Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

There is no data available on the genetic toxicity of Reaction products of D-Glucose, n-Butanol and C10-12 (even numbered) alcohols. 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, data on substances which share a strong structural relationship with Reaction products of D-Glucose, n-Butanol and alcohols, C10-12 (even numbered) exist. Based on the category approach, the results of 6 studies on genetic toxicity in vitro of the category members D-Glucopyranose, oligomers, hexyl glycosides, D-Glucopyranose, oligomers, decyl octyl glycosides (CAS 68515-73-1) and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides were used for read-across.

- Gene mutation in bacteria

A bacterial gene mutation assay (Ames test) was conducted with D-Glucopyranose, oligomers, hexyl glycosides in compliance with OECD guideline 471 and under GLP conditions (SafePharm, 1998). In two series of experiments, the test substance at concentrations ranging from 50 to 5000 µg/plate did not induce mutations in the Ames test 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). Consistent with this, an Ames test investigating the effects of D-Glucopyranose, oligomeric, C10-16-alkyl glycosides in the same strains of bacteria showed negative results on mutagenicity up to concentrations of 5000 µg/plate (SafePharm, 2000). In two further studies only performed in Salmonella strains, the non-mutagenic potential of D-Glucopyranose, oligomeric, C10-16-alkyl glycosides was further confirmed (Henkel, 1988 and 1994).

- Gene mutation in mammalian cells

The genotoxic potential of D-Glucopyranose, oligomers, decyl octyl glycosides (CAS 68515 -73 -1) 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, respectively. 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, both in the presence or absence of metabolic activation. Under the conditions of this assay, the test substance did not show clastogenic activity in vitro.

In vivo

The category member D-Glucopyranose, oligomeric, C10-16-alkyl glycosides was further 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 distilled water as vehicle. After a 24 or 48-h period, bone marrow was extracted and polychromatic and normochromatic erythrocytes were scored for the presence of micronuclei. 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 on category members with alkyl chain lengths ranging from C6 to C16, it may be concluded that Reaction products of D-Glucose, n-Butanol and alcohols, C10-12 (even numbered) do not induce genetic toxicity in vitro and in vivo.

Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by 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:
RA-C, 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 substances structurally related to Reaction products of D-Glucose, n-Butanol and C10-12 (even numbered) alcohols 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, Reaction products of D-Glucose, n-Butanol and C10-12 (even numbered) alcohols is not considered to exert genetic toxicity, either, and the data are thus conclusive but not sufficient for classification.