D-Glucopyranose, oligomeric, heptyl glycosides

Endpoint summary

Additional information

The Alkyl Polyglycosides Category contains D-Glucopyranose monomers and oligomers with fatty alcohols C4 to C18 linear or in several cases (C9 to C11) mono-branched. Structural similarities of the category substances are reflected in similar physico-chemical properties and mode of action. Alkyl polyglycosides have a common metabolic fate that involves hydrolysis of the alpha- and beta-glycosidic bond to the fatty alcohol and glucose. Glucose and glucose oligomers enter the carbohydrate metabolic pathway and are catabolised into pyruvate and subsequently to the major extent into acetyl-CoA, which is introduced into the citric acid cycle with the aim to generate reduction equivalents for energy generation in the oxidative phosphorylation. Fatty alcohols, representing the main difference in the structure of different alkyl polyglycosides, are oxidized to the corresponding fatty acid and fed into the physiological pathways of beta-oxidation, where they are also oxidised to acetyl-CoA. In addition to its function in the generation of energy by catabolic processes acetyl-CoA can also be used in anabolic processes like lipid synthesis, which is important for the storage of energy in form of large high-energy macromolecules.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met. In particular for human toxicity, environmental fate and eco-toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across)”. Therefore, the available experimental data were collected and evaluated according to Annex XI in regard to:

-      Test duration (only tests which cover the expected exposure duration were regarded as suitable)

-      Key parameters of the test (only tests that cover the key parameter were accepted as suitable)

-      Comparability of the test systems

-      The adequacy of the results for C&L

-      The documentation of the test procedures (only in case of good documentation data)

Only data that were judged to cover the requirements specified above were used as adequate data suitable for the category and its members. In this particular case the similarity of the Alkyl Polyglycosides Category members is justified, in accordance with the specifications listed in Regulation (EC) No. 1907/2006 Annex XI, 1.5 Grouping of substances and read across, on basis of scope of variability and overlapping of composition, representative molecular structure, physico-chemical properties, toxicological, ecotoxicological profiles and supported by various QSAR methods. There is no convincing evidence that any one of these respective chemicals might lie out of the overall profile of this category. The key points that the members share are:

(i)              Common origin: produced from fatty alcohols, reacting with D-glucose in the presence of an acid catalyst.

(ii)             Similar structural features: aliphatic hydrocarbon chain bound to glucose oligomers by alpha or beta glycosidic bond.

(iii)            Similar physico-chemical properties: trend in log Pow based on alkyl chain length and degree of glycosylation; low vapour pressure; water solubility decreasing with the alkyl chain length, starting from very high and high values up to insoluble C16-18; surface active substances fully dissociated in water (exception: C16-18).

(iv)           Common properties for environmental fate & eco-toxicological profile: readily biodegradable, no potential for bioaccumulation, low to moderate adsorption potential, clear trend in aquatic toxicity (increasing toxicity with increasing carbon chain with a maximum at C12-16 and then decreasing), no potential for sediment and soil toxicity.

(v)            Similar metabolic pathways: absorption in the intestine, hydrolysis of the α- and β-glycosidic bond in intestine and further metabolism of the breakdown products sugar and alcohol. Alkyl polyglycosides with α-glycosidic bond may already be hydrolysed in the saliva by enzymatic activity of α-amylases.

(vi)           Common levels and mode of human health related effects: The skin and eye irritating properties of the alkyl polyglycosides represent the main factor for effects on human health. The similar toxicokinetic behaviour (hydrolysis of the α- and β-glycosidic bonds) results in similar cleavage products, which show a low toxicity after acute and repeated oral exposure. Furthermore, all category members are not sensitising, not mutagenic or clastogenic, and have shown no reproduction and developmental toxicity.

Common origin

The synthesis of alkyl polyglycosides was discovered by the reaction of glucose and fatty alcohol in the presence of an acid catalyst. Two methods can be applied: direct synthesis and the alternative transacetalization process (Geetha and Tyagi, 2012).

Direct synthesis: it is a synthesis of fatty alcohols of varying alkyl chain length and purities of either technical or natural origin with D-Glucose; the end product is obtained using the alcohol in excess with respect to the stoichiometric value (ibid).

Alternative synthesis: a transacetalization process is applied when oligo- and polyglycoses (starch or syrups) are used. Polysaccharide is depolymerised with lower alcohols (butanol or propylene glycol) in the presence of an acid catalyst. APGs are formed when the oligoglucoside intermediate is treated with long chain alcohol in the presence of an acid catalyst (ibid).

