Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Justification for grouping of substances and read-across

There are no data available for the genetic toxicity of fatty acids, C8-10, octyl esters (CAS 91031-98-0). In order to fulfil the standard information requirements set out in Annex IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, a 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 genetic toxicity

CAS #

Genetic toxicity (mutagenicity) in bacteria in-vitro

Genetic toxicity (cytogenicity) in mammalian cells in-vitro

Genetic toxicity (mutagenicity) in mammalian cells in-vitro

Genetic toxicity in vivo

91031-98-0 Target substance

RA: 2306-88-9

RA: 10233-13-3

RA: 26399-02-0

RA: 10233-13-3

RA: 26399-02-0

--

2306-88-9

negative

--

--

--

10233-13-3

--

negative

negative

--

26399-02-0

--

negative

negative

--

 

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, C8-10, octyl esters (CAS 91031-98-0).

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

CAS 2306-88-9

AMES, OECD 471, negative

A bacterial reverse mutation assay was performed with octyl octanoate (CAS 2306-88-9) according to OECD guideline 471 and GLP with the S. typhimurium strains TA98, TA100, TA1535, TA1537 and TA102 (Wollny, 2000). The bacterial tester strains were treated with 33, 100, 333, 1000, 2500 and 5000 µg/plate µg/plate of the test substance in absence and presence of metabolic activation by phenobarbital- and ß-naphthoflavone-induced rat liver S9-mix. Three independent experiments were performed with triplicates each. Sodium azide, 4-nitro-o-phenylene-diamine, methylmethanesulfonate and 2-aminoanthracene were used as positive controls without and with metabolic activation, respectively. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. Neither precipitation nor cytotoxic or genotoxic effects were observed at any concentration neither in the presence nor in the absence of metabolic activation. Based on the study results, octyl octanoate did not induce gene mutations in five tested Salmonella strains.

CAS 10233-13-3

In vitro mammalian chromosome aberration test, OECD 473, negative

The ability of isopropyl laurate (CAS 10233-13-3) to induce chromosome aberrations in cultured peripheral human lymphocytes was tested according to OECD guideline 473 and under GLP (Buskens, 2010). Test substance concentrations of up to 250 µg/mL dissolved in ethanol were tested in the presence and absence of metabolic activation. At concentrations of 100 µg/mL and higher precipitation of test substance occurred. The first experiment was incubated for 3 hours and 24 hours fixation with and without metabolic activation, whereas the second experiment was incubated for 3 hours together with 48 hours fixation (with S9 mix) and 24 and 48 hours incubation without S9 mix followed by 24 and 48 hours fixation, respectively. The number of cells with chromosome aberrations found in the solvent control cultures was within the laboratory historical control data range. Positive control chemicals, Mitomycin C and Cyclophosphamide, both produced a statistically significant increase in the incidence of cells with chromosome aberrations, indicating that the test conditions were adequate and that the metabolic activation system (S9-mix) functioned properly. Isopropyl laurate did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in the absence and presence of S9-mix, in either of the two independently repeated experiments. No effects on the number of polyploid cells and cells with endoreduplicated chromosomes were observed.

CAS 26399-02-0

In vitro mammalian chromosome aberration test, OECD 473, negative

The ability of2-ethylhexyl oleate(CAS 26399-02-0) to induce chromosome aberrations in cultured peripheral human lymphocytes was tested according to OECD guideline 473 and under GLP (Buskens, 2010). Test substance concentrations of up to 33 µg/mL dissolved in ethanol were tested in the presence and absence of metabolic activation. At a concentration of 33 µg/mL precipitation of test substance occurred. The first experiment was incubated for 3 hours and 24 hours fixation with and without metabolic activation, whereas the second experiment was incubated for 3 hours together with 48 hours fixation (with S9 mix) and 24 and 48 hours incubation without S9 mix followed by 24 and 48 hours fixation, respectively. Positive control chemicals, Mitomycin C and Cyclophosphamide, both produced a statistically significant increase in the incidence of cells with chromosome aberrations, indicating that the test conditions were adequate and that the metabolic activation system (S9-mix) functioned properly. 2-Ethylhexyl oleate did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in the absence and presence of S9-mix, in either of the two independently repeated experiments. No effects on the number of polyploid cells and cells with endoreduplicated chromosomes were observed.

CAS 10233-13-3

In vitro mammalian cell gene mutation test, OECD 476, negative

An in vitro mammalian cell gene mutation assay according to OECD Guideline 476 and GLP was performed with isopropyl laurate (CAS 10233-13-3) in mouse lymphoma L5178Y cells (Verspeek-Rip, 2010). The cells were treated for 3 and 24 hours with test substance concentrations up to 10 µg/mL dissolved in ethanol without and with S9-mix, respectively. Precipitation was seen at 10µg/mL. Cyclophosphamide and methylmethanesulfonate were used as positive controls with and without S9 mix, respectively. Positive and vehicle controls were valid. No significant increase in mutation frequency occurred in any of the test conditions, indicating that isopropyl laurate is not mutagenic in the mammalian cells in vitro.

CAS 26399-02-0

In vitro mammalian cell gene mutation test, OECD 476, negative

An in vitro mammalian cell gene mutation assay according to OECD Guideline 476 and GLP was performed with 2-ethylhexyl oleate (CAS 26399-02-0) in mouse lymphoma L5178Y cells (Verspeek-Rip, 2010). The cells were treated for 3 and 24 hours with test substance concentrations up to 100 µg/mL dissolved in ethanol without and with S9-mix, respectively. Precipitation was seen at 100µg/mL. Cyclophosphamide and methylmethanesulfonate were used as positive controls with and without S9 mix, respectively. Positive and vehicle controls were valid. No significant increase in mutation frequency occurred in any of the test conditions, indicating that 2-ethylhexyl oleate is not mutagenic in the mammalian cells in vitro.

 

Conclusion:

One study assessing the potential genetic toxicity using analogue based read-across from structural related substance octyl octanoate (CAS 2306-88-9) in bacteria (Ames test) is available. In vitro chromosomal aberration tests and an in vitro mammalian cell gene mutation assays were also performed with either isopropyl laurate (CAS 10233-13-3) or 2-ethylhexyl oleate (CAS 26399-02-0). The results of all the tests were negative. The available data on genetic toxicity in vitro indicates that the structural related substances do not have genetic toxicity potential.


Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by means of read-across based on an analogue approach. No study was selected since all available in vitro and in vivo 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:
Ames test (OECD 471): negative with and without metabolic activation in S. typhimurium TA98, TA100, TA1535, TA1537 and TA102
Chromosome aberration (OECD 473): negative in Chinese hamster lung fibroblasts (V79) cells with and without metabolic activation
Gene mutation (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

Based on read-across from structurally similar substances, the available data on genetic toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.