Methylsilanetriyl triacetate

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

Remarks:

Although the study was not conducted according to the recommended guidelines, it provides scientific valid information to assess the elimination pattern of the substance.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1967

Report date:

1966

Materials and methods

Objective of study:

excretion

Principles of method if other than guideline:

Adult white rats (5 to 9 months old) of an inbred Oregon State Wistar strain were used. The aqueous solutions of sodium acetate were administered to the rats by means of a stomach tube. After the acetate-C14 was administered, the rat was placed in a Delmar metabolism cage and the CO2 was trapped by sodium hydroxide solution. The sodium hydroxide solution from the CO2 trap was changed periodically and was analyzed for radioactivity after conversion of CO2 to BaCO3. The BaCO3 was filtered onto a glass fiber disk, washed and dried and the radioactivity counted. The urine samples were collected and clarified by centrifugation at low speed. The radioactivity in the faeces was obtained by extracting the faeces with a sufficient volume of 50% ethanol. The solid materials were centrifuge out and an aliquot of the supernatant was analysed for radioactivity.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium acetate

EC Number:

204-823-8

EC Name:

Sodium acetate

Cas Number:

127-09-3

IUPAC Name:

sodium acetate

Details on test material:

- Name of test material (as cited in study report): Crystalline sodium acetate-1-C14 and -2-C14.

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Duration and frequency of treatment / exposure:

Single dose

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:

From 79 to 95% of orally administered acetate-14C was recovered in the form of 14CO2. Only a small amount of the radioactivity was found in the urine and faeces. The radioactivity recovered from excreta during the first 24-h period was considerably less from the males than from the females. Male rats apparently tend to fix more of the radioactivity in the body tissues, and the acetate carbons were not turned over as rapidly as in the females.

Any other information on results incl. tables

There are two separate rates for the elimination of ¹⁴CO₂. The initial rate of elimination (1 to 8 hours postmedication) is very rapid and has a biological half-life of 4 to 6 hours, followed by a much slower rate of elimination (half-life of about 25 hours). The appearance of two separate rates of ¹⁴CO₂elimination represents two routes of metabolism of the acetate carbons. The initial rate of elimination is probably due to the direct reaction of acetate with CoA-SH to form acetyl-CoA, which subsequently is oxidised to CO₂through the TCA cycle. In the intact animal, the CO₂would be present in the form of blood bicarbonate and as the blood bicarbonate is turned over, there is a subsequent release of CO₂from the lungs. The slower, secondary rate of elimination is probably derived from acetate carbons which are incorporate into other metabolites, such as fatty acids and amino acids and are subsequently catabolised to CO₂.

Applicant's summary and conclusion

Conclusions:

From 79 to 95% of orally administered acetate-14C was recovered in the form of 14CO2. Only a small amount of the radioactivity was found in the urine and faeces. The radioactivity recovered from excreta during the first 24-h period was considerably less from the males than from the females. Male rats apparently tend to fix more of the radioactivity in the body tissues, and the acetate carbons were not turned over as rapidly as in the females.

Executive summary:

Adult white rats (5 to 9 months old) of an inbred Oregon State Wistar strain were used. The aqueous solutions of sodium acetate were administered to the rats by means of a stomach tube. After the acetate-C¹⁴was administered, the rat was placed in a Delmar metabolism cage and the CO₂was trapped by sodium hydroxide solution. The sodium hydroxide solution from the CO₂trap was changed periodically and was analyzed for radioactivity after conversion of CO₂to BaCO₃. The BaCO₃was filtered onto a glass fiber disk, washed and dried and the radioactivity counted. The urine samples were collected and clarified by centrifugation at low speed. The radioactivity in the faeces was obtained by extracting the faeces with a sufficient volume of 50% ethanol. The solid materials were centrifuge out and an aliquot of the supernatant was analysed for radioactivity.

From 79 to 95% of orally administered acetate-¹⁴C was recovered in the form of ¹⁴CO₂. Only a small amount of the radioactivity was found in the urine and faeces. The radioactivity recovered from excreta during the first 24-h period was considerably less from the males than from the females. Male rats apparently tend to fix more of the radioactivity in the body tissues, and the acetate carbons were not turned over as rapidly as in the females.

There are two separate rates for the elimination of ¹⁴CO₂. The initial rate of elimination (1 to 8 hours postmedication) is very rapid and has a biological half-life of 4 to 6 hours, followed by a much slower rate of elimination (half-life of about 25 hours). The appearance of two separate rates of ¹⁴CO₂elimination represents two routes of metabolism of the acetate carbons. The initial rate of elimination is probably due to the direct reaction of acetate with CoA-SH to form acetyl-CoA, which subsequently is oxidised to CO₂through the TCA cycle. In the intact animal, the CO₂would be present in the form of blood bicarbonate and as the blood bicarbonate is turned over, there is a subsequent release of CO₂from the lungs. The slower, secondary rate of elimination is probably derived from acetate carbons which are incorporate into other metabolites, such as fatty acids and amino acids and are subsequently catabolised to CO₂.