Octadecanoic acid, C16-20-branched alkyl esters

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro gene mutation in bacteria (Ames test, OECD 471): negative with and without metabolic activation in S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 1538, and in E. coli WP2 uvrA

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Analogue justification

No data on the genetic toxicity of octadecanoic acid, C16-20-branched alkyl esters are 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 the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Genetic toxicity (mutagenicity) in bacteria in vitro

CAS 93803-87-3

The in vitro genetic toxicity of 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) was assessed in a bacterial reverse mutation assay (Ames test), performed according to OECD 471 and in compliance with GLP (key study, 1998). S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100, and E. coli WP2 uvrA were exposed to the test substance at concentrations up to 1000 µg/plate (TA 1535, TA 98 and TA 1537) and 5000 µg/plate (TA 100 and E.coli WP2 uvrA), using the plate incorporation method in two independent experiments. Precipitation was observed in the medium at 1000 µg/plate and above in all strains, with and without metabolic activation. The positive and solvent controls were shown to be valid. The test substance did not induce reversions in the S. typhimurium strains or E. coli strain, with or without metabolic activation.

CAS 3234-85-3

The in vitro genetic toxicity of Tetradecanoic acid, tetradecyl ester (CAS 3234-85-3) was assessed in a bacterial reverse mutation assay (Ames test) performed with a protocol similar to OECD 471 (supporting study, 1994). The preincubation method was applied using S. typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 1538 in two independent experiments. Precipitation was observed in the range-finding study from 10 µg/plate for TA 98 and TA 100, and more than 50% cytotoxicity was observed in the range-finding study with TA 98 from 10 µg/plate (without metabolic activation) and with TA 100 from 1000 µg/plate (without metabolic activation). Due to the effects noted in the range-finding study, the concentration ranges tested in the main study varied per strain. The concentration ranges in the main study were: 0.1 - 10 µg/plate (TA 100, TA 1535 and TA 1538) and 0.05 – 5 µg/plate (TA 98 and TA 1537) without metabolic activation; and 10 – 1000 µg/plate (TA 100, TA 1535 and TA 1538) and 1 - 640 µg/plate (TA 98 and TA 1537) with metabolic activation. The positive and solvent controls were shown to be valid. The test substance did not induce reversions in any of the S. typhimurium strains with or without metabolic activation.

 

CAS 95912-86-0

A bacterial reverse mutation assay (Ames test) was performed to assess the potential in-vitro genetic toxicity of Fatty acids, C8-10, C12-18 alkyl esters (CAS 95912-86-0) (supporting study, 1989). The study was performed according to OECD guideline 471 and under GLP conditions, but without the currently 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. Both the positive and the solvent controls were shown to be valid. Cytotoxicity was observed at 5000 µg/plate, with and without metabolic activation. The test substance did not induce an increase in reversions in any of the S. typhimurium strains with or without metabolic activation.

Overall conclusion for genetic toxicity

There are no available studies on the genetic toxicity of the target substance.Therefore, analogue read-across from source substances was applied fromin vitro studies on gene mutations in bacterial cells. The results of the available in vitro studies were consistently negative. Based on the available data and following the analogue approach, octadecanoic acid, C16-20-branched alkyl esters is not expected to be mutagenic in vitro.

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 octadecanoic acid, C16-20-branched alkyl esters, 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.

 

The available Ames tests on source substances fulfil the standard information requirements given in Annex VII of Regulation (EC) 1272/2008 and are suitable for classification. Based on the analogue read-across approach, there is no indication that the target substance induces genetic toxicity. Nevertheless, no final decision on classification for genetic toxicity according to Regulation (EC) 1272/2008 can be made, as no information on mutagenicity and clastogenicity in mammalian cells/in vivo of read-across substances have been considered in the Annex VII dossier for octadecanoic acid, C16-20-branched alkyl esters.