Fatty acids, C8-C18 (even numbered), decyl esters

Endpoint summary

Additional information

Justification for read-across

Data on the genetic toxicity of Fatty acids, coco, decyl esters (CAS 93455-79-9) are not available. The assessment was therefore based on studies conducted with analogue substances as part of a read across approach, 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 analogue read-across approach is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

Genetic toxicity (mutagenicity) in bacteria in vitro

CAS 95912-86-0

The in-vitro genetic toxicity of Fatty acids, C8-10, C12-18 alkyl esters (CAS 95912-86-0) was assessed in a bacterial reverse mutation assay (Ames test) (Banduhn, 1989). The study was performed equivalent to OECD Guideline 471, but without the required TA 102 or E. coli strain. The plate incorporation method was applied using S. typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 1538 at concentrations up to 5000 µg/plate. The test substance did not induce an increase in reversions in any of the S. typhimurium strains with or without metabolic activation. Cytotoxicity was observed at 5000 µg/plate, with and without metabolic activation. The controls were valid.

CAS 2306-88-9

The mutagenic potential of octyl octanoate (CAS 2306-88-9) was tested in a Salmonella typhimurium reverse mutation assay according to OECD Guideline 471 (Wollny, 2000). The following strains were used: TA 1535, TA 1537, TA 100, TA 98 and TA 102. Tester strains were incubated with the test substance up to the limit concentration of 5000 µg/plate, with and without the addition of a metabolic activation system. Experiment I was carried out as a plate incorporation assay, while experiments II and III were performed as pre-incubation assays. No cytotoxicity of the test substance was observed. Due to slightly induced numbers of revertant colonies for strain TA 1535 without metabolic activation in the second experiment, a third experiment was carried out for strain TA 1535 under the same conditions and at concentrations of 333, 1000, 2500 and 5000 µg/plate. No relevant increase in the number of revertant colonies occurred in the repeat experiment and the effect observed in the second experiment was considered to be biologically irrelevant. The controls were shown to be valid.

 

Genetic toxicity (cytogenicity) in mammalian cells in vitro

CAS 26399-02-0

The cytogenetic potential of 2-ethylhexyl oleate (CAS 26399-02-0) was assessed in an in vitro mammalian chromosome aberration test in primary human lymphocytes, performed according to OECD Guideline 473 (Buskens, 2010). Duplicate cultures of human lymphocytes were evaluated for chromosome aberrations in the presence and absence of metabolic activation. In the first experiment, cells were incubated with test substance concentrations of 3, 10 and 33 µg/mL in ethanol for 3 hours with a 24 hours fixation time in the absence and presence of a metabolic activation system. In the second experiment cells were incubated with 3, 10 and 33 µg/mL for 24 hours followed by 24 hours expression time and for 48 hours following 48 hours expression time, all without metabolic activation. In the presence of metabolic activation 2-ethylhexyl oleate was also tested with 3, 10 and 33 µg/mL for 3 hours followed by 48 hours expression time. 33 µg/mL was chosen to be the maximum concentration due to the limited solubility of the test substance. The test substance caused modest cytotoxicity. The vehicle (solvent) and positive controls were shown to be valid. The test material did not induce a statistically significant increase in the frequency of cells with chromosome aberrations, with or without metabolic activation.

Genetic toxicity (mutagenicity) in mammalian cells in vitro

CAS 26399-02-0

An in vitro mammalian cell gene mutation assay was performed with 2-ethylhexyl oleate (CAS 26399-02-0) according to OECD Guideline 476 (Verspeek-Rip, 2010). Two independent experiments (with 3 or 24 hours of exposure) were performed in mouse lymphoma L5178Y cells in the absence and presence of metabolic activation (S9-mix) with test substance concentrations up to 100 μg/mL dissolved in ethanol. Precipitation was seen at concentrations of 100 µg/mL and higher. The positive and negative controls were valid and within the range of historical control data. No significant increase in mutation frequency was observed.

 

Overall conclusion for genetic toxicity

There are no available studies on the genetic toxicity of the target substance Fatty acids, coco, decyl esters.Therefore analogue read-across from source substances was applied from in vitro studies on cytogenicity and gene mutation in bacteria and mammalian cells,using 3 source substances. The results of the available in vitro studies were negative.

Based on the available data and following the analogue approach, Fatty acids, coco, decyl esters is considered to be not mutagenic and clastogenic in vitro.

Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by means of read-across from structural analogues. All available in vitro genetic toxicity studies were negative. 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).

Short description of key information:
Genetic toxicity in vitro:
Ames test (OECD 471): negative with and without metabolic activation in S. typhimurium TA 1535, TA 1537, TA 100, TA 98, TA 1538 and TA 102.
Chromosome aberration (OECD 473): negative in primary human lymphocytes cells with and without metabolic activation.
Gene mutation in mammalian cells (OECD 476): negative in L5178Y mouse lymphoma cells with and without metabolic activation.

Endpoint Conclusion: No adverse effect observed (negative)

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, coco, decyl esters (CAS 93455-79-9), 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 analogue read-across approach, the available data on genetic toxicity 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.