Structural similarity

Alkyl polyglycosides are monomers or oligomers containing D-Glucopyranose rings (basically up to m = 2, minor contributions of oligomers up to 5 rings are acceptable) and fatty alkyl chains, in the C_n range from n = 4 to 18. The structural similarity is straightforward and the properties depend on the number of ringsmand the alkyl chain lengthn. The alkyl chains are linear; up to 10% mono-methyl branched (predominantly linear) species contribute to D-Glucopyranose, oligomers, branched and linear C9-11-alkyl glycosides. Another feature of this particular substance, and D-Glucopyranose, oligomeric, heptyl glycosides (C7), is that they contain odd-numbered chains, while the other chains represented in the category are even-numbered. These features are not supposed to cause exceptions from the overall assumption that the differences in properties of category members are related to the number of glucopyranose rings m and the alkyl chain lengthn.

The substance D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess) is characterised by the longest alkyl chains over the category. The exceptional character of this category member is additionally revealed in the fact that this UVCB substance contains C16 and C18 alcohol homologues. They can be described as 0-mers (m= 0). Their presence is not related to any additional chemical functionality: the influence is manifested in variability in physico-chemical parameters. In particular, the octanol-water partition coefficient is considerably higher than those observed for the rest of category members, and correspondingly, the water solubility is lower. The details are outlined in the next section and the related differences with respect to eco- and toxicological properties are discussed throughout the document.

Similar physico-chemical properties

The physico-chemical properties of alkyl polyglycosides are described below. The data are presented in Table 1.

Physical state and melting point

Substances in the Alkyl Polyglycosides Category are marketed predominantly as aqueous solutions, with an exception of the in water non-soluble D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess). The tests examining their physico-chemical properties were conducted on pure dried substances after eliminating the aqueous phase. In all cases alkyl polyglycosides were determined solid under ambient conditions. Due to the nature of these substances, it is difficult to describe their melting behaviour. Experiments performed using DSC (digital scanning calorimetry) resulted mostly in estimations revealing decomposition of the substances at relatively high temperatures (> 150 °C; cf. Table 1). For two substances, D-Glucopyranose, oligomers, branched and linear C9-11-alkyl glycosides, and D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess), the melting point is determined precisely (115 °C vs. 65 °C, respectively), however the methods applied are different (capillary method vs. DSC, respectively). With respect to the differences of the methods applied, any clear trends cannot be observed. The common property over the category is the solidity of all members at ambient conditions.

Boiling point

DSC diagrams of alkyl polyglycosides show that category members boil and/or decompose at high temperatures reaching ca. 300 °C (cf. Table 1). The decomposition often occurs already during melting. The data reveal that alkyl polyglycosides are non-volatile (Vapour pressure).

Density

Relative densities of alkyl polyglycosides were measured in the range of 0.97-1.34.

Vapour pressure

Alkyl polyglycosides are non-volatile and they do not partition into the air. The vapour pressures were determined experimentally in the range of ca. 1E-07 – 1E-03 Pa. For two substances, D-Glucopyranose, oligomeric, C10-16-alkyl glycosides, and D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess), it was difficult to determine the vapour pressures experimentally and the calculation approach (Grain-Watson method) was applied. For solid substances this approach is based on the lowest possible melting and boiling temperatures. The calculated values up to ca. 1E-02 Pa (Table 1) should be interpreted as the highest possible ones.

Octanol-water partition coefficient (log P_ow)

The accurate determination of log P_owis very difficult for surface-active substances. Surfactants tend to concentrate at hydrophilic/hydrophobic boundaries rather than to equilibrate between phases. Therefore, P_owis not a good descriptor of surfactant hydrophobicity and only of limited predictive value for the partitioning of these compounds in the environment (Könnecker et al, 2011).

The determinations of partition coefficients for the category substances were performed using different methods resulting in low values < 3 (exception: D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess)), but hardly showing a trend. While the HPLC method used for D-Glucopyranose, oligomers, hexyl glycosides results in log Pow > 1.7, and the shake flask method used for D-Glucopyranose, oligomeric heptyl glycosides in log Pow = -1.3, the calculations employing solubilities in n-octanol and water lead to the values of -1.53 (D-Glucopyranose, oligomers, branched and linear C9-11-alkyl glycosides) and -0.07 (D-Glucopyranose, oligomeric, C10-16-alkyl glycosides). In addition to these determinations, calculations were performed with KOWWIN v1.68. The calculated partition coefficient of homologues depends on the number of ringsmand the alkyl chain lengthn. While each CH₂-group added to the chain increases log P_owby ca. 1 logarithmic unit, each glucopyranose ring decreases the coefficient by ca. 2.5 logarithmic units. In Table 3, data matrix 1, Sec. 3 the highest calculated values are given (m= 1 or 0 for C16-18;n= maximal length present in the substance). The calculated values appear to describe the partition coefficient in a more satisfactory way with respect to the ones reported from different experiments. In particular, the high value obtained for D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess) is in agreement with the measured low water solubility of this substance (cf. Sec. 2.3.6). Each of the experimental methods used has its limitations, and the results should be viewed and interpreted with caution, also because the proportions of homologues with different ring numbers and chain lengths (mandnvalues, respectively) may vary, what influences the overall result.

