Ethyl enantate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting 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:

Unnamed

Year:

1969

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The relative rate of hydrolysis by pancreatic lipase of the test item was determined in vitro.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl enantate

EC Number:

203-382-9

EC Name:

Ethyl enantate

Cas Number:

106-30-9

Molecular formula:

C9H18O2

IUPAC Name:

ethyl heptanoate

Radiolabelling:

no

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Not applicable

Administration / exposure

Route of administration:

other: not applicable; in vitro experiment

Vehicle:

other: not applicable; in vitro experiment

Details on exposure:

not applicable

Duration and frequency of treatment / exposure:

not applicable

No. of animals per sex per dose / concentration:

not applicable

Control animals:

other: not applicable

Details on study design:

STARTING MATERIAL
- Substrate: esters of primary n-alcohols containing 1-18 carbons and fatty acids containing 2-18 carbons
- Fatty acids: isolated from natural fats or purchased
- Alcohols: obtained from commercial sources
- Esters: synthesized from the fatty acids and alcohols, and purified by appropriate distillation, crystallization, and column chromatography.

ENZYME
- Preparation: lipolytic enzymes, other than lipase, from rat pancreatic juice were freeze-dried and inactivated for 1 hour
- pH: 9
- Temperature: 40°C

DIGESTION
- Mixture: 225 µmoles of substrate, 330 µmoles CaCl2, 7 µmoles free oleic acid, 17 mg histidine (final concentration 0.002 M), 3.11 g NaCl (final concentration 1 M) and 0.6 mg selectively inactivated, lyophilized rat pancreatic juice in a total volume of 55 ml
- pH: 9.0
- Temperature: 25°C

DATA EVALUATION
The activity of the enzyme preparation varied slightly from day to day. To correct this, replicate samples of methyl oleate were hydrolyzed each day. The values for the other esters were corrected to the standard value for the methyl oleate.

Statistics:

The values for the rates of hydrolysis of the esters are for the first few minutes after addition of the enzyme.
10% difference between two rates is significant.

Results and discussion

Main ADME results

Type:

metabolism

Metabolite characterisation studies

Metabolites identified:

not specified

Any other information on results incl. tables

Rat pancreatic lipase hydrolyses the test item at 1.4 µeq/min/mg enzyme.

Applicant's summary and conclusion

Conclusions:

Rat pancreatic lipase hydrolyses the test item at a fast rate. The relative hydrolysis rate of the test item by the pancreatic lipase was 1.4 µeq/min/mg enzyme.

Executive summary:

In the current study the rate of hydrolysis of the test item by rat pancreatic lipase was determined. In the study various esters of primary n-alcohols, containing 1 to 18 carbon atoms with fatty acids containing from 2 to 18 carbon atoms, were analysed. The test item - ethyl heptanoate - is one of the substrates examined in this experiment.

For the experimental conditions, the concentration of the substrate exceeded that of its solubility in water to assure an interface. The solidification point of the substrate was lower that the temperature of digestion to ensure a liquid/liquid interface.

The objective of the study was to determine the relative hydrolysis rates of esters, both short- as long-chained. Esters are hydrolyzed to an alcohol and a fatty acid. During the course of the study it was observed that the long-fatty acids had an accelerating effect on the hydrolysis, probably due to substrate orientation.

Rat pancreatic lipase hydrolyses the test item at a fast rate. The relative hydrolysis rate of the test item by the pancreatic lipase was 1.4 µeq/min/mg enzyme.