Myo-inositol

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 Metabolism in the Rat of Photosynthetically Prepared Myo-Inositol-C14

Author:

Moscatelli EA and Larner J

Year:

1959

Bibliographic source:

Arch. Biochem. Biophys., 80:26-34

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The pathway of carbon in test substance biosynthesis and dissimilation along 3 pathways (oxidation to CO2; incorporation into lipides of brain, liver, kidney, and heart; and conversion to liver glycogen) in the intact, normal rat.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Myo-inositol

EC Number:

201-781-2

EC Name:

Myo-inositol

Cas Number:

87-89-8

Molecular formula:

C6H12O6

IUPAC Name:

cyclohexane-1,2,3,4,5,6-hexol

Test material form:

solid

Details on test material:

- Purity: not reported

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

not specified

Sex:

female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

not specified

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

21.6 other: mg

Remarks:

In experiment No. 1, the first dose was 897000 disintegrations/min of the carbon-14 labled test substance with a reactivity of 41500 disintergrations/mg. The dose in mg was determined by dividing 897000 by 41500 to yield 21.6 mg.

Doses / concentrations 2

Dose / conc.:

24.5 other: mg

Remarks:

In experiment No. 1, the second dose was 1015000 disintegrations/min of the carbon-14 labled test substance with a reactivity of 41500 disintergrations/mg. The dose in mg was determined by dividing 1015000 by 41500 to yield 24.5 mg.

Doses / concentrations 3

Dose / conc.:

83.3 other: mg

Remarks:

In experiment No. 2, the total dose was 2090000 disintegrations/min of the carbon-14 labled test substance with a reactivity of 25100 disintergrations/mg. The dose in mg was determined by dividing 2090000 by 25100 to yield 83.3 mg.

Doses / concentrations 4

Dose / conc.:

33.9 other: mg

Remarks:

In experiment No. 3, the total dose was 4,200,000 disintegrations/min of the carbon-14 labled test substance with a reactivity of 124,000 disintergrations/mg. The dose in mg was determined by dividing 4,200,000 by 124,000 to yield 33.9 mg.

No. of animals per sex per dose / concentration:

1

Control animals:

no

Positive control reference chemical:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:

The yields of CO2 were 25.7% for the Experiment 1 rat (starved), 22.3% for the Experiment 2 rat (starved), and 10.1% for the Experiment 3 rat (fed). Higher recoveries of CO2 were found in the starved rats. Recoveries in the urine were 22.8, 56.0, and 6.2% In Experiments 1, 2, and 3, respectively. Almost 50% of the administered radioactive dose was found in the carcass of the rat in Experiment 3; an over-all recovery of approximately 66% of the administered radioactive dose.

Applicant's summary and conclusion

Conclusions:

The test substance is metabolized to CO2 by the rat, approximately 25% of the administered dose being excreted into the respiratory CO2.

Executive summary:

Three pathways of test substance metabolism [(a) oxidation to CO₂; (b) incorporation into lipids of brain, liver, kidney, and heart; and (c) conversion to liver glycogen] in the whole rat were quantitatively investigated. A small conversion to glucose is shown by liver glycogen labeling. Comparable amounts are incorporated into organ lipids. A much larger conversion is represented by a vigorous oxidative dissimilation to CO2. The largest total incorporations were found in the lipides from liver and kidney.