Alcohols, C16-18, reaction products with D-glucose

Endpoint summary

Additional information

There is only limited data available on the genetic toxicity of D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess). 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, one key study on gene mutation in bacteria is available for D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess) (30% C16/C18-APG and 70% C16/C18 fatty alcohols). Further studies on gene mutation in bacteria with hexadecan-1-ol (CAS 36653-82-4), octadecan-1-ol (CAS 112-92-5) and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides are available. However, no studies on the induction of genetic mutation in mammalian cells and chromosome aberration exist for D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess). 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 for read-across based on the category approach.

- Gene mutation in bacteria

A bacterial gene mutation assay (Ames test) was conducted with D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess) in compliance with OECD guideline 471 and under GLP conditions (Henkel, 1993). In two series of experiments, the test substance at concentrations ranging from 8 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, TA 1537 and TA 1538).

The Ames tests performed with the fatty alcohols hexadecan-1-ol and octadecan-1-ol, which comprise 50% of the substance to be registered, did not result in any effects on the mutagenicity of the same strains of Salmonella typhimurium at concentrations up to 5000 µg/plate (SafePharm, 1996 and 1996).

Consistent with this, an Ames test investigating the effects of the category member D-Glucopyranose, oligomeric, C10-16-alkyl glycosides in Salmonella and E.coli strains 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 properties of D-Glucopyranose, oligomeric, C10-16-alkyl glycosides were further confirmed (Henkel, 1988 and 1994).

- Gene mutation in mammalian cells

The genotoxic potential of D-Glucopyranose, oligomers, decyl octyl glycosidess 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 GLP (Henkel, 1995). In this experiment, Chinese hamster lung fibroblasts (V79) were treated with the test substance at concentrations up to 160 µg/mL in the presence of metabolic activation and up to 16 µg/mL without. 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, either 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

No studies are available investigating the genetic toxicity of D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess) in vivo. Thus, studies performed with the structurally related substances octadecan-1-ol (CAS 112-92-5) and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides were used to cover this endpoint based on analogue and category approach.

The structurally related substance octadecan-1-ol, was tested in an in vivo Mammalian Erythrocyte Micronucleus test according to OECD guideline 474 and in compliance with GLP (Hachiya et al., 1982). In this micronucleus assay, 6 male mice were orally administered with single doses of 360, 730, 1450 mg/kg bw of the test substance by gavage. Further 5 animals received 4 repeated doses of the test substance at 730 mg/kg bw over a period of 24 h. The control group was treated with olive oil as vehicle. After a post-exposure period of 24 h (single treatment) or 5 days (repeated administration), no significant increase in the number of micronucleated erythrocytes was observed in any treatment group. Under the conditions of this assay, the test substance was considered to be not clastogenic in mice in vivo.

In a further Mammalian Erythrocyte Micronucleus assay with the category member D-Glucopyranose, oligomeric, C10-16-alkyl glycosides according to OECD guideline 474 and in compliance with GLP, 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 (SafePharm, 2000). After a 24 or 48-h period, 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 not clastogenic in mice in vivo under the conditions of this Mammalian Erythrocyte Micronucleus assay.

Based on the negative results of the available studies on the alkyl glucosides and fatty alcohols it may be concluded that D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess) does not induce genetic toxicity in vitro and in vivo, either.

Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted based on an Ames test 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: not mutagenic with and without metabolic activation (no cross-linking strains tested)
RA-C, OECD 473, CA: not genotoxic with and without metabolic activation
RA-C, OECD 476, MoLy: not mutagenic with and without metabolic activation
In vivo:
RA-C, OECD 474: not genotoxic with and without metabolic activation

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity of D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess) and structurally related substances according to 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, and are therefore conclusive but not sufficient for classification.