Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Bacterial reverse mutation assay (Ames / OECD guideline 471): negative

In vitro mammalian chromosomal aberration assay (ChrAb / OECD guideline 473): negative

In vitro mammalian cell gene mutation assay (MLA / OECD guideline 476): negative

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

To cover the endpoint genotoxicity of substance (Z)-9-Octadecen-1-ol, ethoxylated, < 2.5 EO (CAS 9004-98-2), studies from C16-18AE (CAS 68439-49-6) and C18AE (CAS 9005-00-9) were taken for read-across.

Read-across is justified because the structure of alcohol ethoxylates (AE) is not of concern for potential genotoxicity. In addition, in all available in-vitro and in-vivo genotoxicity assays, there was no indication of genetic toxicity of a broad range of structurally different AE (HERA, 2009). As no indication of genotoxicity was observed for different AEs, the length of the alkyl chain as well as the grade of ethoxylation does not exert any meaningful influence on genotoxicity, further supporting the read-across.

 

Mutagenicity in bacteria was assessed in two studies performed according or equivalent to OECD Guideline 471. In the study (reliability 4, Croda, 1995)) with C18AE (CAS 9005-00-9) Salmonella typhimurium strains TA 98 and TA100 were treated using the plate incorporation method as well as the preincubation method, both with and without the addition of a rat liver S9-mix. A reproducible mutagenic activity of the test material to any of the tester strains was not observed with and without metabolic activation. Thus, under the conditions of this test the test substance can be regarded as not mutagenic in bacteria.

 

In the second study (Sasol, 1997), Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 were treated with C16-18AE (CAS 68439-49-6) using the plate incorporation method as well as the preincubation method, both with and without the addition of a rat liver S9-mix. The dose ranges were for the plate incorporation test were 50, 160, 500, 1600 and 5000 µg/plate; for the first preincubation test 50, 150, 300, 900 and 1500 µg/plate and for the second one 10, 25, 50, 100 and 150 µg/plate. All tests were done in triplicates. The vehicle (acetone) and negative (untreated) control plates produced counts of revertant colonies within an acceptable range. All positive controls used in the test induced marked increases in the frequency of revertant colonies, both with and without the metabolising system. A reproducible mutagenic activity of the test material to any of the tester strains was not observed with and without metabolic metabolic activation. Thus, under the conditions of this test the test substance can be regarded as not mutagenic in bacteria.

 

The clastogenic potential was assessed in a chromosomal aberration test with C16-18AE (CAS 68439-49-6) in mammalian cells according to OECD Guideline 473 (Sasol, 1995b). Chinese hamster ovary cells (CHO) were exposed to 313, 625, 1250, 2500 and 5000 µg/mL in the presence and 1.25, 2.5, 5, 10, 20, 39 and 78 µg/mL in the absence of metabolic activation. Positive and vehicle (1% ethanol) control cultures were included in each assay. No increases in the number of chromosome aberrations in the presence or absence of metabolic activation were seen at any concentration tested. Appropriate reference mutagens used as positive controls showed a significant increase in chromosome aberrations, thus indicating the sensitivity of the assay, and the efficacy of the S9-mix. Hence, the test substance can not be regarded as clastogenic.

 

The mutagenic potential in mammalian cells was assessed with C16-18AE (CAS 68439-49-6) by a HPRT-assay according to OECD Guideline 476 (Sasol, 1995c). Following pre-tests with the concentration ranging from 1-100 µg/mL, the latter being the solubility limit of the test substance, Chinese hamster ovary cells were exposed for 4 h to concentrations of 1.8, 6, 18, 60 and 100 µg/mL in the absence and presence of metabolic activation by rat liver S9-mix. No dose-related increases in mutant colony numbers were obtained in two independent experiments with the test substance in either the presence or absence of S9-mix. Appropriate reference mutagens used as positive controls produced highly significant increases in mutation frequency, thus indicating the sensitivity of the assay. Therefore, the test substance is regarded as not mutagenic in mammalian cells.

 

In conclusion, (Z)-9-Octadecen-1-ol, ethoxylated, < 2.5 EO (CAS 9004-98-2) is regarded as non-genotoxic.

Justification for classification or non-classification

According to the classification criteria of Regulation (EC) No. 1272/2008 the substance does not need to be classified for genotoxicity.