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Toxicological information

Basic toxicokinetics

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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

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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.

Applicant's summary and conclusion