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Basic toxicokinetics

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basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific principles, well documented with accepptable restrictions

Data source

Reference Type:
The role of carboxyl-labelled acetic, propionic acid, butyric acids in liver glycogen formation
Buchanan JM., Hastings AB., Nesbett FB
Bibliographic source:
The journal of biological chemistry, pg 413-425

Materials and methods

Objective of study:
Principles of method if other than guideline:
The sodium salt of propionic acid was fed with 400 mg of glucose to insure adequate glycogen formation to white rats which had been fasted for 24 hours. The animals were placed in metabolism chambers and the expired carbon dioxide collected at half hour intervals for a 2 hour period. The animals were then sacrificed and the livers analyzed for their glycogen content and the radioactivity of the glycogen.
GLP compliance:

Test material

Details on test material:
- Test substance was sytehesized in the labs
- Name of test material (as cited in study report): sodium propionate
C-11 isotope

Test animals

other: White rat
Details on test animals and environmental conditions:
- Fasting period before study: Yes, for a period of 24 hours

Administration / exposure

Route of administration:
oral: feed
unchanged (no vehicle)
Details on exposure:
400 mg of glucose was added to the propionic acid solution
Duration and frequency of treatment / exposure:
no data
Doses / concentrations
Doses / Concentrations:
no data
No. of animals per sex per dose:
Control animals:
not specified
Details on study design:
6 measurements were performed with the same animal.
Details on dosing and sampling:
The animal was placed in the metabolism cage and the respiratory gases collected every half hour for a period of 2 hours. At the end of the 2 hour period, the animal was sacrificed and the liver glycogen isolated. After the glycogen had been dried with alcohol and then with ether, it was transferred to a small cup for radioactivity measurement in the electroscope. Since, under the conditions of these experiments, the glycogen isolation was not quantitative, glycogen determinations were carried out on the sample of glycogen actually used for radioactivity measurement. The total amount of glycogen present in the liver at the conclusion of the experiment was calculated from glycogen analysis of an aliquot of the alkaline digest of the liver. The radioactivity present in the total glycogen of the liver was estimated by multiplying the radioactivity of the sample, taken for measurement, by the ratio, mg. of total glycogen of the liver to mg. of glycogen used for radioactivit,y measurement.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
- The radioactivity expired as carbon dioxide calculated as total per cent of the amount absorbed was 54.8% for the period of 2 hours (51.5% and 55.9% were found for acetate and butyrate respectively)
- The radioactivity of the expired carbon dioxide calculated as per cent of the amount fed for each half hour and for the total period of time was 3.6% in the first 30mins, 6.4% between 0.5-1 h, 7.2% between 1-1.5h, 6.8% between 1.5-2 h, making a total of 24% of the amount fed. This demonstrates that propionic acid is metabolized extremely rapidly, and that after the first half hour the excretion of radioactively labelled CO2 is practically constant for the rest of the 2 hours. Similar trend was also seen for sodium acetate and sodium butyrate with a total excretion of 35.8% and 45.6% after 2 hours
- The average amount of carbon dioxide expired by the animals was 13.7 mM for propionate within 2 hour period. For acetate and butyrate, the values were 13.2 and 15.6 mM, respectively.

The average value of the radioactivity of glycogen expressed as per cent of the amount of radioactivity absorbed is 1.35, 1.00, and 1.25 for the acetate, propionate, and butyrate experiments respectively. By subtracting these values from the total amount of radioactivity incorporated after the feeding of each acid, one can estimate the amount of radioactivity in the glycogen arising from the radioactive fatty acids, exclusive of CO2. These values, calculated as per cent of the amount absorbed are 0.03, 3.27, and 1.13 for the acetate, propionate, and butyrate experiments respectively. It is concluded that propionic acid definitely is a glycogen precursor. Acetic acid is not and butyric acid is partly oxidized via a path other than carbonhydrate.

Applicant's summary and conclusion