Hexadecyl 2-ethylhexanoate

Endpoint summary

Additional information

Justification for grouping of substances and read-across

There are sufficient data available for the genetic toxicity of Hexadecyl 2-ethylhexanoate (CAS No. 59130-69-7). In order to fulfil the standard information requirements set out in Annex IX 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, 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.

Genetic toxicity

CAS	59130-69-7	26399-02-0
Chemical name	Hexadecyl 2-ethylhexanoate	2-ethylhexyl oleate
MW	368.7 g/mol	394.7 g/mol
Genetic Toxicity in vitro: gene mutation in bacteria	Experimental result: negative	-
Genetic Toxicity in vitro: cytogenicity in mammalian cells	RA: CAS 26399-02-0	Experimental result: negative
Genetic Toxicity in vitro: gene mutation in mammalian cells	RA: CAS 26399-02-0	Experimental result: negative

 

The above mentioned substances are considered to be similar on the basis of the structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Hexadecyl 2-ethylhexanoate (CAS No. 59130-69-7).

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

Discussion

Genetic toxicity in vitro

In vitro gene mutation in mammalian cells

Gene mutation in bacteria byHexadecyl 2-ethylhexanoatewas analyzed in a GLP study performed according to OECD guideline 471 (Haddouk, 2007). Bacteria strains S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 were treated with the test substance (diluted in ethanol) at concentrations of 312.5, 625, 1250, 2500, 5000 µg/plate with and without metabolic activation. As no increase in revertant colonies was noted in any strain at any concentration,Hexadecyl 2-ethylhexanoate was considered to be not mutagenic in bacteria under the condition of this test.

In vitro cytogenicity:

There are no data available on the in vitro clastogenicity ofHexadecyl 2-ethylhexanoatein mammalian cells.In order to fulfil the standard information requirements set out in Annex VIII, 8.4.2, in accordance with Regulation (EC) No 1907/2006 Annex XI, 1.5 read-across from the structurally related analogue substance2-ethylhexyl oleateis conducted.

The structural analogue 2-ethylhexyl oleate was tested in an in vitro mammalian chromosome aberration test with cultured peripheral human lymphocytes performed in accordance to OECD guideline 473 (Buskens, 2010). 2-ethylhexyl oleate was applied at concentration of 3, 10 and 33 µg/mL (diluted in ethanol) to the cultured lymphocytes with and without metabolic activation. Both in the absence and presence of S9-mix ethylhexyl oleate did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in two independent experiments. No effects on the number of polyploid cells and no increase in cells with endoreduplicated chromosomes were observed both in the absence and presence of S9-mix. Thus, ethylhexyl oleate did not disturb mitotic processes and cell cycle progression and did not induce numerical chromosome aberrations under the experimental conditions described.

In vitro gene mutation in mammalian cells:

There are no data available on the in vitro mutagenicity ofHexadecyl 2-ethylhexanoatein mammalian cells.In order to fulfil the standard information requirements set out in Annex VIII, 8.4.3, in accordance with Regulation (EC) No 1907/2006 Annex XI, 1.5 read-across from the structurally related analogue substance2-ethylhexyl oleateis conducted.

Data on gene mutation in mammalian cells is available from a study with the structural analogue 2-ethylhexyl oleate, which was tested in a GLP study perfomed according to OECD guideline 476 (Verspeek-Rip, 2010). Mouse lymphoma L5178Y cells were treated with 2-ethylhexyl oleate(diluted in ethanol) ata concentration of 0.03, 0.1, 0.3, 1, 3, 10, 33, and 100 µg/mL for 3 or 24 h with and without metabolic activation. As result, no significant increase in the mutation frequency in the presence or absence of S9-mix was found, independent of incubation time or composition of the S9 mix. Thus, 2-ethylhexyl oleate did not induce gene mutations in mammalian cells under the condition of the test.

Conclusion

In conclusion, the available data on the genetic toxicity ofHexadecyl 2-ethylhexanoate and structural analogue substances indicate that Hexadecyl 2-ethylhexanoate is neither mutagenic nor clastogenic in vitro.

Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. No study was selected, since 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 substance and overall quality assessment (refer to the endpoint discussion for further details).

Short description of key information:
In vitro:
Gene mutation (Ames test): S. typhimurium TA 1535, TA 1537, TA 98, TA 100, and TA 102: negative with and without metabolic activation (according to OECD TG 471)
Mammalian cytogenicity (chromosome aberration): peripheral human lymphocytes: negative (OECD TG 473)
Mammalian mutagenicity (MLA): negative with and without metabolic activation (OECD TG 476)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.