentaerythritol (CAS# 85116-93-4) was tested for its acute eye irritation potential in a study performed according to OECD Guideline 405 under GLP conditions (Steiling, 1991). The undiluted test material (0.1 mL) was applied into the conjunctival sac (the untreated eye served as control) of three male Kleinrussen, Chbb:HM rabbits. The animals were observed for 72 hours and reactions were assessed 1, 24, 48, and 72 h after instillation according to the Draize scoring system. No effects were observed except a very mild and reversible exudation reaction in one out of three animals 24 h after application. Thus, the test material is not considered irritating to the eyes in this study. 

In another study, the eye irritation properties of Dipentaerythritol ester of nC5/iC9 acids (CAS# 647028-25-9) were tested in a study according to OECD guideline 405 under GLP conditions (Allen, 1999).

In a group of 3 New Zealand White rabbits (1 male and 2 females), 0.1 mL of the undiluted test substance was applied into the conjunctival sac of one eye (the untreated eye served as control) in a single application without washing. The eyes were observed and reactions were evaluated 1, 24, 48 and 72 h after application according to the Draize scoring system.

No effects on corneal opacity and iris were noted at any time point in any animal. However, mild and moderate conjunctival redness were noted at the 1 h observation in 1/3 and 2/3 animals, respectively. Moderate conjunctival redness persisted in 2 animals up to the 24 h reading time point (mean score over 24, 48 and 72 h in each of the two animals: 0.33). Minimal chemosis was observed in all treated animals at the 1 h observation. Treated eyes appeared normal 24 to 48 h after treatment.

No further local or systemic effects were observed in any animal during the study period.

Under the experimental conditions described, it was concluded, that no evidence of eye irritation properties were seen after treatment with the test substance.

 

Conclusion for skin and eye irritation

There is one skin irritation study available with a structure related substance Fatty acids, C16-18, esters with pentaerythritol (CAS# 85116-93-4) which show is no indication for skin irritation.

Eye irritation potential has also been investigated based on an analogue read-across approach with Fatty acids, C16-18, esters with pentaerythritol (CAS# 85116-93-4) and Dipentaerythritol ester of nC5/iC9 acids (CAS# 647028-25-9) in an in vivo assay. There was no indication of eye irritating potential. Therefore Fatty acids, C16-18 and C18-unsatd., hexaesters with dipentaerythritol is not considered to be eye irritating.


Justification for selection of skin irritation / corrosion 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).

Justification for selection of eye irritation 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).

Justification for classification or non-classification

Based on read-across from the structurally similar substances, the available data for skin and eye irritation 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.