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dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study
according to guideline
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
Details on test animals or test system and environmental conditions:
Skin region: abdomen
BMI: 22.7-29.1
Type of coverage:
other: HBSS-buffer
Duration of exposure:
24 h
No. of animals per group:
3 donors (n=2)
Control animals:
Details on in vitro test system (if applicable):
- Source of skin: human
- Ethical approval if human skin: yes
- Type of skin: fresh abdominal skin
- Preparative technique: skin sections were prepared from the full-thickness skin samples using an Aesculap GA 630 dermatome.
- Thickness of skin (in mm): 0.5
- Membrane integrity check: yes
- Storage conditions: full-thickness skin was stored at -20 °C.

- Diffusion cell: Franz diffusion cell
- Receptor fluid: Hank´s buffered salt solution (HBSS) without glucose, pH 6.5
- Solubility of test substance in receptor fluid: yes
- Static system: yes
- Test temperature: 32 ± 2 °C,
- Occlusion: yes. Franz diffusion cells were kept covered with Parafilm®
- Reference substance(s): caffeine
Absorption in different matrices:
The mean amount of CG removed from the skin surface (skin wash) ranged from 109.26% to 144.57% of the dose applied. The mean recovery (mean value for 6 Franz cells) in the two first tape strips was 0.52% during all performed experiments. In the further 18 tape strips a mean recovery of 0.30% was documented. The mean absorbed dose of CG, sum of the amounts found in the viable epidermis, dermis and receptor medium, were considered as 0.01%.
Total recovery:
- Total recovery: 88.65-112.28%
- Recovery of applied dose acceptable: 100 ± 20%
- Results adjusted for incomplete recovery of the applied dose:
- Limit of quantification (LOQ): 0.088 μg/mL in KRB pH 7.4 without HEPES and glucose
< 1 %
Remarks on result:
other: 24 h
The mean absorbed dose of CG, sum of the amounts found in the viable epidermis, dermis and receptor medium, were considered as 0.01%.
The mean absorbed dose of CG, sum of the amounts found in the viable epidermis, dermis and receptor medium, were considered as 0.01%.

Description of key information

Dermal absorption 0.01%, OECD TG 428, human skin, GLP, RL1

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information



Experimental in vivo data on oral, inhalative and dermal absorption, distribution and excretion is not available for the target and source substances. Therefore the toxicokinetic assessment is based on physicochemical properties and on in-vitro dermal penetration data with a similar substance (D-Glucopyranose, oligomers, decyl octyl glycosides).


Similar toxicokinetic behaviour is expected for the source substances based on structural similarity and similar physicochemical properties.



Oral absorption

There are some studies on oral absorption of alkyl glycosides available in the literature. A study investigating the distribution, metabolism and excretion of monomeric alkyl glycosides is available, in which female NMRI mice received radiolabelled octyl glucoside, dodecyl maltoside, and hexadecyl glucoside via oral gavage (Weber and Benning, 1984). Two hours after administration, the radiolabelled alkyl glycosides were mostly recovered unchanged in the stomach, while the second highest portion of radioactivity was recovered as radiolabelled metabolites in the intestine, thus suggesting intestinal absorption and metabolism.

As shown in a study with α-ethylglucoside, which differs from β-alkyl glycosides only in the configuration of the glycosidic bond, a small amount of the alkyl glycoside was hydrolysed and most of it was absorbed in intact form via the sodium-dependent glucose transporter SGLT1 and the facilitative glucose transporter GLUT2 in the rat small intestine (Mishima et al., 2005). There is also evidence from another study using hamster intestinal SGLT1 that these transporters also have affinity to β-alkyl glycosides, and that the affinity of alkyl glycosides for SGLT1 increased with increasing alkyl chain length (Ramaswamy, 1976).

Thus, it may be assumed that the high proportion of radioactivity from β-alkyl glycosides in the intestine as described in the study by Weber and Benning (1984) may be facilitated by active transport mechanisms into the small intestinal cells via glucose transporters.

Based on the strong similarity in chemical structure compared to β-alkyl glycosides, it is anticipated that alkyl polyglycosides will be readily absorbed and metabolised in the intestine after oral ingestion, as well.

For Risk-Assessment purposes the oral absorption was set to 100%.


Respiratory absorption

D-Glucose, reaction products with alcohols C16-18 (even numbered) is a solid with a low vapour pressure (between 1.0E-12 Pa and 1.0E-13 Pa at 20 °C) for the main constituents, thus being of low volatility.

For Risk-Assessment purposes the respiratory absorption was set to 100%.


