Xylitol

Basic toxicokinetics

Administrative data

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

Data source

Reference

Reference Type:

publication

Title:

The effects of sugar alcohols on metabolism of growing pigs

Author:

Nasi, M. & Tanhuanpaa, E.

Year:

1981

Bibliographic source:

Acta Vet. Scand., 22, 344-354

Materials and methods

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

Test material

Test material information

Constituent 1

Reference substance name:

Xylitol

EC Number:

201-788-0

EC Name:

Xylitol

Cas Number:

87-99-0

Molecular formula:

C5H12O5

IUPAC Name:

(2R,3r,4S)-pentane-1,2,3,4,5-pentol

Details on test material:

- Purity: not reported

Radiolabelling:

no

Test animals

Species:

pig

Strain:

other: Landrace

Sex:

male

Administration / exposure

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.

Doses / concentrations

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

Results and discussion

Toxicokinetic / pharmacokinetic studies

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.

Metabolite characterisation studies

Metabolites identified:

not specified

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.