Fatty acids, C8-12, isopentyl esters

Endpoint summary

Description of key information

Based on a weight of evidence approach, Fatty acids, C8-12, isopentyl ester has no sensitsing potential.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Sensitisation

Justification for read-across

There are no data regarding sensitisation available for Fatty acids, C8-12, isopentyl ester. In order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.3, read-across from appropriate substances is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5.

According to 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) “to avoid the need to test every substance for every endpoint”.

Fatty acids, C8-12, isopentyl ester is a multi-constituent substance specified by C8, C10 and C12 linear saturated fatty acids esterified with isopentanol resulting in monoesters which meets the definition of an UVCB substance. Thus, the test substance represents fatty acid esters which undergo to a high extent hydrolysis by ubiquitous expressed gastrointestinal enzymes into the free fatty acid components and the respective alcohol (Lehninger, 1970; Mattson and Volpenhein, 1972). Considering the common metabolism, the read-across approach is based on the presence of common functional groups, common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals, common functional groups, structural similarities and similar physico-chemical, toxicological and toxicokinetic behaviour. For further details on the read-across approach, please refer to the analogue justification in section 13 of the technical dossier.

As no data on sensitisation are available for Fatty acids, C8-12, isopentyl ester, read-across to reliable data on the analogue substances Isopropyl Myristate (CAS 110-27-0), Fatty acids, C8-16, 2-Ethylhexyl esters (CAS 135800-37-2) and Isopropyl Laurate (CAS 10233-13-3) was conducted for skin sensitisation. The substances were chosen based on their structural similarities regarding the branched alcohol component (isopropanol or 2-ethylhexanol) and the linear fatty acid component (C12, C14 or C8-16, respectively).

CAS 110-27-0

A Guinea pig maximisation test was performed with Isopropyl Myristate (CAS 110-27-0) according to a protocol similar to the OECD guideline 406 (Potokar, 1984). No range-finding study was performed for dose selection. 15 female Pirbright-Hartley guinea pigs were treated with the test substance at 5% for intra- and epidermal induction on days 1 and 7, respectively. Twenty animals served as negative controls (one control animal died during the study). A positive control group was not included in the study and no information is given on periodical testing of strain sensitivity, either. 14 days after the epidermal induction, epidermal challenge was performed with a 25% test material dilution in 2% Carboxymethylcellulose and 0.5% Cremophor. 48 and 72 hours after the challenge treatment skin examination revealed no irritation in the test group or in the control group. Thus, the test material was found to be not sensitising to the skin of guinea pigs, when used as 5% solution for induction and 25% solution for challenge. Based on the study results no classification is required according to EU classification criteria for skin sensitisation.

CAS 10233-13-3

A Local Lymph Node Assay was performed with Isopropyl Laurate (CAS 10233-13-3) according to OECD guideline 429 and under GLP conditions (Stitzinger, 2010). The skin of the ear of 5 female CBA mice was treated with 25μL of the liquid test substance at concentrations of 25, 50 and 100% diluted with acetone/olive oil (4:1 v/v). Alpha-hexylcinnamicaldehyde was used for the six-month reliability check, indicating the sensitivity of the test method in the laboratory. Measurement of radioactivity showed significantly and dose-dependent increases of the disintegrations per minute/animal values: for the experimental groups treated with test substance concentrations 25, 50 and 100% the values were found to be 620, 1324 and 1929 DPM, respectively (corresponding to SI values of 1.7, 3.5, and 5.1). The mean DPM/animal value for the vehicle control group was 375. However, concomitant erythema of the treated skin sites at test substance concentrations of 50 and 100% were observed. Thus, the results cannot be clearly verified as sensitising effects, as skin irritation could also induce a dose-dependent increase of the stimulation index. Therefore, based on the study result, the test substance cannot clearly be classified as skin sensitizer.

CAS 135800-37-2

A Guinea pig maximisation test was performed with Fatty acids, C8-16, 2-Ethylhexyl esters (CAS 135800-37-2) according to OECD guideline 406 (Steiling, 1991). 19 test and 10 control animals (Dunkin-Hartley guinea pigs) were induced intradermally with 5% test substance (100% pure) diluted in peanut oil on both sides of the spine with and without Freud's complete adjuvant. 7 days later a 40% test substance dilution was used for the epidermal induction for 48 hours. Another 14 days later the animals were challenged by epidermal induction of the sheared flank skin with test substance diluted to 20% with paraffin oil. 24 and 48 hours after termination of challenge exposure skin readings revealed no indications for a skin sensitising potential of the test substance.

In summary, based on the available data on the skin sensitisation properties of the structural analogues, it is concluded, that there is no evidence of sensitising properties of the structural analogues. The described effects in the test with Isopropyl Laurate (CAS 10233-13-3) are regarded rather based on skin irritation than on sensitising potential of the test material.

Conclusion on skin sensitising properties

The available data on the source substances indicate the substances do not have sensitising properties. Thus, Fatty acids, C8-12, isopentyl ester is not expected to be a skin sensitiser.

 

References

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

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 Fatty acids, C8-12, isopentyl ester, data will be generated from information on 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 target substance information and 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.