Hexanoic acid, 3,5,5-trimethyl-, 1,1'-[2-ethyl-2-[[(3,5,5-trimethyl-1-oxohexyl)oxy]methyl]-1,3-propanediyl] ester

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:

other: Acceptable, well-documented publication meeting basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Absorbability by Rats of Compounds Containing form One to Eight Ester Groups

Author:

Mattson, F.H. and Nolen, G.A.

Year:

1972

Bibliographic source:

The Journal of Nutrition, 102: 1171-1176.

Materials and methods

Objective of study:

absorption

Principles of method if other than guideline:

The absorbability of the fatty acid moiety of the complete, oleate esters of alcohols containing from one to six hydroxyl groups was determined by the fat balance technique in adult rats. Similarly, the absorbability of sucrose octaoleate and sucrose monooleate was determined.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

oleate esters of alcohols containing from one to six hydroxyl groups

IUPAC Name:

oleate esters of alcohols containing from one to six hydroxyl groups

Details on test material:

By a combination of urea adduction and low-temperature solvent crystallization, ethyl oleate of better than 98% purity was isolated from the ethyl esters prepared from olive oil. The alcohols used in the preparation of the esters were obtained from commercial suppliers. The purity of the oleic acid, the alcohols, and the esters was determined by thin-layer chromatography, gas-liquid chromatography, and chemical analysis. The synthesis of the esters was based on procedures we have described previously.
Methyl oleate: Ethyl oleate was transesterified with methyl alcohol using KOH as a catalyst.
Ethylene glycol dioleate: Ethylene glycol was esterified with oleic acid using toluene sulfonic acid as a catalyst.
Triolein and erythritol tetraoleate: Ethyl oleate was transesterified with dry glycerol or erythritol using sodium methoxide as the catalyst.
Pentaerythritol tetraoleate, xylitol pentaoleate, sorbitol hexaoleate, and sucrose octaoleate: The appropriate alcohol and ethyl oleate were dissolved in dimethyl acetamide and transesterified with sodium methoxide as the catalyst.
Sucrose monooleate: The procedure was the same as that for sucrose octooleate except that a large molar excess of sucrose was used.

Except in the case of the sucrose mono oleate, the reaction products were taken up in petroleum ether, washed with dilute mineral acid or alkali and then with water. Further purification was by repeated crystallization from cold acetone. The sucrose mono oleate was dissolved in 1:1 butanol : ethyl acetate and recrystallized from ethyl acetate. All of the esters were of better than 95% purity and most were greater than 98% pure.
These fats were incorporated into a semi purified diet

Radiolabelling:

no

Test animals

Species:

rat

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: no data
- Age at study initiation: young adult
- Weight at study initiation: approx. 200 g
- Housing: Individually in cages with raised screen bottoms
- Diet (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

oral: feed

Duration and frequency of treatment / exposure:

10 Days, diet ad libitum

Doses / concentrations

Remarks:

Doses / Concentrations:
10% and 25 % of dietary fat

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The fatty acids of the compounds containing less than four ester groups, methyl oleate, ethylene glycol dioleate, glycerol trioleate, and sucrose monooleate, were almost completely absorbed. As the number of ester groups was increased - erythritol and pentaerythritol tetraoleate and xylitol pentaoleate - the absorbability decreased. The fatty acids of sorbitol hexaoleate and sucrose octaoleate were not absorbed. These differences in absorbability are related to the activity and specificity of the lipolytic enzymes in the lumen of the intestinal tract.

Any other information on results incl. tables

The fatty acids of the compounds containing less than four ester groups, methyl oleate, ethylene glycol dioleate, glycerol trioleate, and sucrose monooleate, were almost completely absorbed. As the number of ester groups was increased - erythritol and pentaerythritol tetraoleate and xylitol pentaoleate - the absorbability decreased. The fatty acids of sorbitol hexaoleate and sucrose octaoleate were not absorbed. These differences in absorbability are related to the activity and specificity of the lipolytic enzymes in the lumen of the intestinal tract.

Test fat	Percentage of dietary fat	Absorbability [%]
Methyl Oleate	10	100
	25	96
Ethylen Glycol Oleate	10	100
	25	92
Glycerol Trioleate	100	(100)
Erythritol Tetraoleate	10	-
	25	72
Pentaerythritol Tetraoleate	10	90
	25	64
Xylol Pentaoleate	10	50
	25	24
Sorbitol hexaoleate	10	0
	25	0
Sucrose Octaoleate	5	0
	10	0
	15	0
Sucrose Monooleate	5	100
	10	100
	15	100

Applicant's summary and conclusion

Conclusions:

Absorption rates were between 0 an 100 %, depending on the amount of ester groups present in the substance fed. Pentaerythritole tetraoleate had an absorption rate of 90% (10% of dietary fat) and 64% (25% of dietary fat), respectively. Erythritole tetraoleate had an absorption rate of 72% (25% of dietary fat).