D-Glucopyranose, oligomers, branched and linear C9-11-alkyl glycosides

Endpoint summary

Additional information

There is only limited data available on the genetic toxicity of D-Glucopyranose, oligomers, branched and linear C9-11-alkyl glycosides. 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, read-across from structurally related substances is conducted.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Sections 7.1 and 13).

In vitro

For genetic toxicity in vitro, two studies on gene mutation in bacteria are available for D-Glucopyranose, oligomers, branched and linear C9-11-alkyl glycosides (CAS 157707-87-4). However, no studies on the induction of genetic mutation and chromosome aberration in mammalian cells exist for this substance. To cover these endpoints, results of studies on the category members D-Glucopyranose, oligomers, decyl octyl glycosides (CAS 68515-73-1) and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides were used based on the category approach.

- Gene mutation in bacteria

A bacterial gene mutation assay (Ames test) was conducted with D-Glucopyranose, oligomers, branched and linear C9-11-alkyl glycosides in compliance with OECD guideline 471 and under GLP conditions (BML, 1989). In two series of experiments, the test substance at concentrations ranging from 20 to 5000 µg/plate did not induce mutations in bacteria in the absence and presence of metabolic activation in the selected strains of Salmonella typhimurium (TA 98, TA 100, TA 1535 and TA 1537) and Escherichia coli (WP2 uvrA).

In another study according to OECD 471 using the same strains of bacteria, negative results for gene mutation were obtained after treatment with the test substance at concentrations ranging from 5-625 µg/plate (Kao Corporation, 1988).

- Gene mutation in mammalian cells

The genotoxic potential of D-Glucopyranose, oligomers, decyl octyl glycosides was assessed using a gene mutation assay in cultured mammalian cells (mouse lymphoma L5178Y cells), which was equivalent or similar to OECD guideline 476 and in compliance with GLP (Microbiological Associates, 1991). Based on a preliminary toxicity study, ten doses of the non-activated and the activated cultures were selected for cloning. In the first experiment, the non-activated cultures that were cloned were treated with test substance concentrations ranging from 7.5 to101 µg/mL, whereas activated cultures were treated with concentrations ranging from 13 to 179 µg/mL. In a second experiment, the activated cultures that were cloned were treated with 161-234 µg/mL of the test substance. No increase in mutant frequency was observed at any of the concentrations tested in both experiments. Therefore, it was concluded that under the conditions used in the study, the test material was not mutagenic at the TK-locus of mouse lymphoma L5178Y cells in the absence and presence of metabolic activation.

- Chromosome aberrations

D-Glucopyranose, oligomeric, C10-16-alkyl glycosides was assayed in an in vitro mammalian chromosome aberration test conducted according to OECD guideline 473 and in compliance with GLP (Henkel, 1995). In this experiment, Chinese hamster lung fibroblasts (V79) were treated with the test substance at concentrations up to 160 µg/mL. Continuous treatment for 4 h was performed with and without S9-mix followed by culture periods of 7, 20 and 28 h. For chromosome analysis, concentrations ranging from 2 to 80 µg/mL were selected. The test substance did not induce chromosomal aberrations at any of the concentrations tested, neither in the presence nor absence of metabolic activation. Under the conditions of this assay, the test substance did not show clastogenic activity in vitro.

In vivo

No data are available on the genetic toxicity of D-Glucopyranose, oligomers, branched and linear C9-11-alkyl glycosides (CAS 157707-87-4) in vivo. However, reliable data are available for the category member D-Glucopyranose, oligomeric, C10-16-alkyl glycosides.

The category member D-Glucopyranose, oligomeric, C10-16-alkyl glycosides was tested in an in vivo Mammalian Erythrocyte Micronucleus test according to OECD guideline 474 and in compliance with GLP (SafePharm, 2000). In this micronucleus assay, 7 male mice per group were intraperitoneally administered with the test substance at 62.5, 125 and 250 mg/kg bw or the vehicle distilled water. After a 24 or 48-h period, bone marrow was extracted and polychromatic and normochromatic erythrocytes were scored for the presence of miocronuclei. No biologically relevant increase in the frequency of micronucleated polychromatic erythrocytes was observed within the treatment groups. Thus, the test substance was considered to be non-mutagenic in vivo under the conditions of this Mammalian Erythrocyte Micronucleus test.

Based on the negative results of the available studies with the test substance and the category members with alkyl chain lengths ranging from C10 to C16, it may be concluded that D-Glucopyranose, oligomers, branched and linear C9-11-alkyl glycosides does not induce genetic toxicity in vitro and in vivo.

Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted based on two Ames tests with the substance itself and by means of read-across based on a category approach with structurally related substances according to the criteria laid down in Annex XI, 1.5 of Regulation (EC) No 1907/2006. The substances of the Category are generated by the reaction of D-glucose with alcohols of varying chain length and share identical structural characteristics only differing by the alkyl chain length of the respective alcohol and varying degree of oligomerisation. Upon hydrolysis they are degraded into glucose and fatty alcohols again which can be further metabolised by common endogenous pathways like glycolysis and, in case of the alcohols, degraded in the endogenous pathway of beta-oxidation subsequently to their oxidation into fatty acids. No specific study was selected, since three different endpoints are addressed by genetic toxicity in vitro: mutagenicity in bacteria, chromosomal aberration in mammalian cells and mutagenicity in mammalian cells; genetic toxicity in vivo is no mandatory endpoint according to Regulation (EC) No 1907/2006. However, all available in vitro and in vivo 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:
In vitro:
OECD 471 (Ames): negative
RA-C, OECD 476 (Mouse lymphoma assay): negative
RA-C, OECD 473 (Chromosome aberration): negative

In vivo:
RA-C, OECD 474 (Micronucleus test in mice): negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity of D-Glucopyranose, oligomers, branched and linear C9-11-alkyl glycosides and structurally related substances according to the criteria laid down in Regulation (EC) No 1907/2006, Annex XI, 1.5 do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC. Therefore, the substance D-Glucopyranose, oligomers, branched and linear C9-11-alkyl glycosides is not expected to exert genetic toxicity, either, and data is thus conclusive but not sufficient for classification.