Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Referenceopen allclose all

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Objective of study:
toxicokinetics
Principles of method if other than guideline:
Pigs were fed with test substance in the diet. Blood, urine and faeces were examined.
GLP compliance:
no
Radiolabelling:
no
Species:
pig
Strain:
other: Landrace
Sex:
male
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Duration and frequency of treatment / exposure:
Six male castrated pigs (39-75 kg weight range) were subjected to feeding trials based on a Latin square design with either a polyol mixture (a by-product of xylitol production containing xylane) or xylitol supplementations. The transition period between diets was five days, preliminary period seven days, and collection period seven days (seven days feeding per diet). The basic diet consisted of skim milk powder with minerals and vitamins, to which polyol mixture (levels of 5 or 2.5% dry matter) or xylitol (2.5 or 5% dry matter) were added.
Remarks:
The basic diet consisted of skim milk powder with minerals and vitamins, to which polyol mixture (levels of 5 or 2.5% dry matter) or xylitol (2.5 or 5% dry matter) were added.
No. of animals per sex per dose / concentration:
6
Control animals:
yes
Details on absorption:
There was a significant rise in plasma glucose levels in xylitol fed pigs. Urine N decreased slightly in polyol or xylitol fed animals. Albumin concentration was significantly raised. There were increases in plasma alanine and aspartate transferases (transaminases) (ALAT and ASAT also called serum glutamic pyruvic and glutamic-oxaloacetic transaminases (SGPT and SGOT)). The ALAT and SGPT levels increased significantly in a dose- related manner and indicated possible liver toxicity. Only the high dose level was statistically significantly different from the control.
Details on excretion:
There was no detectable xylitol or sugar alcohol in the faeces; a small quantity of xylitol was found in the urine of pigs when fed polyol mixture but not when fed xylitol.
Metabolites identified:
not specified

There was a slight decrease in the nitrogen balance of diets supplemented with 10% of polyol mixture or 5% of xylitol. There were increases in insulin concentrations following xylitol feeding, and values two hours after feeding were higher than control levels. This increase was also dose-related. The peak of insulin levels were between 40-60 minutes after feeding.

Conclusions:
The ALAT and SGPT levels increased significantly in a dose-related manner and indicated possible liver toxicity. Only the high dose level was statistically significantly different from the control.
Executive summary:

Pigs were fed with test substance in the diet. Faeces and urine were collected twice a day and frozen until analysed. Venous blood samples were obtained one, two, or four hours after feeding. Glucose, plasma insulin and various clinical chemical parameters were determined.

There was a slight decrease in the nitrogen balance of diets supplemented with 10% of polyol mixture or 5% of xylitol. There was no detectable xylitol or sugar alcohol in the faeces; a small quantity of xylitol was found in the urine of pigs when fed polyol mixture but not when fed xylitol. There was a significant rise in plasma glucose levels in xylitol fed pigs. Urine N decreased slightly in polyol or xylitol fed animals. Albumin concentration was significantly raised. There were increases in plasma alanine and aspartate transferases (transaminases) (ALAT and ASAT also called serum glutamic pyruvic and glutamic-oxaloacetic transaminases (SGPT and SGOT)). The ALAT and SGPT levels increased significantly in a dose- related manner and indicated possible liver toxicity. Only the high dose level was statistically significantly different from the control. There were increases in insulin concentrations following xylitol feeding, and values two hours after feeding were higher than control levels. This increase was also dose-related. The peak of insulin levels was between 40-60 minutes after feeding.

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Objective of study:
toxicokinetics
Principles of method if other than guideline:
Study conducted as PhD thesis. Rats were fed radio-labelled test substance then levels in blood were examined.
GLP compliance:
no
Radiolabelling:
yes
Species:
rat
Strain:
Wistar
Sex:
not specified
Route of administration:
oral: gavage
Vehicle:
not specified
Duration and frequency of treatment / exposure:
Sixty Wistar albino rats were gradually adapted to 20% dietary xylitol. Fully adapted and control rats were fasted overnight and dosed by oral intubation with 5 μCi of U-14C xylitol. The isotope dose was mixed with corresponding ("cold") material to obtain a final dose of 0.625 g/kg bw.
Dose / conc.:
625 mg/kg bw (total dose)
No. of animals per sex per dose / concentration:
60
Control animals:
yes
Details on distribution in tissues:
There was a significant increase in peak xylitol blood levels as determined by radioactivity in xylitol adapted rats as compared to controls.
Metabolites identified:
not measured

Xylitol adapted rats did not exhibit diarrhoea following the dose administration.

