2-octyldodecyl myristate

Endpoint summary

Additional information

Justification for read-across

Data on the in vitro genetic toxicity in mammalian cells of 2-octyldodecyl myristate (CAS 22766-83-2) are not available. The genetic toxicity assessment was therefore partly 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 22766-83-2

The in vitro genetic toxicity of 2-octyldodecyl myristate (CAS 22766-83-2) was assessed in a bacterial reverse mutation assay (Ames test) (Merediz, 2007). The study was performed according to OECD Guideline 471 and under GLP conditions. The plate incorporation method was applied in the first experiment and the preincubation method in the second experiment, using S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100, and E. coli WP2 uvrA pKM 101. All the strains were tested at concentrations up to the limit value of 5 µL/plate. The test substance did not induce an increase in reversions in the S. typhimurium and E.coli strains, with or without metabolic activation. No cytotoxicity was observed, with and without metabolic activation. The controls were valid.

 

Genetic toxicity (cytogenicity) in mammalian cells in vitro

CAS 93803-87-3

The cytogenetic potential of 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) was assessed in an in vitro mammalian chromosome aberration test in primary human lymphocytes, performed according to OECD Guideline 473 and under GLP conditions (Bertens, 1998). Duplicate cultures of cultured human peripheral lymphocytes were evaluated for chromosome aberrations in the presence and absence of metabolic activation. In the first experiment, cells were incubated with test substance concentrations of 100, 333 and 1000 µg/mL for 24 hours with a 24-hour fixation time and at 1000 µg/mL for 48 hours with a 48-hour fixation time, in the absence of a metabolic activation system. The first experiment was also performed with cells exposed to 100, 333 and 1000 µg/mL for 3 hours with a 24-hour fixation time and at 1000 µg/mL for 3 hours with a 48-hour fixation time in the presence of metabolic activation. In the second experiment cells were incubated with 100, 333 and 1000 µg/mL for 24 hours followed by a 24-hour expression time, without metabolic activation. In the presence of metabolic activation cell were exposed to 100, 333 and 1000 µg/mL for 3 hours followed by a 24-hour expression time. No cytotoxicity was observed. At 1000 µg/mL, precipitation was observed in the culture medium. The vehicle (solvent) and positive controls were shown to be valid. The test material did not induce a statistically significant increase in the frequency of cells with chromosome aberrations, with or without metabolic activation.

CAS 3687-45-4

The potential of oleyl oleate (CAS 3687-45-4) to induce chromosomal aberrations was assessed using Chinese hamster lung fibroblast (V79) cells, in a study performed according to OECD 473 and under GLP conditions (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. A 4-hour treatment was performed without metabolic activation, using 10, 60 and 100 µg/mL concentration levels with an 18-hour fixation time and a 100 µg/mL concentration level with a 28-hour fixation time. The treatment with metabolic activation was performed at concentrations of 10, 60 and 100 µg/mL with an 18-hour treatment time, and 18-hour fixation time and at 100 µg/mL with a 28-hour treatment time and 28-hour 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. 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, according to OECD 476 and under GLP conditions (Poth, 1994). Two separate experiments were performed. Chinese hamster lung fibroblast (V79) cells were treated with oleyl oleate at concentrations of up to 100 µg/mL for 4 hours, 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. Precipitation was seen at concentrations of 100 µg/mL and higher. The positive and negative controls were valid and within the range of historical control data. No cytotoxicity was observed. No significant increase in mutation frequency was observed, with and without metabolic activation.

Overall conclusion for genetic toxicity

The result of the in vitro study on genetic toxicity in bacterial cells was negative. There are no available studies on the in vitro genetic toxicity in mammalian cells of the target substance 2-octyldodecyl myristate.Therefore analogue read-across from source substances was applied from in vitro studies on cytogenicity and gene mutation in mammalian cells, using 2 source substances. The results of the available in vitro studies on source substances were negative. Based on the available data on target and source substances, and following the analogue approach, 2-octyldodecyl myristate 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 and TA 98 and in E. coli WP2 uvrA pKM 101
Chromosome aberration (OECD 473): negative in primary human lymphocytes cells and 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 2-octyldodecyl myristate (CAS 22766-83-2), 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.