Triacetin

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

HANDLING OF GLYCERIDES OF ACETIC ACID BY RAT SMALL INTESTINE IN VITRO

Author:

Barry, R.J.C. et al.

Year:

1966

Bibliographic source:

J. Physiol., 185, 667-683

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

Mono-, di- and triacetins were incubated with sacs of rat everted intestine.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Triacetin

EC Number:

203-051-9

EC Name:

Triacetin

Cas Number:

102-76-1

Molecular formula:

C9H14O6

IUPAC Name:

1,3-bis(acetyloxy)propan-2-yl acetate

Details on test material:

- Name of test material (as cited in study report): Mono-, di- and triacetins
- Source: British Drug Houses
- Analytical purity: no data
- Name of radiolabelled test material: Sodium [1-14C]propionate
- Source: Radiochemical Centre, Amersham, UK

Radiolabelling:

yes

Remarks:

Sodium [1-14C]propionate

Test animals

Species:

rat

Strain:

other: Sheffield

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 230 g
- Diet: diet of rat cubes No. 86 (Oxoid, London, UK), ad libitum

Administration / exposure

Route of administration:

other: in vitro

Vehicle:

other: not applicable

Duration and frequency of treatment / exposure:

1 h at 37 ºC

Doses / concentrations

Remarks:

Doses / Concentrations:
1, 2, 5, 10, 15, 20, 30, 40, 50 and 70 mM

No. of animals per sex per dose / concentration:

not applicable

Control animals:

other: not applicable

Details on study design:

In most experiments sacs of everted intestine were used; in a few experiments homogenates were employed. In all cases the middle fifth of the combined jejunum and ileum was used, as this appears to be the most active segment of the gut in transfer of volatile fatty acids. The everted sac was used for study both of transfer and of capacity for hydrolysis, and these required different techniques.

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

This study clearly demonstrated that triacetin is hydrolysed to free glycerol (CAS No. 56-81-5) and acetic acid (Cas No. 64-19-7) by rat intestine without positional specificity for ester linkages.

Any other information on results incl. tables

The acetate released appeared in higher concentrations on the serosal side: when 100 µmoles of acetate were initially present in the mucosal fluid:

- the mucosal transfer was 38 µmoles (diminution in the volume on the mucosal side)

- the serosal transfer was 19 µmoles (increase in volume inside the sac)

- the final mucosal conc. was 4.48 mM

- the final serosal conc. was 9.96 mM

With increasing concentrations of mono-, di- and triacetin (5, 10 and 15 mM), the amount of acetate release increased linearly up to about a total amount of 300 µmoles of acetates release.

With increasing number of acetic acid residues, the amounts of released acetate increased: when mono-, di- and triacetin (15 mM) were hydrolysed 92, 206 and 307 µmmoles of acetate were released, respectively.

Extent of hydrolysis of acetins:

The rate-limiting step of acetin hydrolysis was the entry of glyceride into the epithelial cell.

Site of hydrolysis:

No hydrolytic activity could be detected in the mucosal or serosal fluids at the end of the incubation, so that this activity depends on the presence of intestinal tissue. The results indicate that the acetate is released on the 'cell' side of a diffusion barrier, and is in this sense intracellular.