Dermal Absorption

A reliable study according to OECD guideline 428 is available, investigating the dermal absorption of D-Glucopyranose, oligomers, decyl octyl glycosides (CAS 68515-73-1) in dissected abdominal human skin from three donors (Across Barriers, 2009). The test substance at a concentration of 10% in HBSS buffer was applied to the surface of the skin sample separating the two chambers of a Franz diffusion cell. After an exposure period of 24 h under occlusive conditions, the mean absorbed dose of the test substance, sum of the amounts found in the viable epidermis, dermis and receptor medium, was determined to be 0.01%. Thus, dermal absorption of D-Glucopyranose, oligomers, decyl octyl glycosides was considered to be low.


Compared with the target substance, Glucopyranose, oligomers, decyl octyl glycosides has a higher water solubility (> 200 g/L vs. 0.142 mg/L) and a lower Log Pow value (< 1.77 vs. 4.64).


It is a generally anticipated that the dermal uptake is low, if the water solubility is <1 mg/L. The dermal absorption of substances with a water solubility between 1-100 mg/l is anticipated to be low to moderate. Log Pow values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal), in particular if water solubility is high. Above Log Pow values of 4, the rate of penetration may be limited by the rate of transfer between the stratum corneum and the epidermis (ECHA, 2014).


Based on the lower water solubility and the higher Log Pow value value of the target substance, the results with Glucopyranose, oligomers, decyl octyl glycosides is considered to be a worst case. Therefore the value of 0.01 % dermal absorption is taken over for the risk assessment of D-Glucose, reaction products with alcohols C16-18 (even numbered).


Distribution, Metabolism, Elimination 

A study extensively investigating the metabolism, distribution and excretion of the structurally related monomeric β-alkyl glycosides octyl glucoside, dodecyl maltoside, and hexadecyl glucoside is available (Weber and Benning, 1984). These substances cover a broad range of possible chain lengths of non-branched fatty alcohols (C8-C16) for commercial alkyl polyglycosides (Cognis Corporation, 2007). In this study, each of the corresponding 14C-radiolabelled β-alkyl glycosides was administered once to female NMRI mice via oral gavage and the distribution of radioactivity in water-soluble and water-insoluble extracts of specific organs and tissues as well as in urine was determined 2 h after administration.

The results of this study demonstrated that the radiolabelled β-alkyl glycosides were rapidly and extensively metabolised, as a large amount of the radioactivity was found in the water-soluble extract of the urine, being indicative of a high rate of metabolic degradation of alkyl glycosides to water-soluble metabolites like carbohydrates, carboxylic acid and amino acids (Weber and Benning, 1984).

The highest level of radioactivity after treatment with the alkyl glycosides was found in the stomach of mice. Most of the radioactivity (ca. 80%) in the stomach was attributed to the unchanged alkyl glycosides, showing that the β-glycosidic bond of the radiolabelled alkyl glycosides was only hydrolysed to a minor extent. The small rate of metabolism in the stomach was further supported by the fact that hardly any water-soluble metabolites were found in the aqueous extracts of the stomach after treatment with the radiolabelled alkyl glycosides (Weber and Benning, 1984).

In contrast, a high rate of hydrolysis of the β-alkyl glycosides was found in liver, intestine and kidney, as reflected by the large amount of radioactivity found in these organs. During intestinal and liver passage, the medium-chain alcohol chains (octanol and dodecanol) of hydrolysed alkyl glycosides were rapidly transformed into hydrophilic metabolites, as reflected by a relatively high proportion of the radioactivity in the water-soluble extracts of liver and intestine. In contrast, the long-chain hexadecyl glucoside showed a much greater tendency towards lipophilic metabolism, rather resulting in the formation of glycerolipids containing radiolabelled palmitoyl moieties in liver and intestine than in the formation of β-oxidation metabolites (Weber and Benning, 1984; Cognis Corporation, 2007). These findings were supported by the fact that β-oxidation occurs faster in medium-chain fatty acids like octanoic acid than in long-chain fatty acids such as hexadecanoic acid (Scheig, 1968; Petit et al., 1982).

Due to the asymmetric substitution of the anomeric carbon atom of D-glucose, alkyl polyglycosides are stereoisomers (anomers) with α- and β-configuration of the glycosidic bond, respectively (Cognis Corporation, 2007). Generally the α-glycosidic bond is weaker than the β-glycosidic bond and can already be cleaved by α-amylases of the saliva, which is well known from the digestion of the α-glycosidic bound glucose molecules in starch (Lehninger, 1993). Further cleavage of the α-glycosidic bond also takes place by the activity of pancreatic amylases in the intestine (Lehninger, 1993). Thus, it is anticipated that alkyl polyglycosides with α-glycosidic bond may be hydrolysed in saliva and intestine, as well.

In summary, the common and crucial metabolic fate of alkyl polyglycosides involves hydrolysis of the glycosidic bond to the cleavage products fatty alcohol and glucose, respectively.

Glucose and glucose polymers enter the carbohydrate metabolic pathway, where they are either interconverted or finally catabolised to CO2 and H2O (Lehninger, 1993).

