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Administrative data

Key value for chemical safety assessment

Additional information

Justification for read-across

Data on the genetic toxicity of tetradecyl stearate (CAS 17661-50-6) 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 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) (Verspeek-Rip, 1998), performed according to OECD 471. S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100, and E. coli WP2 uvr A were exposed to the test substance at concentrations up to 1000 µg/plate. Precipitation was observed in the medium from 1000 µg/plate and above in all strain, with and without metabolic activation. 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 similarly to OECD 471 (Marquardt, 1995). The preincubation 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).

Genetic toxicity (cytogenicity) in mammalian cells in vitro

CAS 93803-87-3

An in vitro chromosomal aberration test was performed with 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) according to OECD 473 (Bertens, 1998). Cultured human peripheral lymphocytes were exposed to the test substance at concentrations up to 1000 µg/mL, with and without metabolic activation (S9-mix). In experiment 1, a short-term treatment (3 h) with harvest time 24 and 48 h, was performed without metabolic activation; while the 24 h treatment time with 24 h harvest time and 48 h treatment time with 48 h harvest time, respectively, was done with metabolic activation. In experiment 2, both the 3 h treatment with metabolic activation and the 24 h treatment without metabolic activation had a harvest time of 24 h. 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 81-113% and with metabolic activation 68-108%, compared with the vehicle control. No cytotoxicity was noted at any concentrations, but precipitation was observed at concentrations from 1000 µg/mL and above. The vehicle and positive controls were valid.

CAS 3687-45-4

The potential of oleyl oleate (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 oleyl oleate 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.

Genetic toxicity (mutagenicity) in mammalian cells in vitro

CAS 3687-45-4

An in vitro mammalian cell gene mutation assay was performed using oleyl oleate (CAS 3687-45-4), according to OECD 476 (Poth, 1994). Chinese hamster lung fibroblasts (V79) were treated with oleyl oleate 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.

 

Overall conclusion for genetic toxicity

There are no available studies on the genetic toxicity of the target substance tetradecyl stearate. 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, tetradecyl stearate 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 E.coli WP2 uvr A.
Chromosome aberration (OECD 473): negative in human peripheral lymphocytes cells and in Chinese hamster lung fibroblasts (V79) with and without metabolic activation.
Gene mutation in mammalian cells (OECD 476): negative in Chinese hamster lung fibroblasts (V79) 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 tetradecyl stearate (CAS 17661-50-6) 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.