Reaction products of decanoic acid and lauric acid with glycerol and polyglycerol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key 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:

Metabolism of Polyglycerol and Polyglycerol Esters

Author:

Michael WR, Coots RH

Year:

1971

Bibliographic source:

TOXICOLOGY AND APPLIED PHARMACOLOGY 20, 334-345 (1971)

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

Male, Sprague-Dawley rats (200-250 g) were fed the labeled compounds at a level of 1% in a liquid diet containing sucrose, milk solids, vitamins, salts, water, and fat as described by Coots (1964a). Each rat received by stomach tube 6-8 g of diet containing 7-14 &i of 14C. The precise amount of diet and radioactivity fed was determined for each animal. There were always 4 animals per group for each test compound.

Rats of the Sprague-Dawley strain were trained to consume the daily ration in 30 min. On the day of the experiments, instead of the daily ration, the animals were fed the experimental diet and placed immediately in individual metabolism chambers. Distribution of radioactivity among collected respiratory CO2, feces, urine, gastrointestinal tract contents, and carcass was determined for each animal at the end of the 51-hr experimental period.

Each animal was provided with a thoracic duct cannula by a procedure similar to that of Bollman et al. (1948). The day following surgery, the radioactive compound was fed. Each rat was placed immediately into an individual metabolism chamber designed for the collection of lymph, respiratory CO2, feces, and urine. Each of these was collected as a single fraction during the 51-hr experimental period and then assayed for total 14C-content.
Lipids were extracted from the lymph of animals fed fatty acid-labeled polyglycerol esters. The distribution of radioactivity among the various lipid constituents of the lymph was then obtained to determine whether any intact polyglycerol esters were present in the lymph lipids.

All the fatty acid-labeled polyglycerol esters were subjected to enzymatic digestion in vitro with fresh pancreatic juice plus bile.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

n.a.

IUPAC Name:

n.a.

Specific details on test material used for the study:

14C-labelled glycerols:
G1*
G3*
G10*
G10*-O1
G10*-O10
14C-labelled fatty acid esters:
G3-O1*
G3-O4*
G10-O1*
G10-O10*
G10-E1*

G1 = glycerol; G3 = triglycerol; G10 = polyglycerol; O = oleic acid. E = eicosanoic acid; * = 14C labeled moiety

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200-250 g

Administration / exposure

Route of administration:

other: liquid diet by gavage

Duration and frequency of treatment / exposure:

single exposure

No. of animals per sex per dose / concentration:

4

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

More than 90% of the triglycerol (G3) and approx. 40 % of the polyglycerol (G10) moieties were absorbed.

Main ADME results 2

Type:

metabolism

Results:

Hydrolysis of the esters occurred to a large extent prior to absorption.

Main ADME results 3

Type:

metabolism

Results:

Pancreatic enzymes hydrolyzed the oleate ester linkages of the triand polyglycerols as readily as they did those of natural fats. The Polyglycerols were not catabolized; the ether linkages within the molecule are inert to normal enzymatic hydrolysis.

Main ADME results 4

Type:

metabolism

Results:

The fatty acid moiety of the polyglycerol esters was absorbed and utilized as well as those of natural fats.

Metabolite characterisation studies

Metabolites identified:

not specified

Applicant's summary and conclusion

Conclusions:

Data from metabolism studies clearly show that absorption of administered radioactivity was excellent for the fatty acid-labeled polyglycerol (G10) (oleic acid > 90 %; eicosanoic acid > 77%) and triglycerol (G3-oleate) esters. More than 90% of the triglycerol (G3) and - 40 % of the polyglycerol (G10) moieties were absorbed. Hydrolysis of the esters occurred to a large extent prior to absorption; the thoracic lymph duct was the major pathway for absorption of the fatty acid moieties, while absorption of the more polar G3 and G10 moieties occurred by some other pathway, presumably the portal vein.
Pancreatic enzymes hydrolyzed the oleate ester linkages of the tri-and polyglycerols as readily as they did those of natural fats (glycerides).

In catabolism studies involving triglycerol (G3*) and polyglycerol (G10*) labeled compounds, less than 4% of the 14C was excreted in the respiratory CO2. This quantity was, within experimental limits of detection, equal to the amount of glycerol contaminant in each sample that was fed. It is concluded that the polyglycerols were not catabolized and that the ether linkages within the molecule are inert to normal enzymatic hydrolysis.
The data also suggested that, unlike glycerol, the polyglycerols (G3* and G10*) were not retained appreciably in the carcass (approx. 5 %). In summary, these results show clearly that the polyglycerols were absorbed and excreted rapidly in the urine without being catabolized.