The fatty alcohols represent the main difference in the structure of the different alkyl polyglycosides, but they will mainly be metabolised to the corresponding carboxylic acid via the aldehyde as a transient intermediate (Lehninger, 1993). The stepwise process starts with the oxidation of the alcohol by alcohol dehydrogenase to the corresponding aldehyde, where the rate of oxidation increases with increasing chain-length. Subsequently, the aldehyde is oxidised to carboxylic acid, in a reaction catalysed by aldehyde dehydrogenase. Both alcohol and aldehyde may also be conjugated with e.g. glutathione and excreted directly, bypassing further metabolism steps (WHO, 1999a).

Long-chain alcohols liberated from β-alkyl glycosides may also be acylated to wax esters, incorporated into either glycerolipids or oxidised to fatty acids by alcohol and aldehyde dehydrogenase via the intermediate aldehyde (Weber and Benning, 1984).

A major metabolic pathway for linear and branched fatty acids is the β-oxidation, in which fatty acids are at first esterified into acyl-CoA derivatives and subsequently transported into cells and mitochondria by specific transport systems. In a subsequent step, the acyl-CoA derivatives are cleaved into acetyl-CoA molecules by sequential removal of 2-carbon units from the aliphatic acyl-CoA molecule. The acetyl-CoA is further oxidised via the citric acid cycle, resulting in the formation of CO2 (Lehninger, 1993).

During β-oxidation, acids with an even number of carbon atoms continue to be cleaved to acetyl-CoA, while acids with an odd number of carbon atoms yield acetyl-CoA and propionyl-CoA (WHO, 1999b). Branched-chain acids can be metabolised via the same β-oxidation pathway as linear ones, depending on the steric position of the branch, but at lower rates (WHO, 1999a). An alternative pathway for the metabolism of branched-chain fatty acids is the α-oxidation in peroxisomes, which takes place when a β-methyl branch hinders β-oxidation. In this pathway, fatty acids are shortened by a single carbon unit in a preliminary step before the removal of 2-carbon units continues (Casteels et al., 2003). Alternative pathways for long-chain fatty acids include the omega-oxidation, resulting in the formation of a primary alcohol that may undergo further oxidation to the corresponding carboxylic acid. The carboxylic acid may then enter the β-oxidation pathway or, alternatively, may be excreted via urine depending on the polarity attained (WHO, 1999b).

In summary, it is anticipated that alkyl polyglycosides are 100% absorbed by oral ingestion, followed by ready hydrolysis and metabolism of the resulting cleavage products, sugar and fatty alcohol, in common mammalian physiological pathways.




Across Barriers (2009). Testing laboratory: Across Barriers GmbH. Saarbruecken, Germany Report no.: C-10335-244-1107. Owner company: BASF Personal Care and Nutrition GmbH, Monheim, Germany. Report date: 2009-04-30.


Casteels M, Foulon V, Mannaerts GP, Van Veldhoven PP (2003). Alpha-oxidation of 3-methyl-substituted fatty acids and its thiamine dependence. Eur J Biochem. 270(8):1619-27.


Cognis Corporation (2007). GRAS EXEMPTION CLAIM Alkyl Polyglycoside Surfactants; November 28, 2007.


ECHA (2014). Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.


Lehninger, A.L., Nelson, D.L. and Cox, M.M. (1993). Principles of Biochemistry. Second Edition. Worth Publishers, Inc., New York, USA. ISBN 0-87901-500-4.


Mishima T, Tanaka K, Tsuge H, Sugita J, Nakahara M, Hayakawa T. (2005). Studies on Absorption and Hydrolysis of Ethyl α-D-Glucoside in Rat Intestine. J Agric Food Chem. 53(18):7257-61.


Petit, D., Raisonnier, A., Amit, N., Infante, R. (1982). Lack of Induction of VLDL Apoprotein Synthesis by Medium Chain Fatty Acids in the Isolated Rat Liver. Ann Nutr Metab. 26 (5):279-86


Ramaswamy, K., Bhattacharyya, B. R., Crane, R. K. (1976). Studies on the transport of aliphatic glucosides by hamster small intestine in vitro. Biochim. Biophys. Acta 433 (1):32-38.


Scheig, R. (1968). Hepatic Metabolism of Medium Chain Fatty Acids. In Medium-Chain Triglycerides; Senior, JR. Ed. University of Pennsylvania Press: Philadelphia; 39-49


Weber N. and Benning, H. (1984): Metabolism of Orally Administered Alkyl β-Glycosides in the Mouse. J Nutr. 114(2):247-54.


WHO (1999a). Evaluation of certain food additives and contaminants. Forty-ninth report of the joint FAO/WHO Expert Committee on Food Additives. WHO Technical Report Series 884. ISBN 92 4 120884 8.


WHO (1999b). Safety evaluation of certain food additives and contaminants. Linear and branched-chain aliphatic, unsaturated, unconjugated alcohols, aldehydes, acids, and related esters. WHO food additives series 42.