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 read-across

There are no in vivo data on the skin sensitisation potential of 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate (CAS 59219-71-5). The assessment was therefore based on a weight-of-evidence approach considering QSAR modelling and read across to a study conducted with an analogue (source) substance, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read across approach is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

Skin sensitisation

QSAR predictions

CAS 59219-71-5

The potential for 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate to bind to proteins, known to be indicators of potential skin sensitisers, was predicted in the QSAR OECD Toolbox (Nordheim, 2015). No structural alerts were given for the potential protein binding in the OSIS v1.3 database.

Animal data

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 and under GLP conditions (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. On Day 7 10% SDS was applied to the test site to induce skin irritation. On Day 8 the epidermal induction was performed with the undiluted test substance, as this concentration 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. No positive control was included in the study report. The test substance was not skin sensitising under the conditions of this study.

Human data

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 a total of 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 hours. The sensitisation reaction at the challenge site was assessed 0, 24, 48 and 72 hours after patch removal. During the induction phase, 4/98 exhibited faint, minimal erythema (score ± or 1) and 2/98 had hyperpigmentation. Following the challenge treatment, 11/98 exhibited faint, minimal 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. 

A case report was published by Goossens et al (2008) describing the incidence of allergic contact dermatitis in a patient. A woman with a history of allergic contact dermatitis from a cream reacted to application of a lipstick. Patch testing with the European baseline series (Trolab: Hermal, Reinbek, Germany) and a cosmetics series were performed with negative response. The skin sensitisation score was assessed on Day 2 and 4 after exposure. Patch testing with the individual ingredients of the lipstick was conducted; resulting in reactions to isononyl isononanoate, trioleyl phosphate and oleyl erucate. Additional patch testing with the lipstick ingredients was performed a month later. Van der Bend patch test chambers were attached with Micropore and fixed in place with Mefix adhesive tape. The results were scored according to the International Contact Dermatitis Research Group criteria on Day 2, 4 and 7. The results showed strong vesicular positive reactions to all tested ethanolic dilutions of isononyl isononanoate tested on the forearm, from 20% (which is the actual use concentration in the product) to 1%. On Day 7, the patient developed severe oedema of the whole test area. The 5% preparation in petrolatum gave a negative result. There was a positive reaction to trioleyl phosphate 1% and 5% in petrolatum. The positive result to oleyl erucate (20% in petrolatum) observed in September 2007 could not be reproduced. In June 2008, patch tests using the same methods were performed with analogues, to assess the possiblility of cross-reactions. No positive reactions were observed with cetearyl ethylhexanoate, cetearyl isononanoate , cetyl phosphate, diisopropyl adipate, isodecyl neopentanoate, octyldodecyl neopentanoate, oleyl erucate, and stearyl ethylhexanoate and cetyl hexanoate . Subsequent testing with isononyl isononanoate (5% ethanol) and trioleyl phosphate (1% in pet.) in 20 control subjects gave a negative result.

Overall conclusion for skin sensitisation

In a Repeated insult patch (RIPT) test performed in 98 human volunteers with 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate, no skin sensitising effects were observed. The OECD QSAR Toolbox did not predict protein binding by the target substance. A GPMT study performed with the source substance Fatty acids, C16 -18, 2-ethylhexyl esters (CAS 91031-48-0) was negative. A case study in which a patient suffered allergic contact dermatitis following application of 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoateand trioleyl phosphate is considered to be an incidental occurrence. Despite performing a comprehensive literature review, only one case was retrieved, while more publications would be expected if the target substance had skin sensitising properties. 

Taking into account the available information, 3,5,5 -trimethylhexyl 3,5,5 -trimethylhexanoate is considered to be not skin sensitising.

Migrated from Short description of key information:
Skin sensitisation (GPMT, RIPT): not sensitising

Justification for selection of skin sensitisation endpoint:
Hazard assessment is based on the weight of evidence from all available studies.

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

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate (CAS 59219-71-5), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the data on the target substance and the analogue read across approach, 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.