Water solubility

As in the case of other physico-chemical properties, also water solubility is difficult for experimental determination in the case of surface active substances. In particular, such phenomenon as micelle formation is observed (Könnecker et al, 2011). Experimental determinations employing flask method lead in most cases to the observation that the substance is miscible in any proportions with water and only the estimated value (“not less than…”) can be given as a quantitative measure of water solubility. Typical orders of magnitude are hundreds of g/L. The exceptional case is again D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess), exhibiting water solubility lower than 0.05 mg/L. This is related to the fact that the alkyl chains in this case are the longest (n= 16, 18; usually in chain-length based chemical categories water solubility decreases with the chain length), but even to more extent that alcohols C16 and C18, non-soluble in water (m= 0) contribute significantly to the composition. The exceptional features of this substance (high log P_ow, low water solubility) can be thus predicted on the basis of the molecular structure and trends observed in the category: the substance can be viewed as category member, but its different properties must be treated with special care. All category substances do not dissociate in water, because of a lack of dissociable groups.

Surface tension

Alkyl polyglycosides are surfactants, and their surface tension is considerably lower than the one of water at room temperature – 72 mN/m. The measured values for the category members are between 27 and 64 mN/m – see Table 1. Since 6 of 7 substances are well soluble in water, in all cases the concentration of 1 g/L was submitted to experiment. Only compound D-Glucopyranose, oligomers, butyl glycosides fails to fulfil the criterion: surface tension < 60 mN/m, for a substance to be characterized as surface active. The substance D-glucose, reaction products with alcohols C16-18 (even numbered) (excess), as the one insoluble in water, is exempted from the surface tension testing.

Flammability

6 of 7 substances are experimentally determined to be non-flammable (EU test A.10 – flammability solids). Data for D-Glucopyranose, oligomers, decyl octyl glycosides is not available, so the category read-across is applied in this case. Flammability on contact with water and pyrophoric properties are excluded based on the molecular structure of all homologues involved.

Summary

A summary of physico-chemical properties is provided in Table 1. As UVCB substances are derived from natural sources with highly variable compositions, some measures of physico-chemical properties are inapplicable or not accurate enough for a trend analysis.

The physico-chemical properties of the category members were determined similar over the category at least for shorter chain (n< 16) and not alcohol-containing (m> 0) members. Properties of D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess) are different especially in regard to partition coefficient and water solubility. For a number of endpoints the experimental values for surface active substances could be only estimated and wherever possible were supported by valid QSAR calculations.

Table 1Physico-chemical properties – data matrix 1 (*)

ID No.

Substance

CAS No.

Appearance; melting point/ melting range

Boiling point

Relative Density at 20 °C

Vapour pressure at 20 °C

Octanol-water partition coefficient, log Pow (**)

Water solubility at 20 °C

Surface tension, c= ca. 1 g/L

Flammability

# 1

D-Glucopyranose, oligomeric, butyl glycoside

-

ER: solid; 225 °C (decomp.)

ER: ca. 225 °C (decomp.) at ca. 1013 hPa

ER: 1.34

ER: 1.4E-05 Pa

Calc: -0.91 QSAR: -1.03 (C4)

ER: > 1000 g/L

ER: 64.1 mN/m at 20 °C

ER: non flammable

# 2

D-Glucopyranose, oligomers, hexyl glycosides

-

ER: solid; > 300 °C (decomp. possible)

ER: > 300 °C (decomp. possible) at ca. 1013 hPa

ER: 1.18

ER: 1.5E-03 Pa

ER: 1.72-1.77 QSAR: -0.05 (C6)

ER: 750 g/L

ER: 33.9-35.5 mN/m at 24 °C

ER: non flammable

# 3

D-Glucopyranose, oligomeric, heptyl glycoside

-

ER: solid; 250-275 °C (decomp.)

