D-mannose

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:

Studies of the Metabolism of Mannose

Author:

Bailey WH and JH Roe

Year:

1944

Bibliographic source:

J. Biol.Chem.,152:135-146

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The effect of mannose ingestion was investigated to determine the effect on blood sugar. Concentrations of blood mannose or glucose were followed over periods of 4-10 hours after mannose or glucose administration and total urinary excretion was measured in periods for 24 to 36 hours after the start of the experiment. Three phases of experiments were carried out on 5 different rabbits. In five of these experiments, differential glucose and mannose determinations were run on each blood sample.

Test material

Test material information

Constituent 1

Reference substance name:

D-mannose

EC Number:

222-392-4

EC Name:

D-mannose

Cas Number:

3458-28-4

Molecular formula:

C6H12O6

IUPAC Name:

D-mannose

Details on test material:

Purity: not reported

Test animals

Species:

rabbit

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

oral: gavage

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

2 other: g/kg

Doses / concentrations 2

Dose / conc.:

5 other: g/kg

Details on study design:

In first phase experiments, rabbits were fasted 36 to 48 hours and placed in metabolism cages. Control blood samples were taken and mannose was given by gavage in dosages of 2 to 5 g/kg in 10% solution in water. Blood samples were subsequently taken at 30 or 60 minute intervals for the duration of the experiment. Differential sugar determinations were conducted.

In second phase, experiments were conducted in fasted rabbits to determine effect of mannose on blood lactic acid. These animals were maintained in a state of mild sedation. A 2 to 3-hour control period was allowed before the animal received mannose in order to come to a steady state as far as blood sugar and blood lactate levels. Sugars were given in dosages of 2 g/kg and blood samples were taken at hourly intervals over periods of 3-6 hours. In some experiments mannose was administered via the i.p. route.

In third phase experiments, the effect of mannose administration on liver glycogen in fasted rabbits. Rabbits were anesthetized and operated on. After a sample was taken from the right liver lobe, the wound was closed, the sugar was given and the animals was kept in a metabolism cage for the duration of the experiment. After a period of at 6, 10, and 12 hours, the animal was anesthetized, reopened, and samples of the right and left liver lobes were taken for analysis. The animal was then sacrificed. Total sugar excretion was measured in the urines collected during the period of the experiment.

Results and discussion

Main ADME results

Type:

absorption

Results:

Mannose is fairly slowly absorbed from the gut, well utilized, and convertible to glucose in the intact rabbit.

Any other information on results incl. tables

Experiments on carbohydrate balance showed an average retention of 90% of the mannose dose when the sugar was administered orally or intraperiotenally. The results indicate a high degree of utilization of mannose by the rabbit. 

Mannose appeared in the peripheral venous blood and produced an elevation of blood glucose in all animals tested after mannose ingestion.  No fructose was found in any blood sample from animals tested during the hyperglycemia following mannose administration.

An increase in lactic acid was observed after mannose administration. These increases were similar to increases seen after glucose administration in that they paralleled increases in total blood sugar.

Amounts of liver glycogen found at 6, 10, and 12 hours after mannose administration were approximately in the same order as those found after glucose administration at the same dosage level when these sugars were given parenterally to animals previously fasted for 24 hours.

Applicant's summary and conclusion

Conclusions:

Mannose is fairly slowly absorbed from the gut, well utilized, and convertible to glucose in the intact rabbit. A possible mechanism for the metabolic conversion of mannose to glucose was suggested to be by way of lactic acid and liver glycogen.

Executive summary:

The effect of mannose ingestion was investigated to determine the effect on blood sugar. Concentrations of blood mannose or glucose were followed over periods of 4-10 hours after mannose or glucose administration and total urinary excretion was measured in periods for 24 to 36 hours after the start of the experiment. Three phases of experiments were carried out on 5 different rabbits. In five of these experiments, differential glucose and mannose determinations were run on each blood sample. Mannose is fairly slowly absorbed from the gut, well utilized, and convertible to glucose in the intact rabbit. A possible mechanism for the metabolic conversion of mannose to glucose was suggested to be by way of lactic acid and liver glycogen.