Fatty acids, C14-18, C14-18-alkyl esters

Endpoint summary

Additional information

Justification for read-across

There are only limited data available on the genetic toxicity of fatty acids, C14-18, C14-18-alkyl esters(CAS 85566-24-1). In order to fulfil the standard information requirements set out in Annex VII and VIII, 8.4, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006,

ead-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 to avoid the need to test every substance for every endpoint).

The target substance and all source substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information on the source substances is used to predict comparable results for the target substance fatty acids, C14-18, C14-18-alkyl esters (CAS 85566-24-1).

The target substance is characterized as an UVCB substance comprised of esters of mainly C14 fatty acid/C14 alcohol, C16 fatty acid/C14 alcohol and C16 fatty acid/C16 alcohol substances. The three source substances are structurally similar to the target substance: Fatty acids, C8-10, C12-18-alkyl esters (CAS 95912-86-0) is a UVCB substance consisting of C8-C10 fatty acids esterified with C12-C18 alcohol. Tetradecanoic acid, tetradecyl ester (CAS 3234-85-3) is a mono-constituent substance of a C14 fatty acid esterified with C14 alcohol. 9-Octadecenoic acid(Z)-, 9-octadecenyl ester, (Z)- (CAS 3687-45-4) is a mono-constituent substance consisting of C18:1 oleic acids esterified with C18:1 alcohol. Thus, target and source substance contain similar structural properties based on common functional groups.

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

Discussion

 

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 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 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. All the positive controls were valid.

 

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 similarly to OECD 471, but without the required TA 102 or E. coli strain (Marquardt, 1995). The pre-incubation method was applied using S. typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 1538 at concentrations up to 1000 µg/plate. No TA 102 or E. coli strain was used. The test substance did not induce reversions in any of the S. typhimurium strains with or without metabolic activation. All the positive controls were valid. Precipitation was observed at the highest dose level in the range-finding study with TA 98 and TA 100. 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).

 

CAS 3687-45-4

 

The potential of 9-Octadecenoic acid(Z)-, 9-octadecenyl ester, (Z)- (CAS 3687-45-4) to induce chromosomal aberrations was assessed using Chinese hamster V79 cells, in a study performed according to OECD 473 (Völkner, 1994). The V79-cells were exposed to

9-Octadecenoic acid(Z)-, 9-octadecenyl ester, (Z)- at concentrations up to 100 µg/mL, with and without metabolic activation (S9-mix). One experiment with duplicate replications was performed with short-term treatment (4 h) and fixation time 18 and 28 h, without metabolic activation; and with metabolic activation using 18 h treatment time and 18 h fixation time and 28 h treatment time and 28 h fixation time, respectively. The test material did not induce a statistically significant increase in the frequency of cells with chromosome aberrations, with or without metabolic activation. The mitotic indices of the treated cultures without metabolic activation were 83.4-119% and with metabolic activation 91-127.1%, compared with the vehicle control. Precipitation was observed at concentrations from 100 µg/mL, while no cytotoxicity was noted at any concentration. The vehicle and positive controls were valid.

 

An in vitro mammalian cell gene mutation assay was performed using 9-Octadecenoic acid(Z)-, 9-octadecenyl ester, (Z)- (CAS 3687-45-4), according to OECD TG 476 (Poth, 1994). Chinese hamster lung fibroblasts (V79) were treated with

9-Octadecenoic acid(Z)-, 9-octadecenyl ester, (Z)- at concentrations of up to 100 µg/mL for 4 h both with and without metabolic activation. After an expression time of 7 days in growth medium, cells were incubated for 9 or 12 days with 6-thioguanine as selection agent for forward mutation at the HPRT locus. Both with and without metabolic activation, no increases in mutant frequency were observed in the initial and in the confirmatory gene mutation assay. There was no evidence of excessive cytotoxicity (i.e., < 10 % relative cloning efficiency) at any of the tested concentrations either in the presence or absence of metabolic activation in any of the experiments performed. Based on these results, the test item was considered to be not mutagenic to mammalian cells under the conditions of the test.

 

 

Conclusions for Genetic toxicity

Based on read-across data, sufficient evidence is available to conclude that the substance fatty acids, C14-18, C14-18-alkyl esters (CAS 85566-24-1) is not mutagenic nor clastogenic.

 

Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by means of read-across from structural analogues. 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:
Ames test (OECD 471): negative with and without metabolic activation in S. typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 1538.

Chromosomal Aberration (OECD 473): negative in V79 cells with and without metabolic activation

Gene mutation in mammalian cells (OECD 476): negative in V79 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 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.