ER: 250-275 °C (decomp. already during melting) at ca. 1013 hPa

ER: 0.976

ER: 7.2E-06 Pa

ER: -1.3 QSAR: 0.44 (C7)

ER: > 1000 g/L at 20.55 °C

ER: 30.5 mN/m at 20 °C

ER: non flammable

# 4

D-Glucopyranose, oligomers, decyl octyl glycosides

68515-73-1

ER: solid; RA from D-Glucopyranose, oligomers, hexyl glycosides and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides : > 150 °C

RA from D-Glucopyranose, oligomers, hexyl glycosides and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides : > 300 °C at ca. 1013 hPa

RA from D-Glucopyranose, oligomers, hexyl glycosides and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides : 1.16-1.18

RA from D-Glucopyranose, oligomers, hexyl glycosides and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides : < 1.0E-02 Pa

RA from D-Glucopyranose, oligomers, hexyl glycosides and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides : < 1.77 QSAR: 1.92 (C10)

RA from D-Glucopyranose, oligomers, hexyl glycosides and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides : > 200 g/L

RA from D-Glucopyranose, oligomers, hexyl glycosides and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides : 29-36 mN/m

RA from D-Glucopyranose, oligomers, hexyl glycosides and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides : non flammable

# 5

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

157707-87-4

ER: solid; 115 °C

ER: ca. 335 °C (boiling and/or decomp.) at 989 hPa

ER: 1.19

ER: 4E-03 Pa

Calc: -1.53 QSAR: 2.33 (C11)

ER: > 500 g/L

ER: 27.6 mN/m at 20 °C

ER: non flammable

# 6

Reaction products of D-Glucose, n-Butanol and alcohols C10-12 (even numbered)

-

ER: solid; > 200 °C (decomp. at 250 °C)

ER: 250 °C (decomp.) at ca. 1013 hPa

ER: 1.29

ER: 1E-04 Pa

RA from D-Glucopyranose, oligomeric, butyl glycosides and D-Glucopyranose, oligomeric, C10-16-alkyl glycosides : ≤ -0.07 QSAR: 2.90 (C12)

ER: > 900 g/L at 23 °C

ER: 27 mN/m at 20 °C

ER: non flammable

# 7

D-Glucopyranose, oligomeric, C10-16-alkyl glycosides

D-Glucopyranose, oligomeric, C10-16-alkyl glycosides

ER: solid; > 150 °C (decomp. possible)

ER: > 301 °C (boiling and/or decomp.) at ca. 1013 hPa

ER: 1.16

Calc: ≤ 7.7E-03 Pa

Calc: < -0.07 QSAR: 3.88 (C14)

ER: > 200 g/L

ER: 29.5 mN/m at 23 °C

ER: non flammable

# 8

D-Glucose, reaction products with alcohols C16-18 (even numbered) (excess)

-

ER: solid; 65 °C

ER: ca. 314 °C (boiling and/or decomp.) at 1004 hPa

ER: 1.03

Calc.: ≤ 4.2E-02 Pa

Calc.: > 6.03 QSAR: 7.72 (C18 alc.)

ER: < 0.05 mg/L

Too low water solubility

ER: non flammable

# 9

Hexadecan-1-ol (a)

36653-82-4

ER: solid; 51 °C (pour point)

ER: 319 °C at 1013 hPa

ER: 0.89 at 16 °C

ER: 0.3 Pa at 38 °C

ER: 6.7

ER: < 1 mg/L at 23 °C

Too low water solubility

-

# 10

Octadecan-1-ol (a)

112-92-5

ER: solid; 57 °C (pour point)

ER: 335 °C at ca. 1013 hPa

ER: 0.91

ER: 0.1 Pa at 38 °C

ER: 7.4

ER: < 1 mg/L at 23 °C

Too low water solubility

-

 

Abbreviations:

ER - experimental result

RA – read across

WoE – weight of evidence

QSAR - Quantitative Structure–Activity Relationships

ES – expert statement (based on category data)

 

(*) substances #2, 4 and 7 were registered in 2010, substances #1, 5, 6 and 8 were registered in 2013; substance #3 is scheduled for registration under Regulation (EC) No 1907/2006 (REACH) in 2014/2015.

(**) QSAR calculations: EPISUITE KOWWIN v1.68, the highest obtained value – for monomer (C16-18: alcohol) and the longest chain represented.

(a) Surrogate substances: fatty alcohols. Available data on these substances are used for assessment of eco- and toxicological properties by read-across on the basis of structural similarity and/or mechanistic reasoning. They are no members of the Alkyl Polyglycoside Category.