Conclusions:
Xylitol adapted rats did not exhibit diarrhoea following the dose administration. There was a significant increase in peak xylitol blood levels as determined by radioactivity in xylitol adapted rats as compared to controls.
Executive summary:

Sixty Wistar albino rats were gradually adapted to 20% dietary xylitol. Fully adapted and control rats were fasted overnight and dosed by oral intubation with 5 μCi of U-14C xylitol. The isotope dose was mixed with corresponding ("cold") material to obtain a final dose of 0.625 g/kg bw.

Xylitol adapted rats did not exhibit diarrhoea following the dose administration. There was a significant increase in peak xylitol blood levels as determined by radioactivity in xylitol adapted rats as compared to controls.

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Objective of study:
absorption
metabolism
Principles of method if other than guideline:
Summary of absorption and metabolism of xylitol.
GLP compliance:
no
Details on absorption:
Xylitol is not readily absorbed from the small intestines. Xylitol is sequestered upon entering the hepatic metabolic system and it is then further metabolised via the pentose phosphate pathway.

Absorption of xylitol from the small intestine occurs less readily than the smaller molecule erythritol, causing more to be fermented in the large bowel. Estimates of the extent of fermentation range from 50 to 75% (Livesey, 1992; Life Sciences Research Office, 1994) with the lower value being more consistent with the size of this molecule. Thus, based on D-arabitol as a non-metabolisable marker of pentitol absorption, a similar absorption of oral xylitol in man would suggest it to be 53% (Bär, 1990). This is corroborated by the present author who has predicted its absorption based on molecular weight for a series of polyols (glycerol, erythritol, mannitol and lactitol) to be 48% (see Livesey, 1992). On the basis of energy values for xylitol proposed by several experts and authorities, absorbability by consensus is 49%; this being the average of values estimated by the Dutch Nutrition Council (1987), Bär (1990), Bernier & Pascal (1990), Livesey (1992); Life Sciences Research Office (1994), and Brooks (1995). The liver readily sequesters absorbed xylitol where it is dehydrogenated by a non-specific cytoplasmic NAD-dependent dehydrogenase (synonyms iditol dehydrogenase; polyol dehydrogenase). The xylulose so produced is phosphorylated via a specific xylulokinase to xylulose-5-phosphate, an intermediate of the pentose-phosphate pathway before conversion to glucose, which is only slowly released into the blood stream or stored as glycogen (Keller & Froesch, 1972).

 

References:

Livesey G (1992) Energy values of dietary fibre and sugar alcohols for man. Nutrition Research Reviews5, 61–84.

Life Sciences Research Office (1994) The Evaluation of the Energy of Certain Sugar Alcohols Used as Food Ingredients. Bethesda, MD: Life Sciences Research Office, Federation of American Societies for Experimental Biology.

Bär A (1990) Factorial calculation model for the estimation of the physiological caloric value of polyols. In Caloric Evaluation of Carbohydrates, pp.209–257 [N Hosoya, editor]. Tokyo:Research Foundation for Sugar Metabolism.

Dutch Nutrition Council (1987) The Energy Values of Polyols. Recommendations of the Committee on Polyols. The Hague:Nutrition Council.

Bernier JJ and Pascal G (1990) The energy value of polyols (sugar alcohols).Medicine et Nutrition, 26, 221–238.

Brooks SPJ (1995) Report on the Energy Value of Sugar Alcohols. Ottawa, Canada: Ministry of Health.

Keller U and Froesch ER (1972) Vergleichende Untersuchungenüber den Stoffwechsel von Xylit, Sorbit und Fruktose beim Menschen (Comparative investigations on the metabolism of xylitol, sorbitol and fructose in humans).Schweizerische Medizinische Wochenschrift, 102, 1017–1022.

Conclusions:
Xylitol is not readily absorbed from the small intestines. Xylitol is sequestered upon entering the hepatic metabolic system and it is then further metabolised via the pentose phosphate pathway.
Executive summary:

Xylitol is not readily absorbed from the small intestines. Xylitol is sequestered upon entering the hepatic metabolic system and it is then further metabolised via the pentose phosphate pathway.

Description of key information

As demonstrated in several species (including clinical studies in humans) xylitol is slowly absorbed from the digestive tract. 25%-50% is absorbed from the small intestine depending, among others, on the dose of ingestion. Xylitol is sequestered upon entering the hepatic metabolic system and it is then further metabolised via the pentose phosphate shunt whereby fructose-6-phosphate and triose-phosphate as well as ribose-5-phosphate are yielded. The latter are important substrates for ribonucleotide biosynthesis. Portions of xylitol which are not absorbed pass to the distal parts of the gut where they are fermented to short chain fatty acids and small amounts of gas. Clinical studies in humans who had ingested xylitol for 4.3-5.3 years showed no abnormal urinary parameters or blood pressure associated with adrenal changes.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information