Dodecanoic acid, ester with oxybis[propanediol]

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

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:

Unnamed

Year:

1971

Materials and methods

Objective of study:

absorption

distribution

excretion

Principles of method if other than guideline:

The catabolism of 14C-labelled polyglycerol ester was tested in rats.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Polyglycerol esters

IUPAC Name:

Polyglycerol esters

Details on test material:

- Name of test material (as cited in study report): 14C-labelled polyglycerol monooleate, polyglycerol monoeicosanoate, polyglycerol decaoleate, polyglycerol monooleate and polyglycerol decaoleate
- Specific activity: 100 µci/g
- Locations of the label: oleic and eicosanoic acid: carbon 1. Either the fatty acid component or the polyglycerol component was labelled.

Radiolabelling:

yes

Remarks:

14C

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
- Housing: animals were placed into metabolism chambers designed for the collection of respiratory CO2, faeces and urine.
- Individual metabolism cages: yes

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

liquid diet

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
- dosing solutions of the 14C-labelled test materials (1%) were prepared by dissolving appropriate amounts in liquid diet containing sucrose, milk, solids, vitamins, salts, water and fat (see Table 1 under "Any other information on materials and methods incl. tables").

VEHICLE
- Concentration in vehicle: 1%
- Amount of vehicle (if gavage): 6-8 g

Duration and frequency of treatment / exposure:

51 h

Doses / concentrations

Remarks:

Doses / Concentrations:
1%

No. of animals per sex per dose / concentration:

4

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, respiratory CO2, gastrointestinal content and carcass
- Time and frequency of sampling: after administration of the 14C-labelled test substances, animals were immediately placed in individual metabolism chambers for collection of urine, faeces and respiratory CO2.
- Other: Gastrointestinal contents and carcasses were collected after sacrifice and burned to CO2 prior to radioactivity assay (Coots, R. H. (1964). A comparison of the metabolism of elaidic, oleic, palmitic, and stearic acids in the rat. J. Lipid Res. 5, 468-472).

Statistics:

Mean values and standard errors were calculated.

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

polyglycerol monooleate (14C): 95%

Main ADME results 2

Type:

absorption

Results:

polyglycerol decaoleate (14C): 96%

Main ADME results 3

Type:

absorption

Results:

polyglycerol monoeicosanoate (14C): 77%

Main ADME results 4

Type:

absorption

Results:

polyglycerol (14C) monooleate: 44%

Main ADME results 5

Type:

absorption

Results:

polyglycerol (14C) decaoleate: 40%

Main ADME results 6

Type:

distribution

Results:

polyglycerol monooleate (14C): 25% in carcass

Main ADME results 7

Type:

distribution

Results:

polyglycerol decaoleate (14C): 29% in carcass

Main ADME results 8

Type:

distribution

Results:

polyglycerol monoeicosanoate (14C): 21% in carcass

Main ADME results 9

Type:

distribution

Results:

polyglycerol (14C) monooleate: 5% in carcass

Main ADME results 10

Type:

distribution

Results:

polyglycerol (14C) decaoleate: 3% in carcass

Main ADME results 11

Type:

excretion

Results:

polyglycerol monooleate (14C): (68.5, 2.2, 0.6 and 4% in CO2, urine, faeces and gastrointestinal contents, respectively)

Main ADME results 12

Type:

excretion

Results:

polyglycerol decaoleate (14C): (66, 1.7, 0.9 and 2.8% in CO2, urine, faeces and gastrointestinal contents, respectively)

Main ADME results 13

Type:

excretion

Results:

polyglycerol monoeicosanoate (14C): (55.5, 1.6, 9.9 and 12.2% in CO2, urine, faeces and gastrointestinal contents, respectively)

Main ADME results 14

Type:

excretion

Results:

polyglycerol (14C) monooleate: (2.1, 36.8, 9.5 and 46.5% in CO2, urine, faeces and gastrointestinal contents, respectively)

Main ADME results 15

Type:

excretion

Results:

polyglycerol (14C) decaoleate: (3.5, 33.5, 15.5 and 44.6% in CO2, urine, faeces and gastrointestinal contents, respectively)

Toxicokinetic / pharmacokinetic studies

Details on absorption:

A high absorption of administered radioactivity was observed for the fatty acid-labelled polyglycerol esters. The absorption rates were > 95% and 77% for oleic acid- or eicosanoic acid moieties, respectively (see Table 2 under “Any other information on results incl. tables”).
In contrast, based on the recovery of radioactivity from 14C-labelled polyglycerol moieties of the mono- and decaoleate esters, absorption for the polyglycerol moiety was only about 40%.

Details on distribution in tissues:

A detailed investigation on the distribution of the 14C-labelled polyglycol esters in specific organs and tissues was not performed.
In body carcass, a considerable storage of 14C-labelleled fatty acids from the polyglycerol esters was observed (> 20%). This is in line with the reported storage of long-chain fatty acids in the body fat (Coots, R. H. (1964). A comparison of the metabolism of elaidic, oleic, palmitic, and stearic acids in the rat. J. Lipid Res. 5, 468-472).
The low absorption and high excretion of 14C-labelled polyglycerol moieties corresponded to a poor retention in the body carcass (< 5%) (see Table 2 under “Any other information on results incl. tables”).

Details on excretion:

Polymerised glycerols were primarily and rapidly excreted via urine (≥ 40%) and were exreted via faeces to a smaller extent (10-15%). Via the respiratory CO2, less than 4% of the 14C was excreted, whereas ≥ 66% of the radioactivity from labelled oleic acid and ≥ 55% from labelled eicosanoic acid moieties of polyglycerol ester appeared in the respiratory CO2. The excretion of these radiolabelled moieties in urine and faeces was rather low (see Table 2 under “Any other information on results incl. tables”).

Any other information on results incl. tables

Table 2. Disposition of 14C by the rat after administration of 14C-labelled polyglycerol esters.

	Recovered radioactivity [%]
14C-labelled compound^a	CO2	Urine	Faeces	Gastrointestinal contents	Carcass
14C-labelled polyglycerol
G10*-O1	2.1 ± 0.1	36.8 ± 4.6	9.5 ± 7.1	46.5 ± 11.1	5.3 ± 3.5
G10*-O10	3.5 ± 0.0	33.5 ± 1.9	15.5 ± 8.7	44.6 ± 7.4	3.0 ± 0.3
14C-labelled fatty acid esters of glycerol
G10-O1*	68.5 ± 1.6	2.2 ± 0.7	0.6 ± 0.4	4.0 ± 0.8	24.7 ± 3.9
G10-O10*	66.0 ± 3.9	1.7 ± 0.3	0.9 ± 0.3	2.8 ± 2.1	28.7 ± 3.8
G10-E1*	55.5 ± 4.1	1.6 ± 0.3	9.9 ± 4.7	12.2 ± 4.7	20.8 ± 1.7

(N = 4 rats per group; mean values ± SEM)

^aG₁₀= polyglycerol; O = oleic acid; E = eicosanoic acid; * = 14C-labelled moiety