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 only limited data available on the skin sensitisation potential of isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2). 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 of skin sensitisation

CAS

Chemical name

Molecular weight

Sensitisation

111937-03-2 (a)

Isononanoic acid, C16-18 alkyl esters

382.66; 410.72

WoE:
Experimental result and QSAR:
not sensitising
RA: CAS 91031-48-0
RA: CAS 59219-71-5

91031-48-0 (b)

Fatty acids, C16-18, 2-ethylhexyl esters

368.65; 396.70

Experimental result:
not sensitising

59219-71-5

3,5,5-trimethylhexyl 3,5,5 -trimethylhexanoate

284.48

Experimental result:
not sensitising

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

(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 the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Skin sensitisation

CAS 111937-03-2

The summary of a non-guideline study performed by Potokar (1972) with isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2) is available. 5 male guinea pigs/group were given in total 10 intradermal injections of 25% test substance in olive oil or olive oil alone, once every second day during the induction phase until Day 19, and one intradermal challenge treatment with 25% test substance in olive oil on Day 33. There was no positive control group. No sensitisation reactions were observed in the treatment or negative control group.

The skin sensitising potential of isononanoic acid, C16-18 alkyl esters was assessed using the OECD QSAR Toolbox, v2.3 (Nordheim, 2012). The two main monoconstituents (isononanoic acid, C16 alkyl ester and isononanoic acid, C18 alkyl ester) were run in the relevant proprietary QSARs. The monoconstituents were negative for skin sensitisation in the Danish EPA data base and negative for protein/DNA-binding potential (another predictor of skin sensitisation). The BfR rules predicted skin irritation potential and mutagenic potential (OECD, 2012). However, these endpoints were shown to be negative in animal studies (Banduhn, 1988; Dufour, 1991).

In a publication by Le Coz and Bressieux (2003), a case of allergic contact dermatitis was reported in a woman following the application of a urea-based moisturising cream. The patient had a history of allergic contact dermatitis to, among others, colophonium and nickel sulphate. Patch tests were performed with all the ingredients of the cream, with positive reactions to the cream and cetearyl isononanoate (cetearyl alcohol is a mixture of fatty alcohols with C16 and C18 as the main constituents) diluted to 4% in liquid mineral oil. 2% cetyl alcohol in liquid mineral oil gave a negative result. A repeated open application test reconfirmed these results. No skin sensitisation reactions were recorded in 10 voluntary controls tested with 4% cetearyl isononanoate in liquid mineral oil.

CAS 91031-48-0

Fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) was tested for its skin sensitisation potential in a Guinea pig maximization test according to OECD Guideline 406 (Clouzeau, 1991). 20 test and 10 control animals (Dunkin-Hartley guinea pigs) were induced intradermally with the test substance in a 25% dilution in paraffin oil. 7 days later the epidermal induction was performed with the undiluted test substance, as this was found to be slightly irritating in the range finding test. 12 days after the last induction treatment the animals were challenged with a 50% test substance solution in paraffin oil. 24 and 48 hours after the challenge exposure ended, no indications of a skin sensitising potential of the test substance was observed in any animal.

CAS 59219-71-5

The sensitizing potential of 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate (CAS 59219-71-5) was assessed in a Repeated insult patch test (epicutaneous test) performed in 98 human volunteers (29 males, 89 females) (Harrison, 1997). During the induction phase, volunteers were exposed in total nine times at an average of 3 times/week. An occlusive patch with 0.2 mL of the undiluted test substance was applied to the left scapular area for 24 hour. The challenge was performed approximately two weeks after the last induction. The challenge patch was applied to the right scapular area and remained in place for 24 h. The sensitisation reaction at the challenge site was assessed 0, 24, 48 and 72 h after patch removal. During the induction phase, 4/98 exhibited faint, minimal erythema or erythema (score ± or 1) and 2/98 had hyperpigmentation. Following the challenge treatment, 11/98 exhibited faint, minimal erythema or erythema (score ± or 1). These reactions are considered to be irritation reactions. The test material did not induce skin sensitisation in any of the 98 subjects. 

Conclusions for skin sensitisation

A summary of a non-adjuvant study performed with isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2) in guinea pigs was available (Potokar, 1972). No skin sensitisation was observed, and no positive control was included. A Guinea Pig Maximisation Test was performed with the analogue substance Fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0), in which no skin sensitisation was induced (Clouzeau, 1991). The results of a Repeated insult patch test (epicutaneous test) performed in 98 human volunteers with the analogue substance 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate (CAS 59219-71-5) showed that the substance had no skin sensitising effects (Harrison, 1997). In a case report cetearyl isononanoate (cetearyl alcohol is a mixture of fatty alcohols with C16 and C18 as the main constituents) was reported to cause allergic contact dermatitis in a patient with multiple allergies (Le Coz and Bressieux, 2003). The skin reaction could not be replicated in 10 volunteers with no known allergies.

Taking all the available data into consideration, isononanoic acid, C16-18 alkyl esters is considered not to be a skin sensitiser.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.


Migrated from Short description of key information:
Skin sensitisation: not sensitising (based on a weight of evidence approach)

Justification for selection of skin sensitisation endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue, an in vivo study of the target substance and based on the weight of evidence from all available studies.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on substance specific studies and read-across following an analogue approach, the available data on the skin sensitisation potential 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.

There are no data available on respiratory sensitisation.