Fatty acids, C16-18, C16-18-alkyl esters

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable publication, which meets generally accepted scientific principles.

Data source

Reference

Reference Type:

publication

Title:

IntestinalHydrolysis and Lymphatic Absorption of Isopropyl Esters of Long-Chain Fatty Acids in the Rat

Author:

Savary, P. and Constantin, M.J.

Year:

1970

Bibliographic source:

Biochim. Biophys. Acta 218: 195-200

Materials and methods

Objective of study:

absorption

Principles of method if other than guideline:

The lymphatic absorption of simple examples of secondary-alcohol long-chain fatty esters (isopropyl esters) was studied with thoracic-duct fistula rats, to which the esters were orally administered.

GLP compliance:

no

Remarks:

; GLP was not compulsory at the time the study was conducted.

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

Animals A:
- Triglycerides or
- Ethyl stearate plus oleic acid or
- Ethyl stearate plus olive oil or
- Ethyl myristate plus olive oil
Animals B: Isopropyl stearate plus oleic acid

Radiolabelling:

yes

Remarks:

[9,10-3H2]-Oleic acid (Amersham) was added to the unlabeled acid

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

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: feed or gavage

Vehicle:

other: feed or olive oil

Details on exposure:

Animals A were allowed to eat freely a mixture of 90 parts (wet weight) boiled rice and 10 parts lipids; their lymphs were collected for 24-100 h.
Animals B received by gavage a known weight of lipid; their lymphs were collected only during a period which did not exceed by much the duration of the absorptive period, i.e. 5-9 h.

Duration and frequency of treatment / exposure:

Animals A: ad libitum via feed
Animals B: single treatment by gavage

Doses / concentrations

Remarks:

Doses / Concentrations:
Animals A: a mixture of 90 parts (wet weight) boiled rice and 10 parts lipids
Animals B: 180 or 450 mg of fat mixture

No. of animals per sex per dose / concentration:

no data given

Control animals:

not specified

Details on study design:

When the rats received acyl-labeled esters, the quantity of labeled fatty acid recovered in lymph lipids was determined by liquid scintillation counting (Packard counter Model 3003).
For the other animals, it was measured by the weight and chain analysis of lymph non-phospholipids (or triglycerides), as, under the experimental conditions, these chains are mostly of dietary origin.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Non-dietary chains were always present in lymph triglycerides. As the composition of the "endogenous fatty acids" in rat lymph triglycerides is known, their proportion can be evaluated. It does not exceed 20% of total chains.
When rats receive small weights of isopropyl stearate diluted in oleic acid, it can be calculated that 85-90 % of the stearic chains in lymph triglycerides are of dietary origin; this was confirmed by direct measurement of their specific radioactivity.

- Triglycerides: The administered triglyceride (almost devoid of trisaturated molecules and with all the stearic chains on external position) contained 149 stearic chains per 100 oleic chains, and it was calculated that the dietary chains in lymph triglycerides contain 137. This means that the lymphatic recovery of the "external" stearic chains from fed triglycerides was not very much smaller that that of other fatty chains.
- Ethyl stearate plus oleic acid: When rats were given orally mixtures of ethyl stearate with oleic acid, the recovery of stearic chains in lymph triglycerides was significantly lower than when they received triglycerides.
- Ethyl stearate plus olive oil: When oleic acid was replaced by triolein, the conclusions remain unchanged.
- Ethyl myristate plus olive oil: The same results were obtained when the rats received ehyl myristate instead of ethyl stearate.

In all experiments, only small quantities of ethyl esters were recovered unhydrolyzed in the lymph.
The experiments were then repeated with mixtures of isopropyl stearate and oleic acid. For 100 labeled stearic chains recovered in lymph lipids, less than 10 were in the form of isopropyl ester, which represents 2-3 % of the total lymph lipids. It can be calculated that less than 5 % of the remaining radioactivity was in lymph phospholipids; for the non-phospholipid fraction (isopropyl esters being excluded) 95 % or more of the radioactive label was in the triglycerides. Feeding the rats with acyl-labeled isopropyl oleate, gave similar results.
It is concluded that a part of the isopropyl ester was hydrolyzed in the intestine, and that the acids thus liberated were reesterified and partitioned between lymph lipids in the same manner as when they were fed in the form of triglycerides or of free fatty acids. Briefly, when they were fed in the form of isopropyl esters, the lymphatic recovery of dietary stearic chains was only 25-30 % of that of oleic acid. This is in contrast with the higher values, 90 and 60-70 % respectively, found in the other experiments (ingestion of a mixed triglyceride, or of ethyl stearate plus oleic acid).

Any other information on results incl. tables

Table 1: Composition of the chains in the triglycerides of rat thoracic duct lymph, after oral administration of the test materials:

Nature of the fatty diet	feeding technique	Composition (chains per 100 total chains)
			C 14:0	C 16:0	C 16:1	C 18:0	C 18:1	C 18:2	> C 18:2
Triglycerides	A	Feed mixture	-	2.2	trace	56.1	37.7	4.0	not determined
		Lymph triglycerides	-	5.9	trace	49.0	38.6	6.5	not determined
Ethyl stearate and oleic acid	A	Feed mixture	-	2.0	0.2	49.0	48.3	0.5	not determined
		Lymph triglycerides*	-	9.8	0.7	34.0	49.1	6.4	not determined
			-	7.4	0.7	35.6	51.8	4.5	not determined
Ethyl stearate and olive oil	A	Feed mixture	-	7.5	1.5	49.5	34.0	7.5	not determined
		Lymph triglycerides	-	10.8	1.5	35.5	43.4	8.8	not determined
Ethyl myristate and olive oil	A	Feed mixture	50.0	7.8	trace	0.3	34.6	7.3	not determined
		Lymph triglycerides**	36.0	14.8	trace	1.7	39.7	7.8	not determined
			41.4	12.4	trace	2.0	37.0	7.2	not determined
Isopropyl stearate and oleic acid	B	Feed mixture	-	0.3	0.2	45.5	53.8	0.2	0
		Lymph triglycerides***	-	4.2	0.6	16.8	60.5	4.1	2.5
			-	9.5	0.9	19.4	72.3	7.6	5.5

* = 2 separate samples of lymph, each collected during 24 h

** = 2 separate experiments

*** = 7 experiments: on the first line are reported the lower values and on the other the higher values obtained for each fatty chain; the sum of the number in each line is. of course, different from 100